MIEMCAL 
 
 Gift of 
 Robert S. Stone, M.D. 
 
TEXT-BOOK OF 
 
 EMBRYOLOGY 
 
 BY 
 
 FREDERICK RANDOLPH BAILEY, A. M., M. D. 
 
 FORMERLY ADJUNCT PROFESSOR OF HISTOLOGY AND EMBRYOLOGY, COLLEGE OF PHYSICIANS AND 
 
 SURGEONS (MEDICAL DEPARTMENT OF COLUMBIA UNIVERSITY) 
 
 AXD 
 
 ADAM MARION MILLER, A. M. 
 
 PROFESSOR OF ANATOMY, LONG ISLAND COLLEGE HOSPITAL 
 AND AFFILIATED INSTITUTIONS 
 
 WITH 
 FIVE HUNDRED AND FIFTEEN ILLUSTRATIONS 
 
 NEW YORK 
 
 WILLIAM WOOD AND COMPAJSTY 
 MDCCCCXVIII 
 
COPYRIGHT, 1916, 
 BY WILLIAM WOOD & COMPANY. 
 
PREFACE TO THE THIRD EDITION 
 
 In the present edition the general plan of the book, as outlined in the 
 preface to the first edition, remains unchanged with the exception that 
 Practical Suggestions at the end of each chapter and the Appendix dealing 
 with general technic are omitted. Certain changes have been made in the 
 text and illustrations. Several chapters have been rewritten in the light of 
 recent studies, numerous changes have been made throughout the book in 
 view of the advances made in the science, and a number of new illustrations 
 supplant the old. 
 
 The writers wish to thank Mr. Adolph Elwyn for the revision of the. 
 chapters on Maturation and Fertilization. 
 
 THE AUTHORS. 
 JULY 24, 1916. 
 
 iii 
 
 81530 
 
PREFACE TO THE FIRST EDITION 
 
 The Text-book, as originally planned, is an outgrowth of the course in 
 Embryology given at the Medical Department of Columbia University. It was 
 intended primarily to present to the student of medicine the most important 
 facts of development, at the same time emphasizing those features which 
 bear directly upon other branches of medicine. As the work took form, it 
 seemed best to broaden its scope and make it of greater value to the general 
 student of embryology and allied sciences. With the opinion that illustrations 
 convey a much clearer conception of structural features than verbal description, 
 alone, the writers have made free use of figures. 
 
 The plan of adding brief "Practical Suggestions" at the end of each chapter 
 has been so thoroughly satisfactory in the Text-book of Histology, especially 
 in connection with laboratory work, that it has been adopted here. These 
 "suggestions" are not intended to be complete descriptions of embryological 
 technic, but are for the purpose of furnishing the laboratory worker with cer- 
 tain of the more essential practical hints for studying the structures described 
 in the chapter. To avoid frequent repetition, some of the best methods of 
 procuring, handling, and preparing embryological material, and some of the 
 more important formulae are given in the Appendix, which is intended to be 
 used mainly for the carrying out of the "Practical Suggestions." 
 
 The development of the Germ Layers has been treated rather elaborately 
 from a comparative standpoint, because this has been found the most satisfac- 
 tory method of teaching the subject. 
 
 In the chapter on the Nervous System the aim has been to give a general 
 conception of the subject, which, if once mastered by the student, will give 
 him an insight into the structure and significance of the nervous system that 
 will bring this difficult subject more fully within his grasp. 
 
 In Part II (Organogenesis) , at the end of each chapter there is given a brief 
 description of certain developmental anomalies which may occur in connection 
 
VI 
 
 PREFACE. 
 
 with the organs described in the chapter. In Chapter XIX (Teratogenesis) 
 the nature and origin of the more complex anomalies and monsters are dis- 
 cussed, and also the causes underlying the origin of malformations. 
 
 The writers wish to thank Dr. Oliver S. Strong for his painstaking work on 
 the chapter on the Nervous System. Dr. Strong in turn wishes to acknowledge 
 his indebtedness to Dr. Adolf Meyer for important ideas underlying the treat- 
 ment of his subject, and also for many valuable details. He expresses his 
 thanks also to Professors C. J. Herrick, H. von W. Schulte and G. L. Streeter 
 for helpful criticisms and suggestions. The writers would also express their 
 thanks to Dr. H. McE. Knower for helpful criticisms on Part I and the 
 chapter on Teratogenesis; to Dr. Edward Learning for making the photo- 
 graphs reproduced in the text; to the American Journal of Anatomy for the 
 loan of plates; and to Messrs. William Wood & Company for their uniform 
 courtesy and kindness. 
 
 FREDERICK RANDOLPH BAILEY. 
 APRIL i, 1909. ADAM MARION MILLER. 
 
CONTENTS 
 
 PART I.-GENERAL DEVELOPMENT 
 
 CHAPTER I 
 
 THE CELL AND CELL PROLIFERATION i 
 
 The Cell . i 
 
 Cell Division 3 
 
 Amitosis . 3 
 
 Mitosis 4 
 
 References for Further Study 9 
 
 CHAPTER II 
 
 THE GERM CELLS OVTJM AND SPERMATOZOON 10 
 
 The Ovum i o 
 
 The Spermatozoon 13 
 
 References for Further Study 15 
 
 CHAPTER III 
 
 MATURATION 17 
 
 Spermatogenesis Maturation of the Sperm 17 
 
 Maturation of the Ovum 21 
 
 Significance of Mitosis and Maturation 25 
 
 Sex Determination 27 
 
 Ovulation and Menstruation 29 
 
 References for Further Study 32 
 
 CHAPTER IV 
 
 FERTILIZATION 33 
 
 Significance of Fertilization 38 
 
 References for Further Study 39 
 
 CHAPTER V 
 
 CLEAVAGE (SEGMENTATION) 40 
 
 Forms of Cleavage 40 
 
 Holoblastic Cleavage 41 
 
 Equal 41 
 
 Unequal 42 
 
 vii 
 
Viii CONTENTS 
 
 Meroblastic Cleavage 44 
 
 Superficial 44 
 
 Discoidal 45 
 
 References for Further Study 50 
 
 CHAPTER VI 
 
 GERM LAYERS 51 
 
 The Two Primary Germ Layers Formation of the Gastrula 51 
 
 Gastrulation in Amphioxus 51 
 
 Gastrulation in Amphibians 52 
 
 Gastrulation in Reptiles and Birds 57 
 
 Gastrulation in Mammals 63 
 
 Formation of the Middle Germ Layer Mesoderm 68 
 
 Mesoderm Formation in Amphioxus 68 
 
 Mesoderm Formation in Amphibians 72 
 
 Mesoderm Formation in Reptiles and Birds 74 
 
 Mesoderm Formation in Mammals 81 
 
 The Germ Layers in Man . 85 
 
 References for Further Study 92 
 
 CHAPTER VII 
 
 FCETAL MEMBRANES 95 
 
 Foetal Membranes in Birds and Reptiles 95 
 
 The Amnion 95 
 
 The Yolk Sac 99 
 
 The Allantois . 102 
 
 The Chorion or Serosa 103 
 
 Foetal Membranes in Mammals 103 
 
 Amnion, Chorion, Yolk Sac, Allantois, Umbilical Cord 104 
 
 Further Development of the Chorion. 107 
 
 The Fcetal Membranes in Man in 
 
 The Amnion m 
 
 The Yolk Sac 113 
 
 The Allantois 114 
 
 The Chorion and Decidua 115 
 
 The Decidua Parietalis 119 
 
 The Decidua Capsularis 119 
 
 The Decidua Basalis 120 
 
 The Umbilical Cord 128 
 
 The Expulsion of the Placenta and Membranes 130 
 
 Anomalies !3o 
 
 References for Further Study 131 
 
CONTENTS ix 
 
 CHAPTER VIII 
 
 THE DEVELOPMENT OF THE EXTERNAL FORM OF THE BODY 133 
 
 Branchial Arches Face Neck 145 
 
 The Extremities 149 
 
 Age and Length of Embryos 151 
 
 Normal, Abnormal and Pathological Embryos 154 
 
 References for Further Study 155 
 
 PART II.-ORGANOGENESIS 
 
 CHAPTER IX 
 
 THE DEVELOPMENT OF CONNECTIVE TISSUES AND THE SKELETAL SYSTEM . . 161 
 
 Histogenesis 163 
 
 Fibers and Fibrils 166 
 
 Adipose Tissue 167 
 
 Cartilage 168 
 
 Osseous Tissue 169 
 
 Intramembranous Ossification 169 
 
 Intracartilaginous Ossification ' 172 
 
 The Development of the Skeletal System 178 
 
 The Axial Skeleton 178 
 
 The Notochord 178 
 
 The Vertebrae 179 
 
 The Ribs 184 
 
 The Sternum 185 
 
 The Head Skeleton 186 
 
 Ossification of the Chondrocranium 190 
 
 Membrane Bones of the Skull 192 
 
 Bones Derived from the Branchial Arches 194 
 
 The Appendicular Skeleton 198 
 
 Development of Joints 205 
 
 Anomalies 209 
 
 References for Further Study 213 
 
 CHAPTER X 
 
 THE DEVELOPMENT OF THE VASCULAR SYSTEM 216 
 
 The Blood Vascular System 216 
 
 Principles of Vasculogenesis 224 
 
 The Heart 227 
 
 The Septa 233 
 
 The Valves 236 
 
 Changes after Birth 237 
 
 The Arteries 240 
 
 The Veins 250 
 
X CONTENTS 
 
 Histogenesis of the Blood Cells. . . .' 267 
 
 The Lymph Vascular System 273 
 
 The Lymph Glands 280 
 
 The Spleen 283 
 
 Glomus Coccygeum 285 
 
 Anomalies 285 
 
 References for Further Study 290 
 
 CHAPTER XI 
 
 THE DEVELOPMENT OF THE MUSCULAR SYSTEM 293 
 
 The Skeletal Musculature 293 
 
 Muscles of the Trunk 295 
 
 Muscles of the Head 300 
 
 Muscles of the Extremities 303 
 
 Histogenesis of Striated Voluntary Muscle Tissue 307 
 
 The Visceral Musculature 311 
 
 Histogenesis of Heart Muscle 311 
 
 Histogenesis of Smooth Muscle 312 
 
 Anomalies 313 
 
 References for Further Study 314 
 
 CHAPTER XII 
 
 THE DEVELOPMENT OF THE ALIMENTARY TUBE AND APPENDED ORGANS . .311 
 
 The Mouth 317 
 
 The Tongue 320 
 
 The Teeth 322 
 
 The Salivary Glands 327 
 
 The Pharynx 329 
 
 The Branchial Epithelial Bodies 331 
 
 The (Esophagus and Stomach 335 
 
 The Intestine 337 
 
 Histogenesis of the Gastrointestinal Tract 342 
 
 The Development of the Liver 345 
 
 Histogenesis of the Liver 349 
 
 The Development of the Pancreas 350 
 
 Histogenesis of the Pancreas 353 
 
 Anomalies 354 
 
 References for Further Study 358 
 
 CHAPTER XIII 
 
 THE DEVELOPMENT OF THE RESPIRATORY SYSTEM 360 
 
 The Larynx 361 
 
 The Trachea 363 
 
CONTENTS XI 
 
 The Lungs 364 
 
 Changes in the Lungs at Birth . 367 
 
 Anomalies 368 
 
 References for Further Study 369 
 
 CHAPTER XIV 
 
 THE DEVELOPMENT OF THE CCELOM, THE PERICARDIUM, PLEUROPERITONEUM, 
 
 DIAPHRAGM AND MESENTERIES 370 
 
 The Pericardial Cavity, Pleural Cavities and Diaphragm 371 
 
 The Pericardium and Pleura 378 
 
 The Omentum and Mesentery 378 
 
 The Greater Omentum and Omental Bursa 378 
 
 The Lesser Omentum 379 
 
 The Mesenteries 380 
 
 The Peritoneum 382 
 
 Anomalies 382 
 
 References for Further Study 383 
 
 CHAPTER XV 
 
 THE DEVELOPMENT OF THE UROGENITAL SYSTEM 384 
 
 The Pronephros 384 
 
 The Mesonephros 386 
 
 The Kidney (Metanephros) 391 
 
 The Ureter, Renal Pelvis, and Straight Renal Tubules 391 
 
 The Convoluted Renal Tubules and Glomeruli 393 
 
 The Renal Pyramids and Renal Columns 397 
 
 Changes in the Position of the Kidneys 399 
 
 The Urinary Bladder, Urethra, and Urogenital Sinus 400 
 
 The Genital Glands 403 
 
 The Germinal Epithelium and Genital Ridge 403 
 
 Differentiation of the Genital Glands 405 
 
 The Ovary 406 
 
 The Testicle 411 
 
 Determination of Sex 412 
 
 The Ducts of the Genital Glands and the Atrophy of the Meso- 
 
 nephroi 413 
 
 In the Female 413 
 
 Oviduct 414 
 
 Uterus and Vagina 415 
 
 In the Male 416 
 
 Changes hi the Positions of the Genital Glands and the Development 
 
 of their Ligaments 417 
 
 Descent of the Testicles 419 
 
 Descent of the Ovaries 422 
 
Xll CONTENTS 
 
 The External Genital Organs 423 
 
 The Development of the Suprarenal Glands 426 
 
 The Cortical Substance 427 
 
 The Medullary Substance 427 
 
 Anomalies 429 
 
 References for Further Study 435 
 
 CHAPTER XVI 
 
 THE DEVELOPMENT OF THE INTEGUMENTARY SYSTEM 437 
 
 The Skin 437 
 
 The Nails 439 
 
 The Hair ,, 440 
 
 The Glands of the Skin 442 
 
 The Mammary Glands 442 
 
 Anomalies 444 
 
 References for Further Study 446 
 
 CHAPTER XVII 
 
 THE NERVOUS SYSTEM 447 
 
 General Considerations 447 
 
 General Plan of the Vertebrate Nervous System 450 
 
 Spinal Cord and Nerves 457 
 
 The Epichordal Segmental Brain and Nerves 459 
 
 The Cerebellum 466 
 
 The Mid-Brain Roof 467 
 
 The Prosencephalon 467 
 
 General Development of the Human Nervous System During the First 
 
 Month 472 
 
 Histogenesis of the Nervous System 478 
 
 Epithelial Stage Cell Proliferation 479 
 
 Early Differentiation of the Nerve Elements 483 
 
 Differentiation of the Peripheral Neurones of the Cord andj Epi- 
 chordal Segmental Brain 486 
 
 Efferent Peripheral Neurones 486 
 
 Afferent Peripheral and Sympathetic Neurones 489 
 
 Development of the Lower (Intersegmental) Intermediate Neurones. 502 
 
 Further Differentiation of the Neural Tube . . . . . . . 506 
 
 The Spinal Cord 506 
 
 The Epichordal Segmental Brain ..512 
 
 The Cerebellum 525 
 
 Corpora Quadrigemina 530 
 
 The Diencephalon 53! 
 
CONTENTS Xlll 
 
 The Telencephalon (Rhinencephalon, Corpora Striata and Pallium) . 538 
 
 Rhinencephalon 540 
 
 Corpora Striata and Pallium 541 
 
 The Archipallium 546 
 
 The Neopallium 552 
 
 Anomalies 560 
 
 References for Further Study 561 
 
 CHAPTER XVIII 
 
 THE ORGANS OF SPECIAL SENSE 563 
 
 The Eye 563 
 
 The Lens 565 
 
 The Optic Cup 569 
 
 The Retina 570 
 
 The Chorioid and Sclera 575 
 
 The Vitreous 575 
 
 The Optic Nerve 576 
 
 The Ciliary Body, Iris, Cornea, Anterior Chamber 577 
 
 The Eyelids 578 
 
 The Nose . 579 
 
 The Ear 582 
 
 The Inner Ear 582 
 
 The Acoustic Nerve 588 
 
 The Middle Ear 589 
 
 The Outer Ear 590 
 
 Anomalies 591 
 
 References for Further Study 592 
 
 CHAPTER XIX 
 
 TERATOGENESIS 593 
 
 Malformations Involving More Than One Individual 593 
 
 Classification, Description, Origin 593 
 
 Symmetrical Duplicity 594 
 
 Origin of Symmetrical Duplicity 599 
 
 Asymmetrical Duplicity 600 
 
 Origin of Asymmetrical (Parasitic) Duplicity 602 
 
 Malformations Involving One Individual 604 
 
 Description, Origin 604 
 
 Defects in the Region of Neural tube 604 
 
 Origin of Malformations in the Region of Neural Tube .... 607 
 
 Defects in Regions of the Face and Neck, and their Origin . . 608 
 
 Defects in the Thoracic and Abdominal Regions, and their Origin 610 
 
XIV CONTENTS 
 
 Causes Underlying the Origin of Monsters 612 
 
 The Production of Duplicate (Polysomatous) Monsters 613 
 
 The Production of Monsters in Single Embryos 614 
 
 The Significance of the Foregoing in Explaining the Production of 
 
 Human Monsters 615 
 
 References for Further Study 615 
 
INTRODUCTION 
 
 While Embryology as a science is of comparatively recent date, recorded 
 observations upon the development of the foetus date back as far as 1600 when 
 Fabricius ab Aquapendente published an article entitled "De Formato Fcetu." 
 Four years later the same author added some further observations under the 
 title, " De Formatione Foetus.' 1 Harvey (1651), using a simple lens, studied and 
 described the chick embryo of two days' incubation. Harvey's idea was that 
 the ovum consisted of fluid in which the embryo appeared by spontaneous 
 generation. Regnier de Graaf (1677) described the ovarian follicle (Graafian 
 follicle), and in the same year was announced the discovery by Von Loewenhoek 
 of the spermatozoon. These and other embryologists of this period held what 
 is now known as the prejormation theory. According to this theory, the adult 
 form exists in miniature in the egg or germ, development being merely an 
 enlarging and unfolding of preformed parts. With the discovery of the 
 spermatozoon the " pref ormationists " were divided into two schools, one hold- 
 ing that the ovum was the container of the miniature individual (ovists), the 
 other according this function to the spermatozoon (animalculists). According 
 to the ovists, the ovum needed merely the stimulation of the spermatozoon to 
 cause its contained individual to undergo development, whereas the animalcu- 
 lists looked upon the spermatozoon as the essential embryo-container, the ovum 
 serving merely as a suitable food-supply or growing-place. 
 
 Nearly a hundred years of almost no further progress in embryological 
 knowledge came to a close with the publication of Wolff's important article, 
 "Theoria Generationis," in 1759. Wolff's theory was theory pure and simple, 
 with very little basis on then known facts, but it was significant as being ap- 
 parently the first clear statement of the doctrine of epigenesis. The two es- 
 sential points in Wolff's theory were: (i) that the embryo was not preformed; 
 that is, did not exist in miniature in the germ, but developed from a more or less 
 unformed germ substance; (2) that union of male and female substances was 
 necessary to initiate development. The details of Wolff's theory were wrong 
 in that he looked upon the ovum as a structureless substance and upon the 
 seminal fluid and not upon the spermatozoon as the male fecundative agent. 
 Dollinger and his two pupils, von Baer and Pander, were the next to make 
 important contributions to Embryology. Von Baer's publication in 1829 was 
 of extreme significance in the development of embryological knowledge, for 
 
 XV 
 
xvi INTRODUCTION. 
 
 in it we have the first definite description of the primary germ layers as well as 
 the first accurate differentiation between the Graafian follicle and the ovum. 
 It will be remembered that the cell was not as yet recognized as the unit of 
 organic structure. Only comparatively gross Embryology was thus possible. 
 With the recognition of the cell as the basis of animal structure (Schleiden and 
 Schwann, 1839) the entire field of histogenesis was opened to the embryologist; 
 the ovum became known as a typical cell, while a little later (Kolliker, Reichert 
 and others, about 1840) was established the function of the spermatozoon 
 and the fact that it also was a modified cell structure. From this time we 
 may consider the two fundamental facts of Histology and of Embryology, 
 respectively, as firmly fixed beyond controversy; for Histology, the fact that 
 the body consists wholly of cells and cell derivatives; for Embryology, the 
 fact that all of these cells and cell derivatives develop from a single original 
 cell^the fertilized ovum. 
 
 The adult body being thus composed of an enormous number of cells, vary- 
 ing in structure and in function, forming the different tissues and organs, and 
 these cells having all developed from the single fertilized germ cell, it is the 
 province of Embryology to trace this development from the union of male 
 and female germ cells to the cessation of developmental life. 
 
 While Embryology thus properly begins with the fertilized ovum, that is, 
 with the first cell of the new individual, certain preliminary considerations are 
 essential to the proper understanding of this cell and its future development. 
 These are the structure of the ovum and of the spermatozoon and their de- 
 velopment preparatory to union. Also, as it is with cells and cell activities 
 that Embryology has largely to deal, it is necessary to consider the structure 
 of the typical animal cell and the processes by which cells undergo division or 
 proliferation. 
 
 While the subject of this work is distinctly human Embryology, it is neither 
 possible nor advisable to confine our study wholly to human material. It is not 
 possible, for the reason that material for the study of the earliest stages in the 
 human embryo (first 12 days) is entirely wanting, while human embryos of 
 under 20 days are extremely rare. Again, even later stages in human develop- 
 ment are often best understood by comparison with similar stages in lower 
 forms. For practical study by the student, human material for all even of 
 the later stages is rarely available, so that recourse must frequently be had to 
 material from lower animals. Such study is, however, usually thoroughly 
 satisfactory if the student has sufficient knowledge of comparative anatomy, and 
 the deductions regarding human development, from the study of development 
 in lower forms, are rarely in error ~ 
 
PART I. 
 
 GENERAL DEVELOPMENT. 
 
A TEXT-BOOK OF EMBRYOLOGY 
 
 CHAPTER I. 
 
 THE CELL AND CELL PROLIFERATION. 
 THE CELL. 
 
 The Typical Animal Cell (Fig. i) is a small definitely restricted mass of 
 protoplasm. It contains or has at some period of its development contained 
 two specially differentiated bodies, the nucleus and the centrosome. It may be 
 limited by a more or less definite cell membrane. 
 
 Of the ultimate structure of living protoplasm our knowledge is extremely 
 small. It is of an albuminous nature, coagulated by heat and by many chemical 
 reagents. It varies both in structure and in chemical composition in different 
 cells and is probably best considered, not as a definite structure either chemically 
 or morphologically, but as the material basis of life activities. Protoplasm can 
 usually be resolved into a formed part, spongioplasm, which takes the form of a 
 reticulum, a feltwork, or fibrillae, and an unformed homogeneous element, 
 hyaloplasm, which fills in the meshes of the reticulum or forms the perifibrillar 
 substance. Various protoplasmic inclusions are frequently found in cells. To 
 these the term metaplasm (paraplasm, deutoplasm) has been applied. Among 
 them may be mentioned plastids, fat droplets, pigment granules and various 
 excretory and secretory substances. 
 
 The NUCLEUS is usually separated from the rest of the protoplasm by a 
 nuclear membrane. Within the nucleus the nuclear membrane is continuous 
 with a nuclear reticulum which consists of two parts: a chromatic part chroma- 
 tin, and an achromatic part linin. At nodal points of the network there are 
 frequently considerable accumulations of chromatin to- form net knots (false 
 nucleoli or karyosomes). Filling the meshes of the nuclear reticulum is a fluid 
 or semifluid substance, the nucleoplasm or karyoplasm. The structure of the 
 nucleus is thus seen to correspond closely to the structure of the surrounding 
 protoplasm. This is especially evident in those cells in which there is no 
 limiting nuclear membrane, the nuclear reticulum and the cytoreticulum being 
 ccntinuous, the nucleoplasm and cytoplasm mingling. This condition, true 
 
TEXT-BOOK OF EMBRYOLOGY. 
 
 only for some resting cells, is always present in cells which are undergoing 
 mitotic division. 
 
 In addition to the net knots are the truenucleoli or plasmosomes. These are 
 spheroidal bodies which lie free in the meshes of the nuclear reticulum. They 
 vary in number in different cells and sometimes in the same cell in different 
 conditions of activity. They stain intensely with basic dyes. The function 
 of the nucleolus is not known. It has been regarded by some as material in 
 process of constructive metabolism, by others as a waste product. 
 
 The nucleus is typically spherical. Its shape may or may not be modified 
 by the shape of the cell body. Nuclei may assume very irregular shapes, as in 
 polymorphonuclear leucocytes, or they may be lobulated, as in some of the 
 
 Cell membrane " 
 
 Metaplasm 1 
 granules J 
 
 Karyosome or ) 
 net knot j 
 
 Hyaloplasm 
 Spongioplasm 
 
 Linin network 
 Nucleoplasm 
 
 Aster (attraction-sphere) 
 Centriole 
 
 ","' Plastids (metaplasm) 
 
 Chromatin network 
 Nuclear membrane 
 
 Nucleolus 
 
 Vacuole 
 
 FIG. i. Diagram of a typical cell. Bailey. 
 
 large cells of bone marrow; or a cell may have a number of nuclei. The shape 
 of the nucleus may vary considerably within comparatively short periods of time. 
 Such nuclei have been described as having amceboid movement. The size 
 of the nucleus also appears to be independent of the size of the cell body, some 
 large cells having small nuclei, while some small cells are almost completely 
 filled by their nuclei. The nucleus tends to lie near the center of the cell, yet 
 may be eccentric to any degree and appears to be suspended in the cytoplasm 
 in such a way that its location within the cell may change. In some of the lowest 
 forms no true nuclear structure exists, scattered granules of chromatin consti- 
 tuting the rudimentary nucleus, generally called a diffuse nucleus. 
 
 As the nucleus is an essential element in all reproduction, it follows that all 
 cells have been nucleated at some time in their developmental history, and that 
 the adult nonnucleated condition of some cells (e.g., respiratory epithelium) 
 is indicative of their having passed beyond the age of reproductive power. If 
 the nucleus be removed from a living cell, the cytoplasm does not necessarily 
 
THE CELL AND CELL PROLIFERATION. 3 
 
 die, but may live for some time and show active motile powers. Such a de- 
 nucleated cell has, however, lost two of its most important functions: (i) its 
 power of constructive metabolism; that is, of taking up nutritive material from 
 without and building this up into its own peculiar structure the power of 
 repair; and (2) the power of reproduction. For these reasons the nucleus has 
 been considered as especially presiding over these two cell functions. 
 
 The CEXTROSOME is a structure found in the cytoplasm near the nucleus, 
 less commonly within the nucleus. It consists typically of a minute central 
 granule, the centriole, a relatively clear surrounding area, the centrosphere, and, 
 radiating from this, the delicate rays which constitute the aster or attraction 
 sphere (Fig. i). On account of the behavior of the centrosome in relation to 
 cell division, it is usually looked upon as the dynamic center of the cell. 
 
 In the simplest forms of animal life a single cell, such as has been described 
 above, constitutes the entire individual, and as such is capable of performing 
 the functions which are recognized as characteristic of living organisms metab- 
 olism, irritability, motion, reproduction and special functions. The develop- 
 mental history of such an individual is extremely simple. The nucleus under- 
 goes division and this is accompanied or followed by division of the cytoplasm. 
 The single cell thus becomes two cells, similar in all respects to the parent cell. 
 
 In all higher, that is multicellular animals, however, the different functions 
 are distributed specifically to different cells and these cells are specifically 
 differentiated morphologically for the performance of these different functions. 
 There is, therefore, not the simple division of a parent cell to form two similar 
 daughter cells, each constituting an individual, but a differentiation from the 
 single original germ cell, the fertilized ovum, of many different kinds of cells, 
 and their specialization to form the various tissues and organs which constitute 
 the adult body. 
 
 CELL DIVISION. 
 
 In the development of the embryo, cell division of course succeeds fertiliza- 
 tion. A proper understanding, however, of the changes which take place in 
 the ovum and in the spermatozoon previous to fertilization requires the con- 
 sideration of cell division at this point. 
 
 Two types of cell division are recognized : (i) direct cell division or amitosis 
 and (2) indirect cell division or mitosis. 
 
 (i) Amitosis (Fig. 2). In this form of cell division there is no formation of 
 spin die or of chromosomes (see Mitosis, p. 4), the nucleus retaining itsreticular 
 structure during division. There is first a constriction of the nucleus, followed 
 by complete division into two daughter nuclei. During the division of the 
 nucleus a constriction appears in the cytoplasm. This increases until the 
 cytoplasm is divided into two separate masses (daughter cells), each containing 
 
TEXT-BOOK OF EMBRYOLOGY. 
 
 a nucleus. This form of cell division, which was considered by Remak and his 
 associates (1855-1858) as the only method by which cells proliferated, is now 
 known to be of rare occurrence. Flemming goes so far as to state that in the 
 higher animals amitosis never occurs as a normal physiological process in ac- 
 tively dividing cells, but is rather to be considered as a degeneration phenomenon 
 occurring in cells whose reproductive powers are on the wane. It frequently 
 results in nuclear division only, the cytoplasm remaining undivided, thus giving 
 rise to multinuclear cells. It is a common method of cell division in the 
 Protozoa. 
 
 (2) Mitosis. In this form of cell division the cell passes through a series 
 of complicated changes. These changes occur as a continuous process, but 
 
 for clearness of description it is convenient 
 to arbitrarily subdivide the process into a 
 number of phases. These are known as the 
 prophase, the metaphase, the anaphase, and 
 the telophase. Of these the prophase in- 
 cludes the changes preparatory to division 
 of the nucleus; the metaphase, the actual 
 separation of the nuclear elements; the 
 anaphase, their arrangement to form the two 
 daughter nuclei; the telophase, the division 
 of the cytoplasm to form two daughter cells 
 and the reconstruction of the two daughter 
 nuclei. 
 
 PROPHASE (Fig. 3). In actively divid- 
 
 FIG. 2. Epithelial cells from ovary of ing cells the centrosome, or, more specific- 
 cockroach, showing nuclei dividing ami- n ,, _, . , 
 
 toticaiiy. Wheeler. ally, the centnole, may be double (Fig. 3, 
 
 A), having undergone division as early, fre- 
 quently, as the anaphase of the preceding division (p. 6). Each centnole 
 is surrounded by a clear area, the centrosphere, from which radiate the 
 delicate astral rays, the whole being known as the attraction sphere (Fig. 3, 
 B, C, D). Connecting the two centrosomes are other delicate fibrils forming a 
 structure known as the central or achromatic spindle (Fig. 3, B, better developed 
 in C and D). The two centrioles with their surrounding centrospheres, astral 
 rays and connecting spindle, constitute the amphiaster. If the resting cell 
 contains only one centriole, division of the centnole with formation of the 
 amphiaster is usually the first phenomenon of mitosis, the connecting central 
 spindle fibers appearing as the centrioles move apart. 
 
 During or following the formation of the. amphiaster, important changes 
 occur in the nucleus. It increases somewhat in size and the reticulum charac- 
 teristic of the resting nucleus becomes converted into a single long thread 
 
THE CELL AND CELL PROLIFERATION. 5 
 
 (spireme thread) arranged in a closed skein closed spireme (Fig. 3, B). This 
 soon becomes more loosely arranged, the thread at the same time becoming 
 shorter and thicker and frequently broken, forming the open spireme. During 
 the formation of the spireme Jhe nucleolus and nuclear membrane usually 
 disappear, the nucleoplasm thus becoming continuous with the cytoplasm. 
 The spireme now lies with the amphiaster in the general cell protoplasm. 
 The morphological change from reticulum to spireme is apparently accom- 
 
 FIG. 3. Diagrams of successive stages of mitosis. Wilson. 
 
 A, Resting cell with reticular nucleus and true nucleus; c, two centrioles the single preceding 
 
 one having divided in anticipation of the division of nucleus and cell body. 
 
 B, Early prophase. Chromatin forming a continuous thread closed spireme; nucleolus still 
 
 present; a, centrioles surrounded by astral rays and connected by achromatic spindle. 
 
 C, Later prophase. Spireme has segmented to form chromosomes; astral rays and achromatic 
 
 spindle larger and more distinct; nuclear membrane less distinct. 
 
 D, End of prophase; ep, chromosomes arranged in equatorial plane of spindle. Wl^/ 
 
 panied by changes of a chemical nature, as the spireme thread stains much 
 more intensely than do the strands of the reticulum. 
 
 The next step is the transverse division of the spireme thread into a number 
 of segments (Fig. 3, C). These are usually at first rod-shaped, and are 
 known as chromosomes. They may remain rod-shaped or the rods may 
 become bent to form U's or Vs. Some chromosomes are spheroidal. The 
 most remarkable feature of the breaking up of the spireme thread to form 
 
6 TEXT-BOOK OF EMBRYOLOGY. 
 
 chromosomes is that the number of segments into which the thread divides, 
 while differing for different species of plants and animals, is fixed and definite 
 for each particular species. For example, in Ascaris megalocephala a very 
 convenient type for study on account of its simplicity the number of chro- 
 mosomes is 4, in the mouse 20. In man the number is not known with cer- 
 tainty, the most authoritative estimate being 24. 
 
 There are thus at this stage present in the cytoplasm, two distinct though 
 closely related structures the amphiaster and the chromosomes. These 
 together constitute the mitotic figure. As the chromosomes form they become 
 arranged in the equator of the central spindle, along what is known as the 
 equatorial plane (Fig. 3, D). When, as is frequently the case, the chromosomes 
 are U-shaped, the closed ends of the loops lie toward the center, the open ends 
 radiating. Three sets of fibers can now be distinguished in connection with the 
 centrosomes (Fig. 3, C, D) : (i) the fibers of the central spindle connecting 
 the two centrosomes; (2) the polar rays which radiate from the centriole 
 toward the periphery of the cell; (3) the mantle fibers which pass from the 
 centrosomes to the chromosomes. 
 
 The mitotic figure is at this stage known as the monaster, and its complete 
 formation marks the end of the prophase. 
 
 METAPHASE. The essential feature of the metaphase is the longitudinal 
 splitting of each chromosome into exactly similar halves (Fig. 4, E), each half 
 containing an equal amount of the chromatin of the parent chromosome. In 
 the case of U- or V-shaped chromosomes, the splitting begins at the crown 
 and extends to the open ends. The latter often remain united for a time, 
 giving the appearance of rings or loops. The significance of this equal longi- 
 tudinal splitting of the chromosomes is apparent when one considers that 
 through this means an exactly equal part of each chromosome and thus exactly 
 equivalent parts of the chromatin of the parent nucleus are distributed to the 
 nucleus of each daughter cell. 
 
 ANAPHASE. Actual division of the chromosomes having taken place, the 
 next step is their separation to form the daughter nuclei. In separating, the 
 daughter chromosomes pass along the fibers of the central spindle (Fig. 4, F), 
 apparently under the guidance of the mantle fibers, each group toward its 
 respective centrosome, around which the chromosomes finally become arranged 
 (Fig. 4, G), thus forming two daughter stars. The mitotic figure is now 
 known as the diaster. In actively dividing cells it is common for the centriole 
 to undergo division at this stage, thus making four centrioles in the cell. 
 (Fig. 4, F, G.) 
 
 TELOPHASE (Fig. 4, H). This is marked by division of the cytoplasm, 
 usually in the equatorial plane of the achromatic spindle, and the reconstruction 
 of the two daughter nuclei. Each new cell now contains a nucleus, a centrosome 
 
THE CELL AND CELL PROLIFERATION. 
 
 with its aster (or two centrioles with asters) and one-half the achromatic 
 spindle. The resting nucleus is formed by a reverse of the series of changes 
 described as occurring in the prophase, the chromosomes uniting end to end to 
 form a skein or spireme, lateral buds appearing which anastomose, thus giving 
 rise to the reticulum of the resting nucleus. The nucleolus reappears as 
 mysteriously as it disappeared during the prophase and the nuclear membrane 
 is reformed. 
 
 FIG. 4. Diagrams of successive stages of mitosis. Wilson. 
 
 E, Metaphase. Longitudinal splitting of chromosomes to form daughter chromosomes, ep; 
 
 n, cast-off nucleolus. 
 
 F, Anaphase. Daughter chromosomes passing along fibers of achromatic spindle toward centro- 
 
 somes; centrioles again divided; if, interzonal fibers of central spindle. 
 
 G, Late anaphase. Chromosomes at ends of spindle; spindle fibers less distinct; thickenings of 
 
 fibers in equatorial plane indicate beginning of cytoplasmic plate; cell body beginning to 
 divide; nucleolus has disappeared. 
 
 H, Telophase. Cell body divided; chromatic substance in each daughter nucleus as in resting 
 stage; nuclear membrane and nucleolus has reappeared in each daughter cell. 
 
 It is to be noted that the number of chromosomes which enter into the forma- 
 tion of the chromatic reticulum of the resting nucleus is the same as the number 
 of chromosomes derived from that nuclear reticulum when the cell prepares for 
 mitotic division. It is thus probable that the chromosomes maintain their in- 
 dividuality even during the resting stage. 
 
 In plant mitosis the central spindle fibers show minute chromatic thicken- 
 
8 TEXT-BOOK OF EMBRYOLOGY. 
 
 ings along the plane of future division of the cell, forming what is known as the 
 mid-body or cell-plate. This splits into two layers, between which the division 
 of the cell takes place. The formation of a distinct cell-plate in animal 
 mitosis is rare. In place of this there is a modification of the cytoplasm along 
 the line of future division, sometimes called the cytoplasmic plate. 
 
 As to what may be called the dynamics of mitosis, there has been much 
 controversy, but comparatively little has been definitely settled. 
 
 It would appear that in most cases the centrosome is the active agent in 
 initiating, and possibly in further controlling the mitotic process. Boveri, 
 for this reason, refers to the centrosome as the "dynamic center" of the cell. 
 The centriole first divides into two, around each of which an astral system of 
 fibers is formed. The origin of these fibers appears to differ in different cells. 
 Thus, in some cases Infusoria, for example the centrosome lies within the 
 nucleus and the entire mitotic figure apparently develops from nuclear struc- 
 tures. In some of the higher plants both central spindle fibers and asters 
 are formed from the spongioplasm. In still other cases for example, the eggs 
 of Echinoderms part of the figure (the asters) is developed from the cytoplasm, 
 while the fibers of the central spindle are of nuclear origin. 
 
 It must, however, be admitted that centrosome activity is not absolutely 
 essential to cell division, for there are cases in which division of the chromo- 
 somes occurs without division of the centrosome, while in the higher plants 
 mitosis occurs, although no centrosome can be distinguished at any stage of 
 the process. 
 
 The behavior of the centrosome before, during and after mitosis varies in 
 different cells. In some cells the centriole is apparently an integral part of 
 the cell, persisting throughout the resting stage. With it may remain more 
 or less of the aster, the whole constituting the already mentioned attraction 
 sphere. In other cells for example, mature egg cells the centriole with 
 its fibrils apparently entirely disappears during the resting stage. 
 
 In regard to the origin of the chromatic portion of the mitotic figure, no 
 difference of opinion exists, so evidently does it arise, as already noted, from the 
 chromatic portion of the nuclear reticulum. Its destination in the nuclear 
 reticulum of the daughter cells is equally well established. The details of the 
 formation of the chromosomes vary. Thus in some cases there is no single 
 spireme thread, the spireme being segmented from its formation, each segment 
 of course corresponding with a future chromosome. In other cases no spireme 
 whatever is formed, the chromosomes taking origin directly from the nuclear 
 reticulum. In still other cases the spireme while yet a single thread splits 
 longitudinally so that there are two threads present, the transverse divisions 
 into chromosomes taking place subsequently. 
 
 As to the time required for the mitotic process, considerable variation exists 
 
THE CELL AXD CELL PROLIFERATION. 9 
 
 The process usually requires from one- half to three-quarters of an hour, but 
 may extend over from two to three hours. 
 
 Mitosis is naturally most active wherever active growth of tissue is taking 
 place for example, in embryonic tissues, in granulation tissue, in the healing 
 of wounds, in rapidly growing tumors (usually an evidence of malignancy). 
 The earlier generations of cells derived from the fertilized ovum are indifferent 
 cells in the sense that they are capable of development into any type of tissue 
 cells. As differentiation takes place, the cells assume more definite and fixed 
 types. With differentiation, mitosis becomes less and less active and cells 
 become incapable of producing cells of any type other than their own. Finally, 
 the most highly differentiated (specialized) cells for example, muscle cells and 
 nerve cells lose entirely their powers of reproduction, and if destroyed are not 
 replaced by new cells of the same type. 
 
 What is known as multipolar or pluripolar mitosis occurs in some of the 
 higher plants, less commonly in the rapidly growing connective tissue of healing 
 wounds and in cancer cells. Such atypical mitosis has also been artificially 
 induced in rapidly dividing cells by the injection of chemical substances into the 
 tissues. In multipolar mitosis the centrosome divides into more than two 
 daughter centrosomes and not infrequently results in an unequal distribution, of 
 chromatin to the daughter cells. 
 
 References for Further Study. 
 
 BUCHXER, P.: Praktikum der Zellenlehre. Erster Teil, Berlin, 1915. 
 
 CONKLIX, E. G.: Karyo kinesis and Cytokinesis. Jour. Acad. Nat. Sci. of Philadel- 
 phia, Vol. XII, 1902. 
 
 HEIDEXHAIX, M.: Plasma und Zelle, Abteilung I, 1907, Abteilung II, 1911. 
 
 HERTWIG, O.: Die Zelle und die Gewebe. 1908. 
 
 KELLICOTT, \V. E.: General Embryology, 1913. 
 
 LILLIE, F. R.: A Contribution towards an Experimental Analysis of the Karyo kinetic 
 Figure. Science, Xew Series, Vol. XXVII, 1908. 
 
 WILSON, E. B.: The Cell in Development and Inheritance. 26. Ed., 1900. 
 
CHAPTER II. 
 THE GERM CELLS OVUM AND SPERMATOZOON 
 
 It is customary, from the biologist's point of view, to divide the cells of 
 multicellular animals, or metazoa, into two classes: (i) the somatic cells and 
 (2) the germ cells. The somatic cells constitute the various tissues and organs 
 of the body and take part in the general physiological processes during the life 
 of the individual but perish without descendants when the individual dies. 
 The germ cells, on the other hand, are confined to the gonads, or genital glands, 
 play no role in the general economy of the individual; but are so specialized 
 that under proper conditions they give rise to a new individual and thus per- 
 petuate the species. 
 
 In the entire vertebrate series of animals, and indeed in almost the whole 
 invertebrate series, the development of a new individual can take place only 
 after the union of two germ cells produced by two sexually different and mature 
 individuals. These cells are the egg (ovum, ovium) and the sperm (sperma- 
 tozoon, spermium), the former produced by the female, the latter by the male. 
 They are found in each sex in special glands the ovum in the ovary and the 
 spermatozoon in the testis from which they are detached at definite times 
 during sexual maturity. Prior to their union to form the starting point of a 
 new individual they pass through important preparatory stages which must 
 be considered along with their general characteristics. 
 
 THE OVUM. 
 
 With the exception of some neurones, the human ovum (Fig. 5) is the 
 largest cell in the body. It is spherical in shape, measuring from 0.15 mm. to 
 0.2 mm. in diameter, contains a large spherical nucleus and is surrounded by a 
 relatively thick, transparent membrane. As seen in section in the ovary it has 
 
 10 
 
THE SEXUAL ELEMENTS OVUM AND SPERMATOZOON. 
 
 11 
 
 essentially the structure of a typical cell. Around the ovum and separated 
 from it by a narrow cleft the perivitelline space is the zona pellucida, a rather 
 thick, highly refractive membrane which shows radial striations. These 
 striations are probably due to the presence of minute canals which penetrate the 
 zona. It has been suggested that these canals serve for the passage of nutri- 
 ment to the ovum. Immediately outside of the zona pellucida the epithelial 
 cells of the Graafian follicle are arranged radially in one or two layers. These 
 
 Zona 
 pellucida 
 
 FIG. 5. From a section of the ovary of a 1 2-year old girl. The primary oocyte lies in a large 
 mature Graafian follicle and is surrounded by the cells of the "germ hill" (the inner edge of which 
 is shown in the upper left-hand corner of the figure). Photograph. 
 
 constitute the corona radiata (Fig. 5). Some investigators have described a 
 thin, delicate mtelline membrane between the perivitelline space and the ovum. 
 Others have failed to observe this. 
 
 The egg protoplasm, originally called the vitellus, differs from the pro- 
 toplasm of most cells hi that it appears somewhat more opaque and coarsely 
 granular. This appearance is due to the fact that the ovum stores up within 
 itself food stuffs. These consist of fatty and albuminous substances which are 
 
12 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 later utilized in the growth and increase of the embryonic cells. The food 
 granules deutoplasm are suspended in the cytoplasm. The distribution, 
 however, of these granules in the human ovum is not uniform; a mass of them 
 being found in the center of the cell surrounding the nucleus, while an almost 
 clear zone of cytoplasm forms the periphery of the cell. 
 
 The nucleus of the ovum occupies a position near the center within the 
 deutoplasm mass, though in the ovum of a mature Graafian follicle it is almost 
 invariably slightly eccentric. It is large proportionately as the ovum is large. 
 Its structure does not differ essentially from that of any other nucleus. There 
 is a distinct nuclear membrane enclosing the usual nuclear structures the 
 nuclear liquid, the network of chromatin, the achromatic network and a single 
 
 nudeolus or germinal spot (p. 2, Fig. i). In 
 /-^ a fresh human ovum amoeboid movements 
 
 have been observed in the nucleolus. The 
 
 \ 
 
 \ significance of the nucleolus is as little known 
 ^jjSiJfc^ 5| as m anv other cell. 
 
 K A centrosome, though it may be present, 
 
 has not been observed in the human ovum. 
 
 A classification of ova has been made 
 on the basis of the amount and distribution 
 of the yolk; conditions which strongly affect 
 the subsequent processes of development. 
 The term meiolecithal is used to designate 
 ova in which the yolk granules are relatively 
 few (ova of Amphioxus, most Mammals in- 
 cluding man). Mesolecithal ova are those 
 which contain a moderate amount of yolk 
 (Amphibia.) Ova which contain a relatively 
 large amount of yolk are classed as foly- 
 
 lecithal (Reptiles and Birds). In meiolecithal eggs the yolk granules are as a 
 rule evenly distributed through the cytoplasm. In mesolecithal and polyleci- 
 thal eggs, on the other hand, the yolk is unevenly distributed, giving rise to a 
 condition known as polar differentiation ; the protoplasm is in excess at one pole 
 of the egg and the deutoplasm in excess at the opposite pole. Such ova are 
 spoken of as telolecithal. The frog's egg is a familiar example of this differ- 
 entiation, the dark side of the egg indicating an excess of cytoplasm. Inasmuch 
 as deutoplasm is generally heavier than cytoplasm, an egg with polar differ- 
 entiation, if left free to revolve, as in water, will assume a definite position 
 with the protoplasmic or animal pole above and the deutoplasmic or vegeta- 
 tive pole below. An exception to this is found, however, in the pelagic teleost 
 eggs, which float with the deutoplasmic pole upward. 
 
 FIG. 6. Semidiagrammatic representa- 
 tion of ovum of frog (Rana sylvatica). 
 The dark shading represents the cyto- 
 plasmic pole, the light shading immedi- 
 ately below represents the deutoplasmic 
 pole. The light shading around the 
 ovum represents the gelatinous sub- 
 stance (secondary egg membrane). 
 
THE SEXUAL ELEMENTS OVUM AND SPERMATOZOON. 13 
 
 In the hen's egg the cytoplasm and deutoplasm are distinct and separate 
 with no mingling of the two substances (Fig. 7). While still in-the ovary, the 
 egg consists of the yellow yolk in the form of an enormously large cell sur- 
 rounded by the zona pellucida, upon which lies a small white spot, the so- 
 called germinal disk. The disk is 3 or 4 mm. in diameter and consists of 
 finely granular protoplasm with a somewhat flattened nucleus. This disk 
 
 Germinal disk (cytoplasm) White yolk 
 
 Albumen ("white" -^^L K^T~ Shdl 
 
 Shell membrane 
 (outer layer) 
 
 Vitelline 
 
 mm mm* mmmmm \ \\ 
 
 Chalaza 
 
 . -' " 
 
 White yolk ^S^ VB&tMfSj! \f\ II 
 
 Yellow yolk (deutoplasm) 
 FIG. 7. Diagram of a vertical section through an unfertilized hen's egg. Bonnet. 
 
 alone gives rise to the embryo proper. All the rest of the mass consisting of a 
 vast number of spherules united by a small amount of cement substance, is 
 simply nutritive material or deutoplasm which is later utilized for the nourish- 
 ment of the embryo. The various structures surrounding the yolk albumen, 
 shell membrane and shell are not strictly speaking parts of the ovum, but are 
 secondary egg membranes secreted by different portions of the oviduct. 
 
 THE SPERMATOZOON. 
 
 In marked contrast to the ovum, the spermatozoon is one of the smallest cells 
 of the body, being only about fifty microns in length. The spermatozoon, as 
 seen in the seminal fluid, in any of the sexual passages, or even hi the lumen of a 
 seminiferous tubule, is a true sexual element, since it has passed through certain 
 processes which prepare it for union with the mature ovum. (See Spermatogen- 
 esis, Chap. III.) Like the ovum the spermatozoon is an animal cell of which, 
 however, both cell body and nucleus have undergone important modifications. 
 The flagellate spermatozoon, of which the human spermatozoon is an example 
 (Fig. 8), resembles a tadpole in shape and like the latter swims about by 
 means of the undulatory movements of its long slender flagellum or tail. It 
 consists of (i) a head, (2) a middle-piece or body and (3) a tail. 
 
 i. THE HEAD. This in the human spermatozoon is from three to five 
 microns long and about half as broad. On side view it appears oval; when 
 
14 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 Acrosome 
 
 Head 
 
 Body 
 
 End ring 
 
 Anterior end knob 
 Posterior end knob 
 
 Spiral fibers 
 
 .Sheath of 
 axial thread 
 
 seen on edge, it is pear-shaped, the small end being directed forward. It 
 consists mainly of nuclear material derived from the nucleus of the parent cell. 
 (See Spermatogenesis.) A thin layer of cytoplasm, the galea capitis or head- 
 
 cap, envelops the nuclear material, while in 
 front there is a sharp edge known as the 
 apical body or acrosome. In contrast to the 
 nuclear portion of the head, which of course 
 takes a basic stain, the acrosome stains with 
 acid dyes. In some forms the acrosome is 
 much larger than in man and extends 
 forward from the head-cap as a long spear, 
 sometimes barbed the perjoratorium. This 
 process perhaps assists the spermatozoon in 
 clinging to or in burrowing its way into the 
 ovum. Many peculiar types of perfora- 
 toria, for example, lance-shaped, awl- 
 shaped, spoon-shaped, corkscrew-shaped, 
 have been described and have given charac- 
 teristic names to the spermatozoa possessing 
 them. 
 
 2. THE BODY in the human sperma- 
 tozoon is cylindrical and about the same 
 length as the head. It consists of a deli- 
 cately fibrillated cord, the axial thread, sur- 
 rounded by a protoplasmic capsule. In 
 some forms (Mammals) a short clear por- 
 tion, the neck, unites the head and body. 
 In the neck there can sometimes be demon- 
 strated an anterior end knob and one or 
 more posterior end knobs to which is attached 
 the axial -filament. In man and in some 
 other forms, delicate fibers spiral fibers 
 wind spirally around that portion of the 
 axial filament which lies within the body. 
 At the posterior end of the body, the axial 
 filament passes through the end disk or end 
 ring. 
 
 3. THE TAIL in the human spermatozoon is forty to fifty microns in length; 
 is the direct continuation of the axial thread of the body; and consists of a main 
 segment thirty-five to forty-five microns in length, and a short terminal 
 segment. As in the body, the axial filament is delicately fibrillated. Sur- 
 
 Main segment 
 of tail 
 
 Axial thread 
 Capsule 
 
 Terminal 
 filament 
 
 FIG. 8. Diagram of a human sperma- 
 tozoon. Meves, Bonnet. 
 
THE SEXUAL ELEMENTS OVUM AND SPERMATOZOON. 15 
 
 rounding the axial filament is a thin cytoplasmic membrane or capsule 
 continuous with that of the body. In the human spermatozoon it is ap- 
 parently structureless; in other forms it assumes curious shapes as, for example, 
 the so-called membrana undulatoria, or wavy membrane of Amphibia, or the fine 
 membrane of some Insects.^ The terminal segment consists of the axial fila- 
 ment uncovered by any sheath. 
 
 The significance of the various parts of the spermatozoon can be best 
 understood by reference to spermatogenesis (p. 17). 
 
 Comparing the spermatozoon with a cell, the head contains the nucleus 
 while the body contains the centrosome. It is these parts of the spermatozoon 
 which are essential to fertilization. The acrosome and the tail may therefore 
 be considered as accessory structures which serve to bring and attach the 
 spermatozoon to the ovum. 
 
 Within the tubule of the testis the spermatozoa show no evidence of motile 
 power. In the semen, however, which consists mainly of fluid secretions of 
 the accessory sexual glands, they move about freely, as also in the fluids of the 
 female genital tract. Their speed has been estimated at from 1.5 to 3.5 mm. 
 per minute and enables them to swim up through the uterus and oviduct, in 
 spite of the fact that the action of the cilia lining these tracts is against them. 
 
 The life of the spermatozoon within the female genital tract is not known. 
 Moving spermatozoa have been found there seven to eight days after coitus. 
 In one case reported of removal of the tubes, living spermatozoa were found 
 three and one-half weeks after coitus. 
 
 References for Further Study. 
 
 COXKLIX, E. G.: Organ -forming Substances in the Eggs of Ascidians. Biol. Bull., 
 Vol. VIII, 1905. 
 
 KEIBEL,-F. and MALL, F. P.: Manual of Human Embryology, 1910. Vol. I, Chap. I. 
 WALDEYER, W. : In Hertwig's Handbuch der vergleichenden u. experimentellen Entwick- 
 elungslehre der Wirbeltiere. Bd. I, Teil I, 1903. Also contains extensive bibliography. 
 WILSON, E. B.: The Cell in Development and Inheritance. 2d Ed., 1900. 
 
; CHAPTER III. 
 MATURATION. 
 
 It was stated in the preceding chapter that the essential condition for the 
 production of a new individual, in practically all the animal kingdom and with- 
 out exception among the Vertebrates, was the union of two sexually different 
 cells. Since the number of chromosomes is constant for all the cells of a 
 species, such a union would cause a doubling of chromosomes unless the latter 
 were reduced to one-half their normal number. Such reduction actually takes 
 place, and forms the essential part of the maturation processes of the germ cells. 
 
 SPERMATOGENESIS MATURATION OF THE SPERM. 
 
 The spermatozoa arise from the germinal epithelium of the testis. In the 
 mammal (Fig. 9) this epithelium consists of two kinds of cells: (i) the support- 
 ing cells (of Sertoli) and (2) the spermatogenic cells in various stages of develop- 
 ment. Of the latter the basal layer consists of small round or oval cells which 
 are known as spermatogonia. Internal to these are the larger spermalocytes 
 having large vesicular nuclei with densely staining chromatin. Between these 
 and the lumen of the seminiferous tubule are several layers of small round or 
 oval cells, the spermatids. The spermatids have the reduced number of chromo- 
 somes, and by direct transformation give rise to the mature spermatozoa which 
 may either lie free in the lumen of the tubule or have their heads embedded in 
 the supporting cells (Fig. 9). 
 
 The way in which the maturation or reduction divisions take place in the 
 higher animals, such as mammals, has not been definitely shown on account 
 of the extreme minuteness of the cells and the difficulty of obtaining suitable 
 material. The following account is based on data obtained from the study of 
 lower forms (amphibia, fishes, insects, Ascaris) whose maturation processes 
 have been demonstrated with great accuracy. Ascaris (Fig. 10) and some of 
 the insects (Fig. 1 7) show the later stages with remarkable clearness. There 
 is no reason to suppose that the maturation processes of the mammalian germ 
 cells differ essentially from those of lower forms. 
 
 The spermatogonia divide by ordinary mitosis, each daughter cell receiving 
 the full or diploid number of chromosomes. After several generations some of 
 the spermatogonia pass through a period of growth and are then known as 
 primary spermatocytes. During this period important changes take place in 
 
 17 
 
18 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 the nucleus. The chromatin granules become 
 concentrated into a dense mass in which very 
 little structure is made out (Fig. 10, A). After 
 the period of growth the nucleus assumes again 
 the reticular appearance. Then when the 
 spireme is formed and segmentation occurs, 
 previous to division, only the haploid or one- 
 half the normal number of chromosomes appears. 
 This seems to be due to an actual fusion of 
 chromosomes by pairs, such fusion occurring 
 during the period of growth and being known 
 as synapsis of chromosomes. In some cases 
 the double nature of the chromosomes is still 
 visible while in other cases the fusion is com- 
 plete. 
 
 The fused chromosomes now prepare for 
 division. However, instead of dividing longi- 
 tudinally into two parts, a double splitting 
 occurs and each chromosome is divided into 
 four elements. Such a quadruple chromosome 
 is termed a tetrad (Fig. 10, E, F, G). Since 
 each tetrad represents a double chromosome, 
 the number of tetrads in any species will be 
 equal to one-half its normal number of chro- 
 mosomes. The tetrads arrange themselves in 
 the equatorial plane of the spindle and cell 
 division begins (Fig. 10, G). Each tetrad is 
 separated into two dyads, and then one dyad 
 from each tetrad goes to each of the two re- 
 sulting daughter cells or secondary spermato- 
 cytes (Fig. 10, H). A new spindle is formed 
 in each of the secondary spermatocytes and 
 the cells divide again, without the return of 
 the nucleus to the resting stage. The dyads 
 go to the equatorial plane. Each dyad is 
 separated into two monads, each daughter 
 cell or spermatid receiving one monad from 
 
 1-8, Spermatogonia lying close to the 
 
 basement membrane and multiplying 
 
 by ordinary mitosis. 9-16, Spermatogonia during period of growth, resulting in primary spermato- 
 cytes. 17, 18, 19, Primary spermatoscyte dividing. 20, Secondary spermatocytes. 21, Second- 
 ary spermatocytes dividing, resulting in spermatids (22-25). 26-31, Transformation of spermatids 
 into spermatozoa, a few of which are seen fully formed (32). 
 
MATURATION. 
 
 19 
 
 each dyad (Fig. 10, 7, K, L). A primary spermatocyte gives rise therefore to 
 four spermatids in which the number of chromosomes is reduced to one-half 
 the normal (Fig. io,Z). 
 
 After the last spermatocyte division and the resulting formation of the 
 spermatid, the nucleus of the latter acquires a membrane and intranuclear net- 
 
 FIG. 10. Reduction of chromosomes in spermatogenesis in Ascaris megalocephala (bivalens). 
 Brauer, Wilson. A G, Successive stages in the division of the primary spermatocyte. The original 
 reticulum undergoes a very early division of the chromatin granules which then form a doubly split 
 spireme (5). This becomes shorter (C), and then breaks in two to form the 2 tetrads (D, in p'rofile, 
 E, on end). F, G, H, First division to form 2 secondary spermatocytes, each receiving. 2 dyads. /, 
 Secondary spermatocyte. /, K t The same dividing. Z,, Two resulting spermatids, each containing 
 2 single chromosomes. 
 
 work, thus passing into the resting condition. Without further division the 
 spermatid now becomes transformed into a spermatozoon. This is accomplished 
 by rearrangement and modification of its component structures (Fig. 1 1). The 
 ccntrosome either divides completely, forming two centrosomes, or partially, 
 forming a dumb-bell-shaped body between the nucleus and the surface of the 
 
20 TEXT-BOOK OF EMBRYOLOGY. 
 
 cell. The nucleus passes to one end of the cell and becomes oval in shape. 
 Its chromatin becomes very compact and is finally lost in the homogeneous 
 chromatin mass which forms the greater part of the head of the spermatozoon. 
 Both centrosomes apparently take part in the formation of the middle piece. 
 The one lying nearer the center becomes disk-shaped and attaches itself to the 
 posterior surface of the head. The more peripheral centrosome also becomes 
 disk-shaped and from the side directed away from the head a long delicate 
 
 Head 
 
 Anterior end knob 
 Posterior end knob 
 
 Head 
 
 , Anterior end knob 
 Posterior end knob 
 - End ring 
 
 Nucleus 
 
 Cytoplasm 
 Proximal centrosome 
 
 Distal centrosome 
 
 Tail 
 
 FIG. ii. Transformation of a spermatid into a spermatozoon (human). Schematic. 
 
 Meves, Bonnet. 
 
 thread grows out the axial filament. The central portion of the outer cen- 
 trosome next becomes detached and in Mammals forms a knob-like thickening 
 end knob at the central end of the axial filament. In Amphibians this part 
 of the outer centrosome appears to pass forward and to attach itself to the inner 
 centrosome. In both cases the rest of the outer centrosome in the shape of a 
 ring passes to the posterior limit of the cytoplasm. As the two parts of the 
 posterior centrosome separate, the cytoplasm between them becomes reduced 
 in amount, at the same time giving rise to a delicate spiral thread the spiral 
 
MATURATION. 
 
 21 
 
 filament which winds around the axial filament of the middle piece. Mean- 
 while the axial filament has been growing in length and part of it projects be- 
 yond the limits of the cell. The cytoplasm remaining attached to the anterior 
 part of the filament surrounds it as the sheath of the middle piece. In Mam- 
 mals there appears to be more cytoplasm than is needed for the formation of 
 the sheath of the middle piece, and a large part of it degenerates and is cast 
 aside. The sheath which surrounds the main part of the axial filament appears 
 in some cases at any rate to develop from the filament itself. The galea capitis 
 or delicate film of cytoplasm which covers the head is undoubtedly a remnant 
 of the cytoplasm of the spermatid. 
 
 The developing spermatozoa lie with their heads directed toward the base- 
 ment membrane, and attached, probably for purposes of nutrition, to the free 
 ends of the Sertoli cells (Fig. 9). Their tails often extend out into the lumen 
 of the tubule. When fully developed they become detached from the Sertoli 
 cells and lie free in the lumen of the tubule. 
 
 MATURATION OF THE OVUM. 
 
 The female germ cell, before it is fertilized, goes through a process of matu- 
 ration similar to that of the male germ cell. The result is essentially the same 
 
 m.pn. 
 
 FIG. 12. From sections of ova of the mouse, showing three stages in the maturation process. 
 
 A, Ovum showing prophase of maturation division. /, fat; z.p., zona pellucida. 
 
 B, Ovum showing maturation spindle with chromatin segments undivided. 
 
 C, Ovum showing diaster stage of maturation division, formation of ist polar body (p.b.), and sperm 
 
 nucleus (male pronucleus, m.pn.) just after its entrance. Sobotta. 
 
 the mature ovum contains a reduced number of chromosomes. There is this 
 difference, however, that while the chromatin elements are distributed equally 
 during the reduction divisions, one cell only retains practically all the cytoplasm 
 and deutoplasm present in the primary oocyte. This cell becomes the func- 
 tional ovum while the other cells are pinched off as minute bodies, containing 
 but little of the cytoplasm, which are known as polar bodies and eventually 
 degenerate and die (Figs. 12 and 13). 
 
 The early maturation stages of the female sex cell are very similar to those 
 
22 TEXT-BOOK OF EMBRYOLOGY. 
 
 of the male. The oogonia contain the diploid number of chromosomes and 
 divide by ordinary mitosis. After several generations they pass through a 
 period of growth and are then known as primary oocytes. During the growth 
 period there occurs a condensation of the chromatin, and synapsis of the chro- 
 mosomes probably takes place at this time. The nucleus then resumes its 
 reticular structure. Following this the spireme is formed, preparatory to divi- 
 sion, and segments into the haploid number of chromosomes. From this stage the 
 process varies somewhat in different animals. In Ascaris, whose diploid num- 
 ber of chromosomes is four, both maturation divisions occur after the sperm 
 has entered the egg and lies embedded there as the male pronucleus (Fig. 14). 
 An achromatic spindle forms near the surface of the ovum and the two tetrads 
 go to the equatorial plane (Fig. 14, E). Each tetrad separates into two dyads, 
 and one dyad from each tetrad passes into a small mass of cytoplasm which 
 becomes detached from the egg cell as the first polar body (Fig. 14, F, G, H). 
 
 FIG. 13. From sections of ova of the mouse, showing the polar bodies (p.b.) and three stages of the 
 male (m.pn.) and female (J.pn.) pronuclei. Sobotta. 
 
 A new spindle forms without the return of the nucleus to the resting stage, and 
 each dyad divides into two monads. The second polar body is now given off in 
 the same manner as the first. One monad from each dyad passes into a small 
 mass of cytoplasm and is separated from the egg cell (Fig. 14, H, I,'J, K). 
 The maturation process is now complete. The nucleus of the mature ovum 
 contains the haploid number of chromosomes and is ready for union with the 
 male pronucleus. 
 
 The maturation of the mouse ovum, recently described by Mark and Long, 
 may be taken as an example of mammalian maturation. The diploid number 
 of chromosomes is twenty, but when the growth of the primary oocyte is com- 
 pleted and the cell prepares for division only ten chromosomes are present. 
 Each chromosome is V-shaped and shows the structure of a tetrad. While 
 still in the Graafian follicle the first polar body is given off and lies as a small 
 globule beneath the zona pellucida (Fig. 13, A). The egg cell and the first 
 polar body constitute secondary oocytes, comparable with the secondary sper- 
 
MATURATION. 
 
 23 
 
 matocytes of the male. The egg now leaves the ovary and reaches the oviduct. 
 Jf the ovum is fertilized, another spindle forms and a second polar body is 
 
 FiG.i4. Maturation of the ovum of Ascaris megalocephala (bivalens). Boveri, Wilson. A, 
 The ovum with the spermatozoon just entering at x* ; the egg nucleus contains 2 tetrads (one not 
 clearly shown), the somatic number of chromosomes being 4. B, Tetrads in profile. C, Tetrads 
 on end. D, E, First spindle forming. F, Tetrads dividing. G, First polar body formed, containing 
 2 dyads; 2 dyads left in the ovum. H, 7, Dyads rotating in preparation for next division. /, 
 Dyads dividing. K, Each dyad divided into 2 single chromosomes, thus completing the reduction, 
 
 given off. The nucleus of the mature ovum or female pronucleus, with the 
 haploid number of chromosomes, is now ready for union with the male 
 pronucleus. 
 
24 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 Comparing maturation in the male and female sex cells (Fig. 16), it is to be 
 noted that the spermatogonia and oogonia proliferate by ordinary mitosis, 
 maintaining the somatic or diploid number of chromosomes up to a certain 
 period in their life history. They then enter upon a period of growth in size, 
 resulting in primary spermatocytes and primary oocytes (Fig. 16). When 
 these prepare for division the nuclear reticulum in each case resolves itself into 
 the haploid number of chromosomes. During division this reduced number is 
 given to each resulting secondary spermatocyte or oocyte. 
 
 There is, however, this marked peculiarity about the division of the primary 
 oocyte, that while the division of the nuclear material is equal the division of the 
 cytoplasm is very unequal, most of the latter remaining in one cell, the secondary 
 
 FiG. 15. From section of ovum (primary oocyte) of the mouse, showing first maturation 
 spindle. Note the 12 chromatin segments, the somatic number of chromosomes being 24. The 
 ovum is surrounded by the zona pellucida (z.p.) and the corona radiata. Sobotta. 
 
 oocyte proper. The other cell, very small owing to its lack of cytoplasm, is 
 extruded from the oocyte proper as the first polar body (Fig. 16). The same 
 condition obtains in the next division. One cell, the mature ovum, retains 
 most of the cytoplasm, the other being detached as the second polar body (Fig. 
 16). In some cases the first polar body also divides. Thus the primary oocyte 
 gives rise to three or four cells, each of which has the reduced number of chromo- 
 somes. One of them becomes the mature ovum, the others are cast off as 
 apparently useless and eventually die. The primary spermatocyte, on the other 
 hand, gives rise to four functioning cells which are equal in cytoplasmic as well 
 as in chromatin content (Fig. 16). 
 
 The apparent difference between maturation of the male and female sex 
 
MATURATION. 
 
 25 
 
 cells the single functional cell in the female as contrasted with four in the male 
 loses some of its character when one notes that in some forms the polar bodies 
 are not so rudimentary as is generally the case. Thus in certain forms one or 
 more of the polar bodies may develop into cells very similar to the mature egg- 
 cell, may be penetrated by spermatozoa, and may even be fertilized and proceed 
 a short distance in segmentation. There is perhaps warrant for considering 
 the polar bodies ar rudimentary or abortive ova. 
 
 The time of formation of the polar bodies varies in different animals* In 
 a few (Echinoderms) they are formed before the sperm enters the egg. In 
 
 Oogonia 
 
 Primary 
 oocyte 
 
 Secondary 
 oocyte 
 
 Mature 
 ovum 
 
 A 
 
 Spermatogonia 
 
 . / 
 
 \ 
 
 A /\ 
 
 Proliferation 
 
 A A 
 
 t\ l\ 
 
 /' A A \ 
 
 Primary 
 spermatocyte 
 
 
 
 A 
 
 Growth 
 Secondary 
 spermatocyte 
 
 / 
 
 (X 
 
 .... A 
 
 Spermatid 
 
 / 
 
 \ l\ 
 
 w <\ 
 
 
 1 
 
 
 Prolifera- 
 tion 
 
 Growth 
 
 Maturation 
 
 Trans- 
 formation 
 
 FIG. 16. Diagrams representing the histogenesis of (a) the female sex cells and (6) the male sex 
 
 cells. Modified from Boveri. 
 
 Ascaris they are both formed after the entrance of the sperm. In other forms, 
 like the mouse, the first polar body is formed while the egg is still in the Graafian 
 follicle, the second one after the entrance of the sperm. 
 
 From the data in the above description it is evident that the phenomena of 
 maturation are essentially similar in the male and female sex cells. In the 
 female two or three of the cells are indeed abortive, probably in order to insure 
 a large amount of food material to the functioning ovum; but the result, the 
 reduction of the number of chromosomes in the mature sex cell to one-half the 
 number characteristic of other cells of the species, is always the same. 
 
 Significance of Mitosis and Maturation. 
 
 The earlier investigators regarded maturation merely as a means of reducing 
 the number of chromosomes in the mature germ cells, so as to prevent a dou- 
 
26 TEXT-BOOK OF EMBRYOLOGY. 
 
 bling of chromatin material at the subsequent fertilization. This, however, 
 seems to be but a minor object of maturation. As a matter of fact, the reduc- 
 tion of the chromatin mass is not one-half but three-quarters and even more. It 
 is also well known that the chromatin mass increases or diminishes under cer- 
 tain conditions during the life history of a cell. 
 
 The chief significance of maturation is to be considered rather from the 
 standpoint of heredity. Modern biologists believe that the chromatin particles 
 are the bearers of the hereditary qualities of the cell. During mitosis the chro- 
 matin granules arrange themselves in a continuous thread, the spireme, which 
 differs qualitatively in different regions. The chromosomes, which are only 
 segments of the spireme, likewise differ from end to end. In ordinary mitosis 
 these chromosomes split longitudinally, half of each chromosome going to each 
 of the resulting daughter cells. This is an equational division in which the 
 chromatin material is exactly halved. 
 
 In maturation, however, a synapsis of the chromosomes takes place, the 
 latter fusing in pairs. The chromosomes of each pair are probably separated 
 again in one of the subsequent maturation divisions, the reduction division. 
 If the chromosomes are qualitatively different, then the mature germ cells re- 
 sulting from this division will be of two different kinds, varying more or less 
 in their content of hereditary factors. Experimental evidence confirms this 
 interpretation of maturation. 
 
 There is another interesting point to be considered. The recent work of 
 cytologists leads to the assumption that the fusion of chromosomes during syn- 
 apsis is not a matter of chance, but takes place in a very definite manner. The 
 chromosomes in the primordial germ cells seem to form a series of homologous 
 pairs the members of which fuse during synapsis. The individual pairs can 
 often be distinguished from other pairs by differences in shape or size. There 
 is much evidence to support the belief that each pair consists of one paternal 
 and one maternal chromosome, which had been brought together at the ante- 
 cedent fertilization. This seems to indicate also, as mentioned on page 7, 
 that the chromosomes retain their identity even when resolved into the chro- 
 matic reticulum of the resting nucleus. The reduction division will separate the 
 fused chromosomes, and the resulting mature germ cells will be either paternal 
 or maternal in their chromatic constitution. The maturation processes there- 
 fore produce a segregation of the paternal and maternal chromosomes. 
 
 The cytological data described above, which support and in turn are sup- 
 ported by a great mass of experimental evidence, illustrate Mendel's "law of 
 segregation." This law is that "the units contributed by the two parents 
 separate in the germ cells without having had any influence upon each other." 
 For instance, when a mouse with gray coat color is mated with a mouse with 
 black coat color, one parent contributes a unit for gray and the other a unit 
 
MATURATION. 
 
 27 
 
 for black. These units will separate during the maturation of the germ cells, 
 and the resulting spermatozoa and ova will again recover the pure paternal or 
 maternal units. 
 
 Sex Determination. 
 
 In the great bulk of cytological and experimental studies of recent years 
 there is abundant evidence for the belief that certain chromosomes play an 
 
 FIG. 17. Stages in the spermatogenesis of a grasshopper (Stenobothrus viridulus). Meek, i, 
 Spermatogonium in process of division, having 17 chromosomes (8 pairs and one odd). 2, Repre- 
 senting growth period of spermatogonium. 3-6, Division of the primary spermatocytes sixteen of 
 the chromosomes are paired while the "accessory" has no mate and passes as a whole to one of the 
 two secondary spermatocytes. 7-8, Division of the secondary spermatocyte with the odd chromo- 
 some, the latter splitting and giving one-half to each resulting spennatid. x, "Accessory" chromo- 
 
 some. 
 
 important part in the determination of sex. In the grasshopper (Stenobothrus 
 viridulus) the somatic number of chromosomes in the male is seventeen and in 
 the female eighteen. Owing to the odd number there is an unusual complica- 
 tion in the maturation of the male germ cell. When synapsis occurs eight pairs 
 
28 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 of chromosomes are formed but the odd chromosome, which can usually be 
 distinguished by its appearance, is left without a mate. At the first maturation 
 division this univalent chromosome does not divide but passes as a whole to one 
 of the two resulting cells, thus giving two kinds of secondary spermatocytes 
 (Fig. 17, 4 and 5, x). When the secondary spermatocytes divide, however, the 
 odd chromosome in one of them also divides like the other chromosomes, each 
 of the resulting spermatids receiving one-half (Fig. 17, 7 and 8, x). Thus two 
 kinds of sperms are formed in equal numbers, containing respectively eight and 
 nine chromosomes. The odd chromosome is also known as the accessory or 
 X-chromosome. 
 
 Germinal 
 
 epithelium 
 
 kPll&LUm MV-V- ."*afi 
 
 granulosum ^s&ss.^ 
 
 ^*3* 
 
 ^^P 
 
 ^^cx 
 
 -*^Po\ 
 
 - ~' ~~~. .'- ^ 
 
 Tunica albuginea 
 
 x ;->%" 
 
 V^^i-z'''. 
 s, JPp^ 
 
 Germ hill Theca folKcu ii 
 with ovum (vascular layer) 
 
 ^3 
 
 iw^ 
 
 EKIK I 
 
 WM *; 
 
 
 1 
 1 
 
 VHvfT > i 
 
 ml 
 
 Theca folliculi (fibrous layer) - 
 
 & -" 
 
 
 
 at ; 
 
 
 
 Kf. i'J'i 
 
 
 Stratum granulosum 
 
 /.^'//'^ 
 
 
 1 
 
 
 ../^>- " '. 
 
 s. 
 
 
 
 i^^ ^s%. 
 
 tjS&ii 
 
 , 
 
 FIG. 1 8. From section of human ovary, showing mature Graafian follicle ready to rupture. 
 
 Kollmann's Atlas. 
 
 In the ovum no such complication arises, there being two "accessory" 
 chromosomes which unite in synapsis. All the mature ova will therefore con- 
 tain nine chromosomes. As a result, there are two combinations possible when 
 the male and female sex cells unite : an ovum may be fertilized by a sperm con- 
 taining either eight or nine chromosomes. In the first case the somatic number 
 in the fertilized egg will be seventeen and the egg will develop into a male. In 
 the second case the somatic number will be eighteen and the resulting individual 
 will be a female. In the example given, therefore, the presence or absence 
 of the "accessory" or odd chromosome will determine the nature of the sex 
 produced. 
 
 The presence of "accessory" chromosomes has been demonstrated in many 
 Invertebrates, especially Insects. Recently they have also been described in 
 
MATURATION. 
 
 29 
 
 several vertebrates such as the rat, fowl, guinea-pig, and even man. In many 
 cases the "accessory" chromosome of the male germ cell has a mate which 
 differs, however, in some way (size, appearance, etc.) and is designated the Y- 
 chromosome. An ovum fertilized by a spermatozoon containing the Y-chro- 
 mosome will give rise to a male ; if fertilized by one containing the X-chromosome 
 the egg will develop into a female. 
 
 There are many cases, particularly among parthenogenetic forms, where 
 sex cycles arise, which cannot be explained by chromosomal behavior. In 
 these cases nutrition seems to play an important part in determining the sex of 
 the individual. But as to the great majority of forms investigated, the weight 
 of evidence supports the view that the chromosomes are the chief agents in sex 
 determination. 
 
 OVULATION AND MENSTRUATION. 
 
 By ovulation is meant the periodic discharge of the ovum from the Graafian 
 follicle and ovary. By menstruation is meant the periodic discharge of blood 
 
 FIG. 19. Showing ovary opened by longitudinal incision. The ovum has escaped through the 
 tear in the surface of the ovary. The cavity of the follicle is filled with a clot of blood (corpus hacmor- 
 rhagicum) and irregular projections composed of lutein cells. Kollmann's Atlas. 
 
 from the uterus associated with structural changes in the uterine mucosa. The 
 two phenomena are usually associated although either may occur independently 
 of the other. They normally occur every twenty-eight days. That ovulation 
 and menstruation are not necessarily dependent upon each other and that either 
 may occur without the other has been proved by a number of observations; 
 thus the occurrence of fertilization during lactation when the menstrual func- 
 tion is in abeyance; the occurrence of impregnation in young girls before the 
 
30 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 onset of the menstrual periods and in women a number of years after the meno- 
 pause. Leopold reports the examination of twenty-nine pairs of ovaries on 
 successive days after menstruation and the finding of Graafian follicles just 
 ruptured or just ready to rupture on the eighth, twelfth, fifteenth, eighteenth, 
 twentieth and thirty-fifth days. He reports also five cases in which there were 
 no evidences of ovulation during menstruation. 
 
 At the time of ovulation the mature follicle, which has a diameter of 8 to 12 
 mm., occupies the entire thickness of the ovarian cortex, its theca being in con- 
 tact with the tunica albuginea (Fig. 18). Thinning of the follicular wall nearest 
 the surface of the ovary, and increase in the amount of the liquor folliculi, thus 
 
 Point of rupture 
 
 Lutein cells 
 
 Corpus haemorrhagicum 
 
 Blood vessel of theca 
 
 Cavity of follicle 
 
 Theca folliculi 
 
 Ovarian stroma 
 
 Stratum granulosum 
 
 FIG. 20. From section of human ovary, showing early stage in formation of corpus luteum. 
 
 Kollmann's Alias. 
 
 causing increased intrafollicular pressure, are followed by the rupture of the 
 follicle through the surface of the ovary and the escape of the ovum together 
 with the liquor folliculi and some of the follicular cells. 
 
 The escaped ovum normally passes into the fimbriated end of the Fallopian 
 tube and so to the uterus. In exceptional cases it may remain in the tube after 
 fertilization and so give rise to a tubal pregnancy, or, falling into the abdominal 
 cavity and becoming there fertilized, to an abdominal pregnancy. Both are 
 known as ectopic gestations. 
 
 As the ovum escapes from the follicle there is more or less bleeding into the 
 follicle from the torn vessels of the theca. Closure of the opening in the follicle 
 results in a closed cavity containing a blood clot, the corpus hamorrhagicum, 
 
MATURATION. 
 
 31 
 
 (Fig. 19) which then becomes gradually transformed into the corpus luteum. 
 Large cells containing fat droplets and yellow pigment (lutein granules) appear 
 around the blood clot and then increase in number until they replace the clot 
 (Figs. 20 and 21). These cells, which are called lutein cells, are considered by 
 some as derivatives of the connective-tissue cells of the theca folliculi and by 
 others as derivatives of the stratum granulosum of the follicle. The latter 
 view seems the more probable. Ingrowth of strands of connective tissue fol- 
 
 Point of rupture 
 
 Connective tissue 
 
 Connective tissue 
 from theca 
 
 Theca folliculi 
 
 Remnant of corpus 
 hsemorrhagicum 
 
 Blood vessels 
 of theca 
 
 FIG. 21. From section of human ovary, showing later stage of corpus luteum than Fig. 20. 
 
 Kollmann's Atlas. 
 
 lows the development of the lutein cells and gradually this connective tissue 
 replaces the mass of lutein cells which undergo degeneration and absorption. 
 The corpus luteum thus gives way to dense connective tissue, the corpus albicans. 
 This body persists for a long period, gradually retracting to an almost micro- 
 scopic scar. 
 
 The rapidity with which the changes, both constructive and destructive, 
 take place in the corpus luteum, appears to be largely dependent upon whether 
 the egg which escaped from the follicle is or is not fertilized. If ovulation is 
 
32 TEXT-BOOK OF EMBRYOLOGY. 
 
 not followed by fertilization the corpus luteum reaches the height of its develop- 
 ment in about twelve days, and within a few weeks has almost wholly disap- 
 peared. If, on the other hand, pregnancy supervenes, the corpus luteum be- 
 comes much larger, does not reach its maximum development until the fifth or 
 sixth month and is still present at the end of pregnancy. The above differences 
 have led to the distinction of the corpus luteum of pregnancy or the true corpus 
 luteum, and the corpus luteum of menstruation, or the false corpus luteum, al- 
 though there are no actual microscopic differences between the two. 
 
 References for Further Study. 
 
 BOVERI, T.: Zellstudien. Jena, 1887-1901. 
 
 BUCHNER, P.: Praktikum der Zellenlehre, Erster Teil, Berlin, 1915. 
 
 CHILD, C. M.: Studies on the Relation between Amitosis and Mitosis. Biolog. Bull., 
 Vol. XII, Nos. 2, 3, 4; Vol. XIII, No. 3, 1907. 
 
 CONKLIN, E. G.: The Embryology of Crepidula. Jour, of Morphol., Vol. XIII, 1897. 
 
 CRAGIN, E. B.: Text-book of Obstetrics, 1915. 
 
 HERTWIG, R.: Eireife, Befruchtung u. Furchungsprozess. In Hertwig's Handbuch der 
 vergleichenden u. experimentellen Entwickelungslehre der Wirbeltiere. Bd. I, Teil I, 1903. 
 Also contains extensive bibliography. 
 
 KEIBEL, F. and MALL, F. P.: Manual of Human Embryology. Vol. I, Chap. VII, 
 Philadelphia, 1910. 
 
 KELLICOTT, W. E.: General Embryology, 1913. 
 
 LONG, J. A. and MARK, E. L.: The Maturation of the Mouse Ovum. Carnegie Insti- 
 tution, Washington, D. C., 1911. 
 
 MORGAN, T. H.: Heredity and Sex, 1913. 
 
 SOBOTTA, J.: Die Befruchtung und Furchung des EiesderMaus. Archiv f. mik. Anato- 
 mie; Bd. XLV, 1895. 
 
 SOBOTTA, J.: Ueber die Bildung des Corpus luteum beim Meerschweinchen. Anal. 
 Hefte, Bd. XXXII, Heft XCVI, 1906. 
 
 VON LENHOSSEK, M.: Untersuchungen liber Spermatogenese. Archiv f. mik. Anatomie, 
 Bd. LI, 1898. 
 
 WILLIAMS, J. W.: Text-book of Obstetrics. New York, 1903. 
 
 WILSON, E. B.: The Cell in Development and Inheritance. 2d Ed., 1900. 
 
 WILSON, E. B. : Observation on the Maturation Phenomena in Certain Hemiptera. Jour, 
 of Exper. Zool., Vol. 13, 1912. 
 
CHAPTER IV. 
 FERTILIZATION. 
 
 When the complex maturation processes described in the preceding chapter 
 are completed, the spermatozoon is ready for union with the mature ovum. 
 This union, which forms the starting point of a new individual in all sexual 
 reproduction, is known as fertilization, and the resulting cell is the fertilized 
 oi'iim. 
 
 The details of the process vary in different animals. Its essence is the 
 entrance of the spermatozoon into the ovum and the union of the nucleus of 
 the spermatozoon with the nucleus of the ovum. At the time of its entrance 
 into the egg, the sperm head is small and its chromatin extremely condensed 
 (Fig. 22, 2). Soon after entering the ovum, however, the sperm head under- 
 goes development into a typical nucleus, the male pronudeus (Figs. 22, 3, and 
 13, C). This male pronucleus is to all appearances exactly similar in structure 
 to the nucleus of the egg, which latter is now known as the female pronucleus. 
 The chromatin networks in both pronuclei next pass into the spireme stage, the 
 spiremes segmenting into chromosomes of which each pronucleus contains one- 
 half the somatic number. The nuclear membranes meanwhile disappear and 
 the chromosomes lie free in the cytoplasm. During these changes in the pro- 
 nuclei, the amphiaster has formed and the male and the female chromosomes 
 mingle in its equatorial plane (Fig. 22, 5). At this stage no actual differentia- 
 tion can be made between male chromosomes and female chromosomes, the 
 differentiation shown in Fig. 22, 5, being schematic. The picture is now that 
 of the end of the prophase of ordinary mitosis, the somatic number of chromo- 
 somes being arranged in a plane midway between the two centrosomes. With 
 the mingling of male and female chromosomes fertilization proper comes to an 
 end. The further steps are also identical with those of ordinary mitosis. Each 
 chromosome splits longitudinally into two exactly similar parts (Fig. 22, 5), 
 one of which is contributed to each daughter nucleus (Fig. 22, 6), and the cell 
 body divides into two equal parts. (For details of succeeding anaphase and 
 telophase see p. 6.) There thus result from the first division of the fertilized 
 ovum, two cells which are apparently exactly alike and each of which contains 
 exactly the same amount of male and of female chromosome elements (Fig. 22, 6). 
 
 The amphiaster of the fertilized ovum appears to develop as in ordinary 
 mitosis. As to the origin of the centrosomes, however, much uncertainty still 
 
 33 
 
34 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 exists. The middle piece of the spermatozoon always enters the ovum with the 
 head. It has already been shown (p. 24) that one or two spermatid centro- 
 somes take part in the formation of the middle piece. Male centrosome ele- 
 ments are therefore undoubtedly carried into the ovum in the middle piece. It 
 
 Zona pellucida 
 
 Nucleus 
 ^7=^" Spermatozoon 
 
 Female 
 s* pronucleus 
 
 Head of 
 
 spermatozoon 
 with centrosome 
 
 Female pronucleus 
 
 Male pronucleus 
 
 . Chromosomes of 
 female pronucleus 
 
 *^ Chromosomes of 
 male pronucleus 
 
 "Centrosome 
 
 Centrosome 
 
 Male pronucleus 
 Female pronucleus 
 
 Chromosome from 
 female pronucleus 
 
 rr"I^^ Chromosome from 
 / male pronucleus 
 
 Centrosome 
 
 FIG. 22. Diagram of fertilization of the ovum. (The somatic number of chromosomes is 4.) 
 
 Boveri, Bohm and von Davidoff. 
 
 is equally well known, for some forms at least, that the centrosome of the ovum 
 disappears just after the extrusion of the second polar body. In a considerable 
 number of forms the development of the centrosome of the fertilized egg from, 
 or in close relation to the middle piece of the spermatozoon has been observed. 
 The details of the process as it occurs in the sea-urchin have been carefully 
 
FERTILIZATION. 
 
 35 
 
 described by Wilson. In cases of this type the tail of the spermatozoon re- 
 mains outside the egg while the head and middle piece, almost immediately 
 
 FIG. 23. Fertilization of the ovum of Thalassema. Griffin. 
 ^ , Male pronucleus, **, female pronucleus. 
 
 after entering, turn completely around so that the head points away from the 
 female pronucleus (Fig. 23, a). An aster with its centrosomes next appears, 
 developing from, or in very close relation to the middle piece. The aster and 
 
36 TEXT-BOOK OF EMBRYOLOGY. 
 
 sperm nucleus now approach the female pronucleus, the aster leading and its 
 rays rapidly extending. On or before reaching the female pronucleus the aster 
 divides into two daughter asters (Fig. 23, b) which separate with the formation 
 of the usual central spindle, while the two pronuclei unite in the equatorial 
 plane and give rise to the chromosomes of the cleavage nucleus (Fig. 23, c and 
 d). In the sea-urchin the polar bodies are extruded before the entrance of the 
 spermatozoon. In cases where the polar bodies are not extruded until after 
 the entrance of the spermatozoon (Ascaris, Fig. 14) the amphiaster forms while 
 waiting for their extrusion, the nuclei joining subsequently. When the sperm 
 head finds the polar bodies already extruded, union of the two pronuclei may 
 take place first, followed by division of the centrosome and the formation of the 
 amphiaster. 
 
 The coming together of ovum and spermatozoon is apparently determined 
 in some cases by a definite attraction on the part of the ovum toward the sperma- 
 tozoon. This attraction seems to be of a chemical nature, but is often not lim- 
 ited to the attraction of spermatozoa of the same species. Foreign spermatozoa 
 will be attracted and will enter the ovum if they are physically able to do so. 
 The entrance of these spermatozoa may even start the process of cleavage, 
 though such cleavage is usually abnormal and does not progress very far. That 
 this attraction is not dependent upon the integrity of the ovum as an organism 
 is shown by the fact that small pieces of egg cytoplasm free from nuclear ele- 
 ments exert the same attractive force, so that spermatozoa are not only attracted 
 to them, but will actually enter them. In other cases the stimulus for fertiliza- 
 tion is obviously one of contact. The spermatozoa of some Fishes will swim 
 around at random until they touch any object when they become attached and 
 are unable to escape. Fertilization in these cases is therefore a matter of chance 
 favored by the enormous number of sperms produced, and by the special breed- 
 ing habits which insure a close proximity of sperms and eggs. 
 
 Of eggs which are enclosed by a distinct membrane, the vitelline membrane, 
 some (e.g., those of Amphibians and of Mammals) are permeable to the sper- 
 matozoon at all points; others have a definite point at which the spermatozoon 
 must enter, this being of the nature of a channel through the membrane the 
 micropyle. In some instances a little cone-shaped projection from the surface 
 of the egg, the attraction cone (Fig. 22, i), either precedes or immediately fol- 
 lows the attachment of the spermatozoon to the egg. Instead of a projection 
 there may be a depression at the point of entrance. 
 
 There seems to be no question that but one spermatozoon has to do with 
 the fertilization of a particular ovum. In Mammals only one spermatozoon 
 normally pierces the vitelline membrane although several may penetrate the 
 zona pellucida (Fig. 22, i) to the peri vitelline space. Should more than one 
 spermatozoon enter such an egg as, for example, in pathological polyspermy 
 
FERTILIZATION. 
 
 37 
 
 the result is an irregular formation of asters and polyasters (Fig. 24) and the 
 early death of the egg either before or soon after a few attempts at cleavage. 
 In some Insects, and in Selachians, Reptiles and Birds, a number of sperma- 
 tozoa normally enter an ovum, but only one goes on to form a male pronucleus. 
 The ovum thus not only exerts an attractive influence toward spermatozoa, 
 but it apparently exerts this influence only until the one requisite to its fertiliza- 
 tion has entered, after which it appears able to protect itself against the further 
 entrance of male elements. As to the means by which this is accomplished 
 little is known, although several theories have been advanced. It may be that 
 when the single spermatozoon necessary to accomplish fertilization has entered 
 the ovum, it sets up within the ovum such changes as to destroy the attractive 
 
 FIG. 24. Polyspermy in sea-urchin eggs treated with 0.005 P er cen t. nicotine solution. O. and R. 
 
 Hertwig, Wilson. 
 
 B, Showing ten sperm nuclei, three of which have conjugated with female pronucleus. C, Later 
 stage showing polyasters formed by union of sperm amphiasters. 
 
 powers of the ovum toward other spermatozoa, or as even to prevent their 
 entrance. In the case of eggs where the spermatozoon enters through a micro- 
 pyle, it has been suggested that the tail of the first spermatozoon remaining in 
 the opening might effectually block the entrance to other spermatozoa; or the 
 passage of the first spermatozoon might set up such mechanical or chemical 
 changes in the canal as would prevent further access. In most cases of eggs 
 which have no vitelline membrane previous to fertilization, such a membrane 
 is formed immediately after the entrance of the first spermatozoon, a natural 
 inference being that this membrane may prevent the entrance of any more 
 spermatozoa. Biologists, however, are inclined to discredit the view that the 
 fertilization membrane is a protection against polyspermy. 
 
 Nothing is known in regard to fertilization of the human ovum. It has been 
 shown that in some of the lower Mammals fertilization regularly takes place 
 in the oviduct, and it is reasonable to assume that it occurs in the oviduct in 
 man. That spermatozoa can pass into and even all the way through the ovi- 
 
38 TEXT-BOOK OF EMBRYOLOGY. 
 
 duct is proved by cases of tubal, abdominal and, rarely, ovarian pregnancies. 
 On the other hand Wyder considers the uterus as the normal site of fertiliza- 
 tion, and some other gynecologists say that fertilization may take place in the 
 uterus. Waldeyer also concludes that fertilization may occur in the uterus. 
 
 Significance of Fertilization. 
 
 The meaning of such a widely occurring phenomenon as fertilization has 
 been interpreted differently by different scientists, and the question is still far 
 from definite solution. Its chief importance must be considered probably from 
 a standpoint of inheritance and is intimately associated with the interpretation 
 of the maturation processes of the germ cells (p. 25). There are, however, 
 several views which may be briefly mentioned. 
 
 The earlier belief that fertilization was a necessary antecedent to cleavage 
 of the ovum has been destroyed by the evidence of recent years. Loeb and 
 others have been able to induce artificial parthenogenesis in forms reproducing 
 normally by sexual reproduction. Thus cleavage has been started by chemical 
 stimulation in the eggs of many Molluscs, Echinoderms, Coelenterates, and 
 even in some of the lower Chordates (Teleosts and Amphibians). By fertilizing 
 pieces of egg-cytoplasm containing no nuclear material, parthenogenesis of the 
 sperm has likewise been produced. While cleavage produced in this manner 
 progresses only a short way, the evidence points to the conclusion that fertiliza- 
 tion is not an absolutely necessary factor in reproduction, although it normally 
 occurs in the great majority of cases. 
 
 Another view, advocated by Richard Hertwig and others, is that fertilization 
 induces a rejuvenescence of protoplasm. According to this view protoplasm 
 gradually passes into a state of senescence in which its activity is diminished. 
 With the admixture of new protoplasm during fertilization a new period of 
 vigorous activity is initiated. The life cycles of certain Protozoa are brought 
 to the support of this hypothesis. In these Protozoa a long period of reproduc- 
 tion by a series of cell divisions is followed by some form of conjugation. Two 
 individuals come together and an exchange of nuclear material takes place. 
 As a result a new impetus is given to the protoplasmic activity, and each of the 
 conjugants starts again on a long period of reproduction. It is highly probable 
 that the admixture of new protoplasm in fertilization among Metazoa produces 
 a similar invigorating effect. 
 
 Another interpretation of fertilization is that of Weissman who believed 
 that fertilization or "amphimixis" is important as a source of variation. Since 
 the chromatin of different individuals varies more or less, fertilization will pro- 
 duce new combinations and tend to the production of new forms. However, 
 there is very little evidence that forms which reproduce sexually show more 
 variations than those reproducing by parthenogenesis. 
 
FERTILIZATION. 39 
 
 References for Further Study. 
 
 COXKLIN, E. G.: The Embryology of Crepidula. Jour, of Morphol., Vol. XIII, 1897. 
 
 HARTMAN, C. G.: Studies in the Development of the Opossum. Jour, of M or ph., Vol. 
 XXVII, No. i, 1916. 
 
 HARPER, E. H.: The Fertilization and Early Development of the Pigeon's Egg. Am. 
 Jour, of Anat., Vol. Ill, No. 4, 1904. 
 
 HERTWIG, R.: Eireife, Befruchtung u. Furchungsprozess. In Hertwig's Handbuch d. 
 I'ergleich. u. experiment. Eniwickelungslehre der Wirbeltiere, Bd. I, Teil I, 1903. 
 
 HUBER, G. CARL: The Development of the Albino Rat. Memoirs of the Wistar Insti- 
 tute, No. 5, Philadelphia, 1915. 
 
 KELLICOTT, W. E.: General Embryology. New York, 1913. 
 
 KING, H. D.: The Maturation and Fertilization of the Egg of Bufo lentiginosus. Jour. 
 of Morphol., Vol. XVII, 1901. 
 
 LOEB, J.: Die Chemische Entwicklungserregung des Thierischen Eies. Berlin, 1909. 
 
 SOBOTTA, J.: Die Befruchtung u. Furchung des Eies der Maus. Arch. f. mik. Anal., 
 Bd. XLV, 1895. 
 
 WILSON, E. B.: The Cell in Development and Inheritance. 2d Ed., 1900. 
 
CHAPTER V. 
 
 CLEAVAGE (SEGMENTATION) . 
 
 Following fertilization and the commingling of male and female chromo- 
 somes, there occurs the usual longitudinal splitting of these chromosomes as in 
 ordinary mitosis. One-half of each chromosome now passes toward each 
 centrosome. The result is that one-half of each male chromosome and one- 
 half of each female chromosome enter into the formation of each of the two 
 new daughter nuclei (Fig. 22, 4, 5 and 6). The phenomena which follow are 
 apparently identical with those of ordinary mitosis and result in two similar 
 daughter cells. Each of the latter next undergoes mitotic division. In this 
 manner are formed four cells, eight cells, sixteen cells, and so on. This early 
 multiplication of cells which follows fertilization is known as cleavage or seg- 
 mentation of the ovum, the cells themselves are known as Uastomeres and the 
 cell mass as ihe^momla. 
 
 Important differences occur in the cleavage of eggs of different forms of 
 animals, due in large measure to the mechanical factors incident to variations 
 in the amount of yolk and its distribution within the egg. Upon this basis the 
 following classification of the forms of cleavage has been made. 
 
 FORMS OF CLEAVAGE. 
 
 a. Equal e.g., meiolecithal eggs of 
 
 Sponges, Echinoderms, some 
 Annelids, some Crustaceans, 
 some Mollusks, Amphioxus, 
 Mammals. 
 
 b. Unequal e.g., mesolecithal eggs of 
 
 Cyclostomes, Ganoid Fishes, 
 Ainphibians; usual type in 
 Annelids and Mollusks. 
 
 a. Superficial e.g., centrolecithal eggs 
 
 of Arthropods. 
 
 b. Discoidal e.g., polylecithal eggs of 
 
 Cephalopods, Bony Fishes, 
 Reptiles, Birds. 
 40 
 
 Holoblastic (complete or total) 
 
 Meroblastic (incomplete or partial) 
 
CLEAVAGE. 
 
 41 
 
 Holoblastic Cleavage. 
 
 (A) EQUAL. In this form of cleavage the entire egg divides and the cells 
 resulting from the early cell divisions are of approximately the same size. One 
 of the Echinoderms Synapta presents a beautiful example of this, the sim- 
 plest type of cleavage (Fig. 25). The egg of synapta is meiolecithal, contain- 
 ing very little yolk. The first cleavage is in a vertical plane at right angles to the 
 long axis of the central spindle and divides the egg into halves. The second 
 plane of cleavage is also vertical but is at right angles to the first cleavage plane 
 and results in four equal cells. The third cleavage plane is horizontal, cutting 
 the four cells resulting from the second cleavage into eight equal cells. The 
 fourth cleavage is vertical, the fifth horizontal and so on, regular alternation of 
 
 FIG. 25. Cleavage of the ovum of Synapta (slightly schematized). Selenka, Wilson. 
 A-E, Successive cleavages to the 32-cell stage. F, Blastula of 128 cells. 
 
 vertical and horizontal cleavage planes being continued through the ninth set 
 of divisions, resulting in 512 cells. At this point gastrulation begins and the 
 regularity of the cleavage planes is lost. Amphioxus is another classical ex- 
 ample of equal holoblastic cleavage, being classed as such, although after the 
 third cleavage the cells are not of exactly the same size. In Amphioxus the 
 first two cleavage planes are vertical and at right angles, as in Synapta. The 
 third cleavage plane is horizontal, as in Synapta, but the cells lying above the 
 third cleavage plane are smaller than those lying below it. The eight-cell stage 
 
42 TEXT-BOOK OF EMBRYOLOGY. 
 
 of Amphioxus thus presents four upper smaller cells and four lower larger 
 cells (Fig. 26). 
 
 The difference in size between the four upper and the four lower blastomeres 
 in Amphioxus finds probable explanation in the distribution of yolk within the 
 egg and the first four blastomeres. The yolk is greater in amount at the lower 
 pole of the cell, thus leaving the greater amount of protoplasm at the upper 
 pole. The nucleus tends to occupy the center of the protoplasmic mass and 
 consequently is nearer the upper pole. Therefore when the spindle forms 
 about the nucleus, the plane bisecting the spindle at right angles will be nearer 
 the upper pole of the cell. This plane corresponding to the division plane 
 of mitosis, the two resulting cells will be unequal in size, the smaller one 
 
 Micromeres 
 
 Segmentation 
 cavity 
 
 Macromeres 
 
 FIG. 26. Cleavage of the ovum of Amphioxus. Hatschek, Bonnet. 
 1-5, Lateral views of segmenting cells; 6, section of blastula. 
 
 lying above and the larger below. Thus is shown one of the effects of yolk 
 distribution. 
 
 (B) UNEQUAL. A good example of this form of cleavage is found in the 
 common frog's egg (Fig. 27). This egg while containing little yolk when com- 
 pared with such eggs as those of the fowl, contains much more yolk than does 
 the egg of Synapta or of Amphioxus. The frog's egg being a telolecithal egg, 
 the yolk is gathered at one pole, enabling a distinct differentiation to be made 
 between the upper darker protoplasmic or animal pole, and the lower lighter 
 vegetative pole (Fig. 6). The cleavage is complete but the cells which develop 
 at the yolk pole are much larger than those which develop at the protoplasmic 
 pole. The first and second cleavage planes are as in Synapta and Amphioxus, 
 vertical and at right angles to each other. Each of the four cells which result 
 from the second cleavage in the frog consists of a small upper darker protoplas- 
 mic pole and of a larger lower lighter yolk pole (Fig. 27, A). The nuclear 
 
CLEAVAGE. 
 
 43 
 
 elements lying, as they always do, within the protoplasmic portion of the cell, 
 determine the next cleavage plane which is horizontal and lies nearer the proto- 
 plasmic ends of the cells. The result is that the third cleavage gives rise to 
 eight cells, four of which are small protoplasmic cells lying above the line of 
 cleavage, while the other four are large yolk-containing cells which lie below 
 the line of cleavage (Fig. 27, A). This distinction between protoplasmic cells 
 
 B 
 
 D 
 
 H 
 
 I 
 
 FIG. 27. Cleavage of the frog's egg. Morgan. 
 
 A, Eight-cell stage; B, beginning of sixteen-cell stage; C, thirty-two-cell stage; D, forty-eight-cell 
 stage (more regular than usual); E, F, G, later stages; H, I, formation of blastopore. 
 
 and yolk cells not only persists but tends to become more and more marked as 
 segmentation proceeds, and it soon becomes evident that the cells unencum- 
 bered by yolk have a tendency to segment more rapidly than do their yolk- 
 laden brethren (Fig. 27, C, D, E, F and G). Thus, while the fourth cleavage 
 is vertical in both types of cells, giving rise to eight upper protoplasmic cells 
 and the same number of lower yolk cells, this uniformity of number persists 
 
44 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 only up to this point, while beyond this point the protoplasmic cells increase in 
 number much more rapidly than do the yolk cells, so that when the protoplasmic 
 cells number 128, there are still but comparatively few yolk cells. There thus 
 result in total unequal cleavage, cells of two very different sizes each confined 
 to its own part of the segmenting cell mass. 
 
 Meroblastic Cleavage. 
 
 (A) SUPERFICIAL. This form of cleavage is seen in the centrolecithal eggs 
 of Arthropods. These eggs consist of a central mass of nutritive yolk sur- 
 
 c d 
 
 FIG. 28. Cleavage in hen's egg. Coste. Germinal disk and part of yolk, seen from above. 
 
 rounded by a comparatively thin layer of protoplasm. The segmentation 
 nucleus lies in the middle of the nutritive yolk where it undergoes the usual 
 mitotic divisions. The resulting daughter nuclei leave the central yolk mass 
 and pass out into the peripheral layer of protoplasm where they apparently 
 
CLEAVAGE. 45 
 
 determine segmentation of the protoplasm, the number of protoplasmic seg- 
 ments corresponding to the number of nuclei. There is thus formed a super- 
 ficial layer of cells (blastomeres) enclosing the central nutritive yolk. 
 
 (B) DISCOIDAL. This type of cleavage occurs in eggs which have an ex- 
 cessive amount of yolk and in which the protoplasm is confined to a small super- 
 ficial germ disk. The telolecithal ova of Birds furnish typical examples of this 
 form of cleavage. The first cleavage plane is vertical and divides the proto- 
 plasmic disk into halves. The second cleavage plane is also vertical and at 
 right angles to the first, resulting in four approximately equal cells (Fig. 28, a). 
 The third cleavage plane is also vertical, dividing two of the four cells (Fig. 28, 
 b). The germ disk at the end of the third cleavage consists of six pyramidal 
 cells lying with their apices together in the center of the germ disk, their bases 
 lying peripherally and toward the yolk mass. They are separated from one 
 another at the surface, but are still continuous below and peripherally with the 
 
 y.s. g.a. s.c. w.y. 
 
 FIG. 29. From a vertical section through the germ disk of a fresh-laid hen's egg. Duval, Herturig. 
 g.d., Upper layer of germ disk; s.c., segmentation cavity; w.y., white yolk (see Fig. 7); y.s., lower 
 layer of germ disk (yolk cells, merocytes). 
 
 underlying yolk mass and consequently with each other. The analogy be- 
 tween this condition and that described for the frog's egg is complete with the 
 one exception that in the latter the cleavage furrows cut completely through 
 the yolk cells or the yolk-containing portions of the cells, while in the bird's egg 
 the amount of yolk is so great that the cleavage furrow merely passes a short 
 distance into it without completely dividing it into segments. The fourth 
 cleavage plane is tangential, cutting off the apices of the six pyramidal segments. 
 The germ disk after the fourth cleavage thus consists of six small superficial 
 central cells and six larger cells which surround the small cells and also separate 
 the latter from the underlying yolk. From this point radial and tangential 
 cleavages follow each other without any semblance of regularity. The result 
 is a mass of small cells lying at the center of the disk and surrounded by larger 
 cells (Fig. 28, c, d). The smaller cells are completely separated from the under- 
 lying yolk while the larger cells are for a time continuous with it (Fig. 29). 
 Comparing the unequal holoblastic cleavage of the frog's egg with discoidal 
 
46 TEXT-BOOK OF EMBRYOLOGY. 
 
 meroblastic cleavage as seen in the eggs of Birds, it becomes immediately evi- 
 dent that the differences between them are explainable entirely by reference to 
 the greater quantity of yolk in the bird's egg. The real activity of segmenta- 
 tion is in both cases confined almost wholly to the protoplasm. In the frog's 
 egg the amount of yolk present is sufficient to impede segmentation in the 
 larger cells but not to prevent it. In the bird's egg the amount of yolk is so 
 great that it cannot be made to undergo complete segmentation. 
 
 Reviewing the results of cleavage, it is to be noted that in every case there is 
 formed a larger or a smaller group of cells. In the case of equal holoblastic 
 cleavage, these cells are all of the same or of nearly the same size, and constitute 
 
 Micromeres. 
 
 mz 
 
 Macromeres. 
 
 FIG. 30. From a sagittal section through blastula of frog. Bonnet, 
 mz., Marginal zone. 
 
 what is known as the morula or mulberry mass (Fig. 25, E). A similar condition 
 obtains in unequal holoblastic cleavage with the one exception, that there is a 
 marked difference in the size of the cells constituting the morula (Fig. 27). In 
 superficial meroblastic cleavage the group of cells forms a layer enclosing the 
 central yolk, the latter being unsegmented but containing some nuclei. In 
 discoidal meroblastic cleavage the group of cells spreads itself over a limited 
 superficial area, while beneath it lies the large mass of unsegmented yolk, con- 
 taining, however, some nuclei (Figs. 28 and 29). 
 
 In holoblastic cleavage the blastomeres in the interior of the mass become 
 more or less separated during segmentation, a cavity thus being formed within 
 the so-called morula. This cavity increases in size, the cells being pushed 
 centrifugally, and the embryo soon consists of a layer or layers of cells enclosing 
 
CLEAVAGE. 
 
 a cavity, the segmentation cavity. The entire embryo is now known as the 
 blastula. 
 
 The simplest type of blastula is seen in Amphioxus, where it consists of a 
 nearly spherical segmentation cavity surrounded by a single layer of cells. 
 Some of the cells those which are more ventral and contain the larger amount 
 of yolk are slightly larger than others (Fig. 26, 6). 
 
 In the eggs of the frog, in which the cells resulting from segmentation show 
 greater inequality in size (due to difference in yolk content), the segmentation 
 cavity is surrounded by several layers of cells. In such a blastula the roof of 
 the cavity is comparatively thin, being composed of small cells containing little 
 yolk, micromeres, while the floor of the cavity is thick, being composed of large 
 
 FIG. 31. Four stages in cleavage of the ovum of the mouse. Sobotta 
 Small cell marked with x is the polar body. 
 
 :olk cells, macromeres. So thick is this wall of the vegetative pole of the blastula 
 that the large yolk cells extend into the segmentation cavity compressing it into 
 a crescentic cleft (Fig. 30). In the frog the roof of the segmentation cavity is 
 sharply denned from the floor, due to the fact that the outer layer of cuboidal 
 roof cells is densely pigmented. The rather sharply defined zone of transition 
 between pigmented micromeres and nonpigmented macromeres is known as the 
 marginal zone. 
 
 In discoidal segmentation, the segmentation cavity is a mere slit between the 
 superficial protoplasmic cells and the underlying unsegmenting yolk with its 
 yolk nuclei (Fig. 29). Comparing it with unequal holoblastic cleavage, these 
 partially divided yolk cells which form the floor of the segmentation cleft in 
 discoidal cleavage are analogous to the large yolk cells which form the floor of 
 the segmentation cavity in the frog. (Compare Figs. 29 and 30.) 
 
48 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 In the mammalian ovum, as in the other cases just described, segmentation 
 leads up to the formation of a solid mass of cells the morula. While cleavage 
 here is of the holoblastic equal type, the irregularity is especially marked. In 
 the mouse, for example, the second cleavage is complete in one of the blasto- 
 meres before it has begun in the other, so that a three-celled stage results 
 (Fig. 31). Following this is a four-celled stage. From this time on cleavage 
 continues irregularly until a solid mass is formed, as in the lower forms, which 
 is composed of apparently similar cells (Fig. 32). 
 
 The next step in mammalian development is a differentiation of the super- 
 ficial layer of the cells of the morula. The result, then, is a single surface layer, 
 the covering layer, surrounding a central mass of polygonal cells (Fig. 33, a). 
 This solid mass of cells is transformed into a vesicle by vacuolization of some of 
 
 Subzonal 
 
 space 
 
 Morula 
 
 FIG. 32. Morula of rabbit, van Beneden. 
 
 the inner cells (Fig. 33) and the confluence of these vacuoles to form a cavity. 
 The mammalian ovum at this stage thus consists of two groups of cells and a 
 cavity, an outer group or layer of cuboidal cells, the outer cell layer or covering 
 layer (trophoderm), forming the wall of the cavity, and an inner group of poly- 
 gonal or spheroidal cells, the inner cell mass which at one point is attached to 
 the outer layer of cells (Fig. 33, d). 
 
 The mistake must not, however, be made of considering the mammalian 
 ovum at this stage as a true blastula. The mammalian ovum apparently does 
 not pass through any true blastula stage. Of the parts just described, the inner 
 cell mass alone is comparable to the blastoderm of birds, while the cavity cor- 
 responds not to the segmentation cavity but to the yolk mass of meroblastic 
 eggs. The vacuolization of the cells of the inner cell mass would thus repre- 
 sent a late and abortive attempt at yolk formation, the actual nutritive yolk 
 being made unnecessary, since the attachment of the ovum to the walls of the 
 uterus provides for direct parental nutrition. In the separation of the cells of 
 the morula into an inner cell mass and an outer covering layer is seen the earliest 
 
CLEAVAGE. 
 
 49 
 
 differentiation into cells (inner cell mass), which are destined to form the 
 embryo proper, and cells (outer cells covering layer) which are to engage in 
 the development of certain accessory structures. 
 
 Recent studies of opossum ova (Hartman) have shown that in this form the 
 morula stage is absent. During segmentation the blastomeres migrate periph- 
 erally and form a single layer of cells around a central cavity, although a few 
 cells usually remain free within the cavity. At about the 4o-celled stage the 
 majority of the cells forming the wall of the hollow structure (blastocyst) begin 
 
 
 1 
 
 FIG. 33. Four stages in the development of the bat. van Beneden. 
 
 a, Section of morula; b, section of later stage of morula, showing differentiation of outer layer of 
 cells; c, section of still later stage, showing vacuolization of central cells; d, section showing outer 
 layer (trophoderm) and inner cell mass. 
 
 to diminish in thickness, while a few at one point increase in thickness. The 
 latter proliferate to form a little mass which probably corresponds to the inner 
 cell mass described for the bat. The layer of thin cells forming the major 
 portion of the wall of the blastocyst may be considered as comparable with the 
 covering layer in the bat. The cells in each region are probably lineal descend- 
 ants of one or the other of the two primary blastomeres, although the latter 
 exhibit no distinguishing features; one blastomere gives rise to embryonic 
 structures proper and the other to extraembryonic or accessory structures. 
 
50 TEXT-BOOK OF EMBRYOLOGY. 
 
 v 
 
 In the albino rat (Huber) cleavage gives rise to a true morula consisting of 
 from 24 to 32 cells. Subsequent to this there appears among the cells of the 
 morula a crescentic space which gradually enlarges until the cells, being pushed 
 peripherally, form a relatively thin layer around a central cavity. At one point 
 in the wall of this hollow structure (blastocyst, blastodermic vesicle) a little 
 mass of cells constitutes the probable homologue of the inner cell mass which 
 has been described previously. 
 
 References for Further Study. 
 
 ASSHETON, R.: The Segmentation of the Ovum of the Sheep, with Observations on the 
 Hypothesis of a Hypoblastic Origin for the Trophoblast. Quart. Jour, of Mic. Science, Vol. 
 XLI, 1898. 
 
 BLOUNT, M.: The Early Development of the Pigeon's Egg, with Especial Reference to 
 the Supernumerary Sperm Nuclei, the Periblast and the Germ Wall. Biolog. Bull., Vol. 
 XIII, No. 5, 1907. 
 
 CONKLIN, E. G.: Karyokinesis and Cytokinesis. Jour. Acad. Nat. Sci. of Philadelphia, 
 Vol. XII, 1902. 
 
 CONKLIN, E. G.: The Embryology of Crepidula. Jour, of MorphoL, Vol. XIII, 1897. 
 
 EYCLESHYMER, A. C.: The Early Development of Amblystoma, with Observations on 
 Some Other Vertebrates. Jour, of MorphoL, Vol. X, 1895. 
 
 HARPER, E. H.: The Fertilization and Early Development of the Pigeon's Egg. Am. 
 Jour, of Anat., Vol. Ill, No. 4, 1904. 
 
 HARTMAN, C. G.: Studies on the Development of the Opossum. Jour, of Morph., Vol. 
 XXVII, 1916. 
 
 HATSCHEK, B.: Studien iiber Entwickelung des Amphioxus. Arbeiten aus dem zool. 
 Instit. zu Wien, Bd. IV, 1881. 
 
 HERTWIG, R.: Eireife, Befruchtung u. Furchungsprozess. In Hertwig's Handbuch d. 
 vergleich. u. experiment. Entwickelungslehre der Wirbeltiere, Bd. I, Teil I, 1903. 
 
 HUBER, G. CARL: The Development of the Albino Rat. Memoirs of the Wistar Institute, 
 No. 5, 1915. 
 
 LILLIE, F. R.: The Development of the Chick. New York, 1908. 
 
 MORGAN, T. H.: The Development of the Frog's Egg. New York, 1897. 
 
 SOBOTTA, J.: Die Befruchtung u. Furchung des Eies der Maus. Arch. f. mik. Anat., 
 Bd. XLV, 1895. 
 
 VAN BENEDEN, E.: Recherches sur les premiers stades du developpement du Murin 
 (Vespertilio murinus). Anat. Anz., Bd. XVI, 1899. 
 
 WILSON, E. B.: The Cell in Development and Inheritance. 2d Ed., 1900. 
 
CHAPTER VI. 
 
 GERM LAYERS.* 
 
 THE TWO PRIMARY GERM LAYERS FORMATION OF THE GASTRULA. 
 Gastrulation in Amphioxus. 
 
 The changes which immediately follow the formation of the blastula can be 
 observed in their simplest form in Amphioxus, where, it will be remembered, 
 the blastula is a hollow sphere the wall of which consists of a single layer of cells 
 which enclose the segmentation cavity (Fig. 26,6). Gastrulation begins by a 
 flattening of the ventral wall of the blastula (Fig. 34, A). This is followed by 
 a folding in or imagination of the yolk cells which form the ventral wall (Fig. 
 34, B). These cells press upward into the segmentation cavity which they soon 
 completely obliterate, and come to lie immediately beneath and in contact with 
 the smaller cells which had formed the roof of the cavity (Fig. 34, C). 
 
 The gastnda, as the embryo is now called, thus consists of two layers of cells 
 which lie in close apposition and enclose the new cavity, the archenteron (ccelen- 
 teron primitive gut) formed by the imagination (Fig. 34, C and D). This 
 cavity remains open externally, the opening being known as the blastopore 
 (Fig. 34, C and D) . These two layers of cells which form the wall of the gastrula 
 are the primary germ layers. The outer layer is known as the ectoderm or 
 epiblastj the inner layer as the entoderm or hypoblast. As seen by reference to 
 Fig. 34, C and D, the two primary germ layers are directly continuous with each 
 other at the blastopore. 
 
 The most significant feature of the transformation of the blastula into the 
 gastrula is that whereas in the blastula all the cells are essentially similar, 
 differing if at all only in the amount of yolk contained, in the gastrula two dis- 
 tinct types of cells are recognizable. The cells of the outer layer differ from 
 those of the inner layer both structurally and functionally. Thus in some of the 
 lowest forms the gastrula stage is the adult stage. In such the outer cells are 
 protective, react to external stimuli, develop cilia which determine locomotion, 
 etc. The inner cells, on the other hand, are more especially concerned with 
 nutrition, absorbing food, and giving off waste products. Von Baer's apprecia- 
 
 * For many of the ideas contained in this chapter, especially the correlation of gastrulation and 
 the formation of the mesoderm in different forms, the writers are indebted to Bonnet's excellent de- 
 scription in his "Lehrbuch der Entwickelungsgeschichte." 
 
 The homologizing of gastrulation in the different forms has been found the most satisfactory 
 method of teaching the subject. At the same time it must be admitted that some of the correlations 
 are not based on actual observations. 
 
 51 
 
52 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 tion of the significance of this first cell differentiation is evidenced by the fact 
 that he designated the two primary germ layers the "primitive organs" of the 
 body. 
 
 It should be noted that with the completion of gastrulation certain important 
 landmarks in adult topography have been established. Thus the animal 
 
 Segmentation cavity 
 
 Micromeres 
 
 Segmentation cavity 
 
 Macromeres 
 
 Invagination 
 
 C 
 
 Archenteron 
 
 Blastopore 
 
 Anterior lip of blastopore 
 
 Blastopore 
 
 Post, lip of 
 blastopore 
 
 Ectoderm Entoderm Ectoderm Entoderm 
 
 FIG. 34. Gastrulation in Amphioxus. Hatschek, Bonnet. 
 
 (micromere) pole is always the dorsum; the vegetative (macromere) pole 
 always the ventrum; the blastopore, being always caudal, differentiates the 
 tail end from the head end of the embryo. 
 
 Gastrulation in Amphibians. 
 
 This is modified as compared with gastrulation in Amphioxus by the 
 presence of a greater amount of yolk. A clear understanding of the modifica- 
 tions which this increased yolk content causes in the gastrulation of Amphibians, 
 
GERM LAYERS. 
 
 53 
 
 as well as of Reptiles and Birds, is essential to a proper appreciation of the 
 process in Mammals. 
 
 Recalling the amphibian blastula (p. 47), it will be remembered that its 
 roof was formed of smaller protoplasmic cells (micromeres) while its floor con- 
 sisted of a mass of yolk cells which encroached upon the segmentation cavity 
 
 Micromeres 
 
 Marginal 
 zone 
 
 Macromeres 
 
 FIG. 35. Vertical section through b'.astula of Triton. Hertwig. 
 
 (Fig. 30). The zone of union between the two kinds of cells is known as the 
 marginal zone. The simplest type of amphibian gastrulation, and the type 
 thus most easily compared with gastrulation in Amphioxus, is exemplified by 
 the water salamander Triton taeniatus. (Compare Figs. 34 and 35.) 
 
 Ectoderm 
 Entoderm 
 
 Anterior lip of blastopore 
 
 Blastopore 
 
 Posterior lip of blastopore 
 
 Yolk cells 
 (entoderm) 
 
 Segmenta- 
 tion cavity 
 
 FIG. 36. Vertical section through embryo of Triton, showing beginning of gastrulation. Hertwig. 
 
 In Triton, a slight groove or furrow appearing along a portion of the marginal 
 zone marks the blastopore and the beginning of gastrulation. The upper lip 
 of this groove is formed by the smaller protoplasmic cells, the low r er by the large 
 yolk cells (Fig. 36). The groove next deepens, the micromeres growing in at 
 the dorsal lip to form the roof of the archenteron, while the yolk cells are carried 
 
54 TEXT-BOOK OF EMBRYOLOGY. 
 
 over the ventral lip to form the floor. The imagination cleft which thus be- 
 comes the archenteron is at first small as compared with the segmentation cavity 
 but rapidly increases in size, until as in Amphioxus, the earlier cavity is finally 
 completely obliterated (Fig. 37). Coincident with the carrying of the yolk 
 cells into the interior of the vesicle and the obliteration of the segmentation 
 cavity, proliferation of the micromeres carries them completely around the yolk 
 cells, so that the entire surface of the gastrula is formed of small cells (Fig. 37). 
 The amphibian gastrula thus consists of a central cavity, the archenteron, 
 communicating with the exterior by means of a small opening, the blastopore, 
 the roof of the cavity being formed by two or more layers of small cells, the 
 floor by the mass of large yolk cells. The outer layer of cells completely sur- 
 rounds the yolk cells except at the blastopore, and constitutes the ectoderm 
 (Fig. 37). The inner layer or entoderm is distinct only in the roof of the cavity. 
 Laterally its cells pass over without any distinct demarcation into the mass of 
 
 Ectoderm 
 
 Entoderm (protentoderm) 
 
 Archenteron 
 
 Yolk cells (yolk entoderm) 
 Peristomal mesoderm 
 
 Yolk plug 
 
 Posterior lip of blastopore 
 
 Peristomal 
 mesoderm 
 
 FIG. 37. Vertical section through gastrula of Triton. Hertwlg. 
 
 yolk cells which form the floor of the cavity. As the ectoderm forms a com- 
 plete outer layer, the only point at which the yolk cells now appear externally is 
 the blastopore, into which they project as the yolk plug (Fig. 37). 
 
 It is possible in the amphibian gastrula to make the distinction between the 
 entoderm of the roof which has grown in from the surface and is continuous 
 with the surface ectoderm, and the entoderm of the floor which is formed of yolk 
 cells. By those who make this distinction, the former is called the protentoderm t 
 the latter the yolk entoderm (Fig. 37). 
 
 In the case of the common frog, the eggs of which are so easily obtained 
 that they furnish most satisfactory subjects for study, gastrulation is somewhat 
 less simple than in Triton. As already noted (p. 47) the demarcation between 
 micromeres and macromeres is in the frog very distinct, owing to the dark pig- 
 mentation of the former. This is shown in Fig. 30, as is also the fact that the 
 roof of the segmentation cavity consists of a surface layer of strongly pig- 
 
GERM LAYERS. 55 
 
 merited cells, and beneath this a layer of less pigmented cells. Fig. 38 shows 
 the beginning of gastrulation, being a slightly earlier stage than the Triton 
 gastrula (Fig. 36). 
 
 In the frog (also in the toad and salamander) a modification of the comple- 
 tion of gastrulation occurs, which, while apparently unimportant, is considered 
 by some investigators as having significance hi the interpretation of gastrulation 
 in higher forms, especially in Mammals. It is illustrated in Fig. 39. The 
 wedge-shaped mass of yolk cells is pushed in front of the invagination cleft and 
 carried around dorsally just beneath the ectoderm (Fig. 39, ft). This is met hi 
 the medial dorsal plane by yolk cells which have grown up from the floor of the 
 segmentation cavity on the opposite side (Fig. 39, c). What was the segmenta- 
 
 Cells with 
 much pigment 
 
 ,^^^^^___ ^^^^^^^ Cells yrith 
 
 Micromeres -M * ^B 5^ less pigment 
 
 Macromeres 
 
 Invagination (blastopore) 
 FIG. 38. From sagittal section of blastula of frog, showing beginning of gastrulation. Bonnet. 
 
 tion cavity thus becomes divided into a cleft beneath the ectoderm and a cavity 
 surrounded by yolk cells. The cavity is designated by Bonnet the " Erganzungs- 
 hohle" or "completioti cavity" (Fig. 39, c, d t e). With continued enlargement 
 of the invagination cavity, the cleft-like remains of the segmentation cavity 
 beneath the ectoderm becomes obliterated and the "completion cavity" becomes 
 pressed ventrally. The wall between the latter and the invagination cavity 
 thins and finally ruptures so that the two cavities become one. 
 
 It thus happens that at one stage there are three cavities (Fig. 39, d) (i) 
 the slit-like remains of the segmentation cavity, (2) the invagination cavity and 
 (3) the so-called "completion cavity." The remains of the segmentation 
 cavity is seen by reference to the figures to lie between the ectoderm externally 
 and the protentoderm and yolk entoderm internally. The invagination cavity 
 
56 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 is limited mainly by protentoderm, the "completion cavity" by yolk entoderm. 
 The breaking of the partition between the invagination cavity and the "com- 
 pletion cavity'' results in the formation of the archenteron proper or primitive 
 gut, which is thus lined partly by protentoderm and partly by yolk ento- 
 
 Ectoderra 
 
 "Wedge" 
 
 Ectoderm 
 
 "Wedge" 
 
 <- Ectoderm - 
 
 Segment. 
 
 cav. 
 "Wedge" 
 
 Blastopore 
 Peristomal 
 mesoderm 
 
 Blastopore 
 
 Yolk plug 
 
 Ectoderm 
 
 Ectoderm 
 
 Protentoderm 
 
 Protentoderm 
 
 Ant. lip of 
 blastopore 
 
 Yolk plug 
 
 Post, lip of 
 blastopore 
 
 FIG. 39. Successive stages of gastrulation in the frog, showing especially the formation of the 
 protentoderm, yolk entoderm and "completion cavity." Schultze, Bonnet. Com.pl., "Completion 
 plate." 
 
 derm, the two being from now on called simply entoderm. The somewhat 
 thickened area of yolk cells at the junction of the protentoderm and yolk 
 entoderm is designated by Bonnet, the "Erganzungsplatte" or "completion 
 plate" (Fig. 39, d, e). 
 
GERM LAYERS. 
 
 57 
 
 Gastrulation in Reptiles and Birds. 
 
 This is further modified by the still greater increase in yolk, yet retains 
 sufficient similarity to the process in Amphibians and Amphioxus to allow of 
 comparison. 
 
 FIG. 40. Surface view of blastoderm of snake. Hertu'ig. Blastopore is represented by dark 
 transverse band near lower side of figure. 
 
 In the types of gastrulation thus far described in Amphioxus, Triton and 
 the frog the entire egg is involved in segmentation and gastrulation. Up 
 through these forms there is a progressive increase in the amount of yolk, which 
 
 Embryonic disk 
 
 Blastoderm 
 
 Anterior lip 
 
 Posterior lip 
 of blastopore 
 
 Blastopore 
 (crescentic groove) 
 
 FIG. 41. Surface view of embryonic disk of turtle (Emys taurica). Bonnet. 
 X, The lighter shading represents the opacity due to the growth of the protentoderm (see Fig. 42). 
 
 in Triton and still more in the frog was seen to modify the gastrulation process. 
 In the reptilian and the avian ovum there is a much greater increase in yolk 
 content, the segmentation being confined to the germ disk and to a small part of 
 
58 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 the underlying yolk (p. 56). Just as cleavage in Reptiles and Birds was 
 modified by the presence of the large unsegmenting yolk mass, so, for the same 
 
 Ectoderm of embryonic disk 
 
 Blastopore 
 
 Ectoderm 
 
 Yolk entoderm 
 Blastopore 
 
 Ectoderm 
 
 'Completion 
 plate" 
 
 Protentoderm 
 
 Yolk entoderm 
 
 Blastopore 
 
 Peristomal mesoderm 
 
 Peristomal 
 Blastopore mesoderm 
 
 "Completion 
 plate" 
 
 Remnant of 
 protentoderm 
 
 Blastopore 
 
 Peristomal 
 mesoderm 
 
 "Completion plate" Yolk entoderm 
 
 FIG. 42. From medial vertical sections through embryonic disk of lizard, showing five successive 
 stages in gastrulation. Wenckebach, Bonnet. 
 
 reason, is gastrulation quite modified, as compared with the simple process seen 
 in Amphioxus. At the same time, however, it is possible to correlate the reptil- 
 ian and avian gastrulation with gastrulation in the lower forms. 
 
GERM LAYERS. 
 
 59 
 
 Area apaca 
 Area pellucida 
 
 Blastopore 
 ~ (crescentic 
 groove) 
 
 It will be remembered that in the discoidal cleavage of Birds the blastula 
 consists of a cleft-like segmentation cavity, the roof of which is formed by the 
 proliferating micromeres constituting the germ disk, while the floor is formed by 
 the partially segmenting yolk (Tig. 29). The former corresponds to the micro- 
 meres of the blastula roof in Amphioxus and Amphibians, the latter to the 
 underlying yolk cells. (Compare Figs. 26, 6, 30 and 29.) 
 
 In Reptiles the beginning of gastrulation is 
 evidenced by the appearance of an opacity just in 
 front of what may now be designated the posterior 
 margin of the disk (Fig. 40). This is due to more 
 rapid proliferation of cells at this point. The 
 opacity soon shows a depression or groove which 
 more or less sharply defines the posterior margin 
 
 of the disk. It varies in shape in different Rep- . FlG - 43- Surface view of blasto- 
 derm of unincubated hen s egg. 
 
 tiles. It is frequently crescent-shaped and has Hertwig. 
 been called the crescentic groove (Fig. 41). This 
 
 groove is the blastopore, and corresponds to the blastoporic invagina- 
 tions of Amphioxus, Triton and the frog. Soon after the formation of the 
 crescentic groove, there appears in front of it an oval opacity which extends 
 forward in the medial line (Fig. 41). This opacity is due to growth of cells 
 forward from the blastopore under the surface cells as seen in Fig. 42 which 
 shows the progress of the invagination in the lizard. These figures should be 
 
 compared with Figs. 34, 36 and 37, 
 showing the stages of gastrulation in 
 Amphioxus and Triton, and especially 
 with Figs. 38 and 39 showing gastrula- 
 tion in the frog. 
 
 In Fig. 42, i, the blastopore is seen 
 as a distinct invagination. As in the 
 frog (Fig. 39) the invagination pushes 
 in front of it a wedge-shaped mass of 
 cells which extends forward under the 
 outer layer. These cells are the pro- 
 tentoderm. They form the roof and, 
 with the underlying yolk entoderm, the 
 floor of the new invagination cavity 
 
 (Fig. 42, 2). As they extend forward they meet with a thickened part of 
 the yolk entoderm, the " Erganzungsplatte " or "completion plate" (Fig. 42, 
 2, 3, 4 and 5; compare Fig. 39). There are thus present at this stage, just 
 as in the frog, three cavities, (i) the slit-like remains of the segmentation 
 cavity, (2) the invagination cavity and (3) the "completion cavity." Also 
 5 
 
 p.b. a.b. 
 
 y.c. 
 
 FIG. 44. From vertical longitudinal section 
 through germ disk of siskin, showing beginning 
 of gastrulation. Duval. 
 
 a.b., Anterior lip of blastopore; arc., archen- 
 teron; ec., ectoderm; en., entoderm; p.b., posterior 
 lip of blastopore; y., white yolk; y.c., yolk cells 
 (merocytes). 
 
60 TEXT-BOOK OF EMBRYOLOGY. 
 
 as in the frog (Fig. 39), by a breaking through of the two layers the pro- 
 tentoderm and the yolk entoderm which separate the invagination cavity 
 from the " completion cavity" in Fig. 42, 2, the two cavities are united to form 
 the archenteron or primitive gut (Fig. 42, 3, 4 and 5). The single-layered germ 
 disk has thus become transformed into a two-layered disk consisting of an outer 
 (upper) layer the ectoderm and an inner (lower) layer the entoderm 
 (protentoderm). 
 
 In Birds the gastrula is formed in a manner quite comparable with its forma- 
 tion in Reptiles. Taking the hen's egg as an example, it will be remembered 
 that the entire segmentation area is confined to the germ disk, and that this con- 
 sists of a superficial layer (roof of segmentation cavity) of small well defined 
 cells (micromeres) beneath which is the cleft-like segmentation cavity, while the 
 floor of this cavity is formed of incompletely segmented yolk (Fig. 29). The 
 beginning of gastrulation is marked by the appearance of a crescentic bar near 
 the posterior margin of the disk. This bar is due to more rapid proliferation 
 of the cells in this region, and in it there appears the crescentic groove or blasto- 
 
 y.c. a.b. arc. ec. en. 
 
 FIG. 45. From vertical longitudinal section through two-layered germ disk of nightingale. Hertwig. 
 a.b., anterior lip of blastopore; arc., archenteron; ec., ectoderm; en., entoderm (protentoderm); y.c., 
 yolk cells (merocytes.) 
 
 pore (Fig. 43). Just as described in lower forms, especially Reptiles, the 
 micromeres invaginate or fold under at this point and grow forward as the 
 protentoderm, and roof in the new cavity formed by the invagination (Fig. 44). 
 The single-layered germ disk is thus transformed into a two-layered disk con- 
 sisting of an outer (upper) layer the ectoderm and an inner (low r er) layer 
 the entoderm (protentoderm). The protentoderm in a sense replaces the 
 original layer of yolk cells in the area where the invagination occurs; the original 
 outer layer (micromeres) becomes the ectoderm, except that portion which is 
 invaginated to form the protentoderm (Fig. 45). This process is comparable 
 with the disappearance of the yolk entoderm in Reptiles (Fig. 42). At the same 
 time the segmentation cavity is obliterated and the new cavity invagination 
 cavity which is in communication with the exterior, appears beneath the 
 protentoderm. (Compare Figs. 42 and 45.) 
 
 Under the central portion of the germ disk the yolk becomes liquefied, 
 while at the margin of the disk it continues to segment and give rise to large 
 nucleated cells the yolk entoderm. This is known as the area of supplemental 
 
GERM LAYERS. 
 
 61 
 
 cleavage and apparently corresponds to the " Erganzungsplatte " or " com- 
 pletion plate" described in lower forms (p. 56; see also Figs. 39 and 42). 
 The germ disk continues to spread out over the yolk and at the same time the 
 area of liquifying yolk increases. The portion of the disk above the liquified 
 yolk appears translucent on surface view and is known as the area pellucida; 
 the more peripheral part of the disk is less transparent, being more closely 
 attached to the unchanged yolk, and is known as the area opaca. 
 
 Area opaca 
 
 Hensen's node 
 
 Primitive streak 
 
 Area pellucida 
 "Completion plate' 
 Head process 
 
 Primitive groove 
 
 Post. Hp of 
 blastopore 
 
 FIG. 46. Surface view of embryonic disk of chick. Bonnet. 
 
 There next appears in front of the crescentic groove and extending from its 
 middle point forward in the medial line, a linear opacity which is known as the 
 primitive streak (Fig. 46). This ends anteriorly in a knob-like expansion 
 Hensen's node. According to Duval, Hertwig, Bonnet and others, the primi- 
 tive streak is formed in the following manner. A notch or indentation appears 
 in the anterior lip of the transverse blastoporic slit (Figs. 43 and 47, A). As 
 
 Area opaca 
 t Area pellucida 
 
 Primitive streak 
 
 Area pellucida 
 Area opaca 
 Primitive streak 
 
 Blastopore 
 (crescentic groove) 
 
 FIG. 47. Surface views of blastoderms of Haliplana, showing formation of primitive streak. 
 
 Schauinsland. 
 
 the germ disk is constantly spreading in all directions, if the apex of this notch 
 remains fixed, the extension of the disk posteriorly must result in a drawing out 
 of the notch into a longitudinal slit (Fig. 47, B). In other words, the horns of 
 the crescentic slit are pushed together to form a longitudinal slit. And as the 
 two lips of the slit come together they fuse, and the line of fusion is marked by a 
 shallow groove, the primitive groove. At the anterior end of the slit in the region 
 
62 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 of Hensen's node, there is a small area where fusion does not occur, thus leaving 
 a small opening which communicates with the cavity of the primitive gut. Since 
 the primitive groove is formed from the original crescentic slit, and the original 
 crescentic slit is the blastopore, the primitive groove may be considered as a 
 modified blastopore in which the only opening is at Hensen's node. The 
 primitive groove lies in the medial line of the primitive streak; and since the 
 primitive groove is a modified blastopore, the two primary germ layers are fused 
 
 ec. en. arc. 
 
 Lb. y.p. 
 
 FIG. 48. From transverse section through Hensen's node germ disk of chick of 2 to 6 hours' incu- 
 bation. Duval. For lettering see FIG. 49. 
 
 at the lips of the primitive groove (Figs. 48 and 49). To this fusion is due the 
 opacity which constitutes the primitive streak as seen from the surface (Fig. 46). 
 After the formation of the primitive groove and streak there is no longer any 
 specially marked definition of the posterior margin of the germ disk, the entire 
 circumference having a uniform demarcation. 
 
 Very soon after the formation of the primitive streak a new opacity appears 
 which extends forward in the medial line from Hensen's node (anterior lip of 
 the blastopore). This is known as the head process, or "primitive intestinal 
 
 en. ec. p.g. 
 
 FIG. 49. From transverse section through primitive groove germ disk of chick of 2 to 6 hours' incu- 
 bation. Duval. 
 
 arc., Archenteron; ec., ectoderm; en., entoderm; 7.6., lip of blastopore; p.g. } primitive groove; y. t 
 yolk; y.p., yolk plug. 
 
 cord" (Bonnet) (Fig. 50). This new opacity is due to growth of cells under the 
 ectoderm, the cells constituting the protentoderm. As a matter of fact, this 
 formation of the protentoderm is a further extension of that same process 
 which began with the crescentic groove (blastopore) invagination and continued 
 during the transformation of the crescentic groove into the primitive streak 
 (still the blastopore). Consequently this whole process from the formation of 
 the crescentic groove up entirely through the formation of the protentoderm, is 
 
GERM LAYERS. 63 
 
 homologous with the simpler protentoderm formation from the crescentic 
 groove (blastopore) in Reptiles. (Compare Fig. 51 with Fig. 42.) As the 
 protentoderm grows forward in the medial line it apparently replaces the yolk 
 entoderm, so that the roof of the new cavity the archenteron is formed of 
 protentoderm. The area where the protentoderm fuses with the yolk entoderm 
 is, as in Reptiles, the "completion plate." 
 
 The only real difference between gastrulation in Reptiles and in Birds is 
 that in Birds the crescentic groove (original blastopore) becomes transformed 
 into the primitive groove which remains open only at its anterior end (Hensen's 
 node) , while in Reptiles the blastopore may be of any form, crescentic, round, oval, 
 etc., but does not usually present a longitudinal linear appearance. Thus in the 
 latter case the primitive intestinal invagination (the head process, "primitive 
 
 _ "Area opaca 
 Area pellucida 
 
 "Completion plate* 
 
 Hensen's node 
 Primitive streak 
 
 Head process 
 
 FIG. 50. Surface view of chick blastoderm. Bonnet. 
 
 intestinal cord") grows forward from the original point of invagination near the 
 posterior margin of the disk. 
 
 Gastrulation in Mammals. 
 
 Reference to the description of segmentation in the mammalian ovum and 
 its peculiarities (p. 48) makes it evident that these peculiarities must deter- 
 mine further modifications in the development of the germ disk as compared 
 with lower forms. It will be remembered that segmentation in the mamma- 
 lian ovum had been carried to the differentiation of two kinds of cells (p. 48), 
 an outer cell layer (trophoderm) and an inner cell mass (Fig. 33). In lower 
 forms the first cell differentiation came with the formation of the two primary 
 germ layers, the ectoderm and the entoderm, and these with the enclosed cavity 
 constituted the gastrula. The first cell differentiation in Mammals has, how- 
 ever, an entirely different significance, the trophoderm having nothing to 
 do with the formation of the embryo but being destined to give rise to extra- 
 embryonic structures. It is the cells of the inner cell mass or embryonal bud 
 
64 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 which give rise to the embryonic structures proper. In 
 other words, the inner cell mass alone is the anlage of 
 the embryo and this at this stage shows no differentiation 
 into germ layers (Fig. 33). 
 
 The initial step in the formation of the two primary 
 germ layers in the mammalian ovum is the differentia- 
 tion and splitting off of the deeper cells of the inner 
 cell mass (Fig. 52, a). These cells are the primitive 
 entoderm and, as a single layer, soon extend around 
 the vesicle until they completely line it. They lie in 
 apposition to the cells of the trophoderm except where 
 separated from them by the remaining cells of the inner 
 cell mass. While the primitive entoderm is extending 
 around the vesicle, vacuolization of the more superficial 
 cells of the inner cell mass takes place (Fig. 52, b) and 
 results in the formation of a cavity between the over- 
 lying trophoderm and the still remaining cells of the 
 inner cell mass. This cavity is known as the amniotic 
 cavity (Fig. 52, c). Its roof is formed by the tropho- 
 derm, w T hile its floor is formed by the remaining cells 
 of the inner cell mass, which have now become arranged 
 in a distinct layer and constitute the embryonic disk 
 (Fig. 52, c). The latter lies directly upon the primary 
 entoderm and constitutes the surface layer of the 
 embryo the ectoderm. Thus at this stage of develop- 
 ment, the roof of the amniotic cavity is composed of 
 cells which are to give rise to extraembryonic structures, 
 or envelopes, while the floor is composed of the two- 
 layered embryo now consisting of ectoderm and ento- 
 derm. Those investigators who attempt to homologize 
 the early differentiation of cells in Mammals and in 
 lower forms, consider this first formed entoderm in 
 Mammals as identical with the yolk entoderm of lower 
 forms and so designate it, although it does not consist 
 of yolk cells. The protentoderm is formed later (p. 66). 
 
 Considering as a specific example gastrulation in 
 the dog, it is to be noted that just before gastrulation 
 begins, the embryonic disk of the dog is essentially 
 similar to that of the bat which has been described 
 (see above), with the exception that in the dog the 
 embryonic disk is not roofed in by the amnion. At 
 
GERM LAYERS. 
 
 65 
 
 the stage corresponding to Fig. 52, c, the embryonic disk of the dog presents on 
 surface view a uniform appearance. 
 
 The first differentiation noticeable in the disk is an opacity at what now 
 becomes defined as the posterior margin of the disk (Fig. 53). As the em- 
 
 FIG. 52. Sections of blastodermic vesicle of bat, showing (a) formation of the entoderm an 3 
 (b and c) of the amniotic cavity, van Beneden. 
 
 bryonic disk increases in size a linear opacity appears extending from the 
 opacity at the posterior margin of the disk forward in the medial line to a point 
 somewhat anterior to the center of the disk. The appearance (Fig. 53) is 
 strikingly similar to that of the chick at the same stage (Fig. 46). The posterior 
 opacity corresponds to the crescentic groove, the linear opacity to the primitive 
 
66 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 streak, its anterior club-shaped end to Hensen's node. If we assume the same 
 transformation of the crescentic groove into the primitive groove, the two to- 
 gether corresponding to the blastopore, the condition is quite analogous to that 
 in the chick (p. 61). 
 
 At a slightly later stage than shown in Fig. 53, a new opacity appears ex- 
 tending forward in the medial line from Hensen's node (Fig. 54, a). This is 
 the head process, and may be considered as homologous with the head process in 
 the chick. (Compare Fig. 54, a, with Fig. 50.) The opacity is due to a plate 
 or cord of cells which grows from the region of Hensen's node forward under the 
 surface layer of cells (ectoderm) (Fig. 55). On the assumption that Hensen's 
 
 Si 
 
 Embryonic disk 
 
 Hensen's node *,'*; 
 
 FIG. 53. Embryonic disk of dog. Bonnet. The letters and figures on the right (Si-S 4 ) indicate 
 
 planes of sections shown in Fig. 75. 
 
 node is the anterior lip of the blastopore, this plate of cells may possibly be con- 
 sidered as homologous with the invaginated cells which form the protentoderm 
 in Reptiles and Birds. (Compare Figs. 42, 51 and 55.) Consequently, since 
 the protentoderm in the lower forms was designated the "primitive intestinal 
 cord" (Urdarmstrang), so in Mammals this invaginated cord of cells maybe 
 called the "primitive intestinal cord" (protentoderm) (Fig. 54). 
 
 In Reptiles it has been seen that as the protentoderm grows forward under 
 the surface layer (ectoderm) the yolk entoderm for some distance disappears, 
 and the protentoderm fuses with the remaining yolk entoderm in an area 
 known as the completion plate (Fig. 42). In the chick also it has been stated 
 that a similar process occurs (p. 62). In Mammals the yolk entoderm, which 
 
GERM LAYERS. 
 
 67 
 
 Embryonic disk 
 Hensen's node 
 
 Primitive streak 
 
 and groove 
 
 Embryonic disk 
 
 Completion plate 
 
 I Head process 
 
 Prim. int. cord 
 (protentoderm) 
 
 w 
 
 Ectoderm 
 
 Yolk entoderm 
 
 Ectoderm 
 
 
 Si 
 
 Yolk entoderm 
 
 Ectoderm 
 
 Mesoderm 
 
 Completion plate 
 
 Medullary folds 
 
 Yolk entoderm 
 
 Yolk entoderm 
 
 Chordal plate (protentoderm) 
 Primitive groove 
 
 Mesoderm 
 
 Mesoderm 
 
 Mesoderm 
 
 Mesoderm 
 
 Mesoderm 
 
 Yolk entoderm 
 
 FIG. 54. Surface view of embryonic disk of dog and transverse sections of same "Bonnet, 
 a, Disk somewhat further advanced than that in Fig. 53; the letters and figures (Si-S 5 ) indicate planes 
 of sections in b. m. gr., medullary groove. 
 
68 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 was present from the time of its differentiation from the inner cell-mass (Fig. 52), 
 apparently disappears or is replaced by the protentoderm, as the latter grows 
 forward under the ectoderm and finally the protentoderm becomes continuous 
 at its anterior border with the yolk entoderm that remains. The area where the 
 two become continuous is the "completion plate" (Fig. 55). 
 
 The disappearance of the yolk entoderm, or its replacement by protentoderm, 
 occurs, however, only in a linear area; that is, the protentoderm grows forward 
 only as a narrow band of cells which replaces a correspondingly narrow band of 
 
 Mesoderm Blastopore 
 
 Embryonic disk 
 
 Ectoderm 
 
 Mesoderm 
 
 Yolk entoderm Chordal plate Completion plate 
 
 Fro. 55. Medial section of germ disk of bat. van Beneden. 
 
 yolk entoderm. And since this strip of protentoderm is destined to give rise to 
 the notochord, it is sometimes known as the "chordal plate" (Fig. 54, S 3 ). 
 From the manner of formation of the " chordal plate," it is continuous along 
 each side with the yolk entoderm (Fig. 54, S 2 ). 
 
 No human ovum showing gastrulation has been observed. What is known 
 of the formation of the germ layers in man is discussed on p. 85. 
 
 FORMATION OF THE MIDDLE GERM LAYER MESODERM. 
 
 Mesoderm Formation in Amphioxus. In such a simple type as Amphi- 
 oxus the formation of the middle germ layer is readily observed and there is 
 consequently no question as to the manner in which it arises. In higher forms, 
 however, the origin of the mesoderm has been and still continues to be one of 
 the most difficult of embryological problems. 
 
 In the two-layered Amphioxus gastrula the mesoderm first appears as two 
 symmetrical evaginations of the entoderm which push out dorso-laterally from 
 the archenteron (Fig. 56, a). That part of the entoderm which lies between the 
 two mesodermic evaginations is composed of somewhat higher cells than those 
 of the developing mesoderm and constitutes the anlage of the notochord (chorda). 
 The lips of the mesodermic evaginations next come together (Fig. 56, b) in such a 
 manner that the mesoderm becomes completely separated from the archenteron 
 (Fig. 56, c). While this separation is taking place, the mesodermic evaginations 
 divide transversely into a number of segments which lie on each side of the 
 medial line and are known as the mesodermic somites primitive segments 
 (Fig. 57). Meanwhile, the chorda anlage is being transformed into the chorda 
 
GERM LAYERS. 
 
 69 
 
 itself. This transformation is initiated by an evagination dorsalward of the 
 entodermic cells which lie between the two mesodermic evaginations (Fig. 56, c), 
 these cells soon becoming constricted off as the solid cord of cells which consti- 
 tute the notochord (Fig. 56, d). With the separation of the chorda, the remain- 
 ing entoderm unites across the medial line and becomes the epithelium (en- 
 toderm) of the primitive intestine. The formation of the mesodermic somites 
 begins near the middle of the embryo and proceeds caudally. There is thus at 
 this stage a row of somites on each side of the medial line, the number of somites 
 
 Notochord 
 
 Mesodenn 
 Notochord 
 
 Entoderm 
 
 Parietal 
 mesoderm 
 Visceral 
 mesoderm 
 
 Intestine 
 Entoderm 
 
 FIG. 56. From transverse sections through Amphioxus embryos, showing successive stages in for- 
 mation of mesoderm, neural tube and notochord. Bonnet. 
 
 increasing by constant differentiation and pushing forward of more segments 
 (somites) from the caudal unsegmented mesoderm (Fig. 57). 
 
 While the above described changes have been taking place, those ectodermic 
 cells which lie along the dorsal medial line become higher and form the bottom 
 of a shallow longitudinal groove. This is known as the neural groove, while the 
 folds which bound the groove on each side are known as the neural folds (Fig. 
 56, a). From the crests of the folds the remaining lower ectodermic cells grow 
 across and meet in the medial line thus forming the surface ectoderm (Fig. 56, 
 b and c). The neural groove next deepens, the neural folds bending dorsally 
 
70 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 and toward the medial line where they finally meet, thus converting the groove 
 into a closed canal or tube, the neural tube (Fig. 56, d; see Chap. XVII). As the 
 ectoderm grows over the neural groove and as the latter becomes transformed 
 into the neural tube, there remains anteriorly an opening from the exterior into 
 
 Anterior (cephalic) end 
 
 Epidermis 
 (ectoderm) 
 
 Entoderm 
 
 Coelom 
 (myocoel) 
 
 Archenteron 
 
 Unsegmented 
 mesoderm 
 
 Posterior (caudal) end 
 
 FIG. 57. From horizontal section through Amphioxus embryo with 5 primitive segments; seen from 
 
 dorsal side. Hatschek. 
 
 The communication between the cavities of the primitive segments (coelom) and the archenteron 
 can be seen in the last 4 segments. 
 
 the neural tube. This is known as the neuropore (Fig. 58) . Caudally, the neural 
 groove extends over the region of the blastopore and as the groove closes over to 
 form the neural tube, it embraces the blastopore which now becomes closed 
 
 Neuropore 
 
 Primitive segment 
 Coelom (myocoel) 
 
 Intestine 
 
 Epidermis (ectoderm) 
 Neural tube 
 
 Anterior ) lip of 
 Posterior j blastopore 
 
 Unsegmented 
 mesoderm 
 
 FIG. 58. From vertical section through Amphioxus embryo with 5 primitive segments. Hatschek. 
 
 externally but opens into the neural tube. This opening, which thus connects 
 the neural tube with the intestine, is known as the neurenteric canal (Fig. 58), 
 and it is a rather remarkable fact that while giving rise to no adult organ, it is 
 found without exception in all Vertebrates which have been studied. 
 
GERM LAYERS. 71 
 
 The mesodermic somites meanwhile extend their edges ventrally between 
 the ectoderm and the entoderm until they meet and fuse in the midventral line 
 (Figs. 56, d and 59). A transverse constriction next appears which cuts off the 
 ventral extension. The latter is known as the lateral plate, w r hile the remaining 
 dorsal part is still designated the primitive segment. (Compare Fig. 56, d } with 
 
 Fig. 59)- 
 
 The primitive segments retain their segmental character. The lateral 
 plates, on the other hand, do not retain their segmented condition but fuse, their 
 cavities uniting to form the primitive body cavity or ccelom, which is the anlage 
 of the large serous cavities of the adult. The outer part of the lateral plate or 
 
 Neural tube 
 
 ^ Notochord 
 
 Epidermis (ectoderm) 
 
 ^^JS/^>^t^Q"\ m^^^ 
 
 ' Primitive segment 
 
 Muscle plate 
 Cutis plate 
 Myocoel 
 
 Splanchnocoel 
 
 Parietal mesoderm ~) 
 
 Mat. plate 
 Entoderm -W^^^H^S/^ Visceral mesoderm J 
 
 Ventral Subintestinal 
 mesentery vein 
 
 FIG. 59. Diagram to show differentiation of primitive segment into muscle plate (myotome) and 
 cutis plate and relation of myocoel and splanchnocoel. Bonnet. Compare with Fig. 56, d. 
 
 parietal mesoderm, with the adjacent ectoderm, forms the somatopleure (Fig. 59). 
 The inner layer of the lateral plate, the visceral mesoderm, with the adjacent 
 entoderm, forms the splanchnopleure (Fig. 59). 
 
 At the caudal end of the embryo, just in front of the neurenteric canal, there 
 exists at this stage an area where the germ layers have not become differentiated 
 to form special structures. In this area, cell proliferation is especially active and 
 from it cells are derived for the completion of the neutral tube, chorda, somites, 
 intestine, etc. By this means the growth of the embryo in length is provided 
 for (Figs. 57 and 58). 
 
 The Amphioxus embryo at this stage thus consists of: 
 
 1. Ectoderm. Surface ectoderm and neural tube. 
 
 2. Mesoderm. Somites; parietal mesoderm and visceral mesoderm 
 
 enclosing the ccelom. 
 
 3. Entoderm. Chorda and wall of primitive intestine. 
 
72 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 Mesoderm Formation in Amphibians. In Amphibians the formation of 
 the mesoderm is, like gastrulation, modified by the presence of many large yolk 
 cells. Taking for an example the water salamander (Triton), which furnishes 
 
 Blastopore 
 
 Ectoderm 
 Parietal mesoderm 
 
 Visceral mesoderm 
 
 Entoderm 
 
 Primitive gut 
 FIG. 60. From transverse section through Triton embryo at region of blastopore. Hertwig. 
 
 perhaps the simplest type of mesoderm formation in Amphibians, only in the 
 region of the blastopore does the mesoderm formation conform at all closely to 
 that of Amphioxus. In this region the middle germ layer is seen to consist of 
 two lateral evaginations which push out between the entoderm and ectoderm, 
 
 Notochord anlage Neural plate 
 
 Parietal mesoderm 
 Visceral mesoderm 
 
 Primitive gut 
 Entoderm 
 
 FIG. 61. From transverse section through Triton embryo in front of blastopore. Hertwig. 
 
 each containing a cavity, the primitive body cavity (Fig. 60). More cranially 
 the mesoderm grows out laterally between the entoderm and ectoderm, not as 
 two hollow evaginations, but as solid plates of cells which only later separate into 
 two layers and enclose the primitive body cavity (Fig. 61). Hertwig considers 
 
GERM LAYERS. 
 
 73 
 
 mesoderm formation in Triton entirely analogous to its formation in Amphioxus, 
 the solid plate of cells being really two layers enclosing the body cavity, but 
 pressed together by the large amount of yolk. Although the mesoderm de- 
 veloped in the region of the blastopore and that which originates more cranially 
 are continuous in front of the blastopore, it is convenient to designate the 
 former the peristomal, the latter the gastral mesoderm. 
 
 The separation of the mesoderm into a dorsal segmented part and a ventral 
 unsegmented part containing the body cavity; the formation of the notochord 
 between the two lateral plates of mesoderm by a constricting off of cells from the 
 entoderm; the closure of the primitive intestine beneath the notochord; the 
 development of the neural groove and folds with their final closure to form the 
 neural tube; and the extension of ectoderm over their surface to form the surface 
 ectoderm (epidermis), are processes quite similar to the formation of the same 
 
 Myocoel 
 
 Xeural 
 tube 
 
 Coelom 
 
 Primitive segment 
 
 mesoderm 
 
 Yolk cells 
 (entoderm) 
 
 FIG. 62. From transverse section through dorsal part of Triton embryo. Hertwig. 
 
 structures in Amphioxus (Fig. 62). Also as in Amphioxus, the differentia- 
 tion of these structures is more advanced cranially and gradually extends 
 caudally where for some time there exists a growth area in which they are not as 
 yet differentiated. 
 
 In the frog the formation of the mesoderm is sufficiently different from 
 Amphioxus and Triton to make its correlation somewhat difficult. In the frog 
 apparently all trace of mesodermic evagination is lost. Taking a transverse 
 section through the frog's gastrula at a stage when the blastopore is still circular 
 and widely open (Fig. 39), the mesoderm is seen as a flat plate of cells which 
 blends in the medial line with the protentoderm and ventrally with the yoke 
 entoderm (p. 74, Fig. 63). The mesoderm has here arisen apparently by a 
 splitting off of a layer of cells from the protentoderm, the remaining cells of the 
 protentoderm forming the roof of the primitive gut. Beginning at the sides, the 
 
74 TEXT-BOOK OF EMBRYOLOGY. 
 
 separation of the mesoderm extends dorsally to the chorda and ventrally, as 
 indicated by arrows in Fig. 63, splitting off the superficial cells of the yolk 
 entoderm until the mesoderm becomes completely separated from the yolk cells. 
 On each side of the notochord the mesoderm shows a shallow longitudinal groove 
 (Fig. 64) which has been interpreted by some as the homologue of the meso- 
 dermic evagination of Amphioxus. This groove does not persist, however, and 
 has nothing to do with the formation of the body cavity. The latter in the frog 
 results not from evagination but from a splitting of the originally solid mesoder- 
 mic plates. It is to be noted, however, that while the ccelom does not originate 
 as an evagination from, and is never connected with, the primitive intestine, 
 the mesoderm itself consists of cells which have split off from the wall of the 
 
 Chorda anlage 
 
 f Ectoderm 
 
 Yolk entoderm 
 
 Remnant of 
 segmentation cavity 
 
 FIG. 63. Transverse section of embryo of frog (Rana fusca). Bonnet. The section is taken in front 
 
 of (anterior to) the blastopore. 
 
 primitive intestine (entoderm), and that it is within this group of cells that the 
 ccelom finally appears. Of the yolk cells, only the outermost (most peripheral) 
 have to do with the formation of intestinal epithelium, the remainder being 
 ultimately used up for the nutrition of the embryo (Fig. 65). 
 
 The formation of the neural groove and neural tube from the ectoderm and 
 the separation of the chorda anlage from the rest of the entoderm are much the 
 same as in Triton. 
 
 Mesoderm Formation in Reptiles and Birds. The actual origin of 
 the mesoderm in these forms is very difficult to determine owing to the pecu- 
 liarities of gastrulation which in turn are due to the greatly increased amount 
 of yolk. In the lower forms it has been seen that the mesoderm is primarily a 
 derivative of the entoderm (Amphioxus, Fig. 56), or of protentoderm and yolk 
 
GERM LAYERS. 
 
 75 
 
 entoderm (frog, Fig. 53). One would expect, a priori, that the mesoderm has 
 a similar origin in the higher forms, even if the entoderm has assumed a differ- 
 ent form on account of the fact that the yolk plays little or no part in the process 
 
 Ectoderm 
 
 Mesoderm 
 
 Chorda anlage 
 
 Entoderm 
 
 FIG. 64. Transverse section through dorsal part of embryo of frog (Rana fusca). Ziegler. 
 x, Groove indicating evagination to form mesoderm. 
 
 of imagination. As a matter of fact, observations do to a certain extent fulfill 
 the expectation, but, on the other hand, it is not possible to trace the earliest 
 steps in its formation with anything like the degree of certainty with which it 
 can be traced in the lower forms. 
 
 Neural crest 
 
 Neural canal 
 
 Primitive segment 
 
 Notochord 
 
 Coelom 
 
 Ventral mesoderm < 
 
 Yolk cells 
 
 ? Ectoderm 
 
 Parietal mesoderm 
 Visceral mesoderm 
 
 Entoderm 
 
 FIG. 65. Transverse section through embryo of frog (Rana fusca). Bonnet. 
 
 Taking the chick again as an example, the mesoderm appears first in the 
 region of the primitive groove (blastopore). Transverse sections through this 
 region show the mesoderm as several layers of small irregular cells interposed 
 laterally between the ectoderm and entoderm. In the medial line, or line of the 
 
76 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 primitive groove, all three germ layers are blended into a solid mass of cells 
 (Fig. 66) . On the ground that the primitive groove is the blastopore, the meso- 
 derm here is the peristomal mesoderm, the homologue of the peristomal 
 mesoderm which encircles the blastopore in lower forms (Fig. 37). 
 
 Primitive groove and folds 
 
 Ectoderm 
 
 Ectoderm 
 
 Mesoderm 
 
 Entoderm 
 
 FIG. 66. Transverse sections of blastoderm of chick (21 hours' incubation). Hertwig. 
 
 a, Section through primitive groove, posterior to Hensen's node. 
 
 b, Section through Hensen's node. 
 
 At a somewhat later stage, after the head process appears, sections through 
 the head process also show all three germ layers. Here the ectoderm is a sepa- 
 rate layer; but the entoderm and mesoderm are fused in the medial line; that 
 
 Head process Neural plate 
 
 Ectoderm 
 Mesoderm 
 Entoderm 
 
 Yolk cell - 
 
 Archenteron 
 
 Yolk 
 
 FIG. 67. Transverse section of blastoderm of chick (21 hours' incubation). Hertwig. Section 
 through head process, anterior to Hensen's node. 
 
 is, in the line of the "primitive intestinal cord." Laterally, the layers are all 
 separate, a cleft existing between the mesoderm and the ectoderm and another 
 between the mesoderm and the entoderm (Fig. 67). Since the mesoderm in 
 the region of the head process is in front of the primitive groove (blastopore) 
 
GERM LAYERS. 77 
 
 and appears in connection with the " primitive intestinal cord/' it is the gastral 
 mesoderm, the homologue of the gastral mesoderm described in lower forms 
 (Fig. 63). Here also, as in the case of the peristomal mesoderm, the mesoderm 
 is primarily a solid plate of cells. Furthermore, immediately in front of the 
 primitive groove the gastral mesoderm is continuous with the peristomal. 
 
 At a still later stage the gastral mesoderm is found to be separated from the 
 entoderm, so that the "primitive intestinal cord" (now the notochord) separates 
 the mesoderm of the two sides in the medial line (Fig. 68). 
 
 Neural plate Xotochord 
 
 ' Ectoderm 
 ' Mesoderm 
 
 :-" ' Entoderm 
 "" " Archenteron 
 
 FIG. 68. Transverse section of blastoderm of chick (40 hours' incubation). Hertwig. 
 Section taken short distance anterior to Hensen's node. 
 
 Comparing the conditions in sections through the head process in the chick 
 with sections through the body region of the frog (Figs. 63 and 64), a fairly 
 clear homology may be drawn. 
 
 While in the stages just described in the chick the mesoderm is present and 
 interposed between the ectoderm and entoderm, the crucial point is its actual 
 origin. In the lower forms it originated from the entoderm, that is, from the 
 cells which have been invaginated at the blastopore. In the chick the blasto- 
 pore ; which is crescent-shaped, is transformed into a longitudinal structure 
 
 Mesoderm Primitive groove 
 
 _ FIG. 69. Transverse section of blastoderm of chick (10 hours' incubation). Hertwig. 
 Section taken through primitive groove and streak. 
 
 the primitive groove but still the blastopore. As the crescentic blastopore 
 becomes longitudinal, the two horns come together and fuse (see p. 61), and 
 the line of fusion still represents the area of imagination, where some of the 
 surface cells have grown under the remaining surface cells to form the entoderm 
 (protentoderm) . And it is along this area of invagination that the mesoderm 
 first appears. In very early stages there is an especially active cell proliferation 
 in the thickened layer of cells which represents the primitive streak. This 
 activity gives rise to a mass of cells which lie immediately beneath the primitive 
 
78 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 groove and represent the first mesodermal cells (Fig. 69). It is reasonable to 
 assign the origin of these cells to the cells which have been invaginated along the 
 line of the primitive groove (blastopore). These invaginated cells constitute 
 the protentoderm, hence the mesodermal cells may be considered as derivatives 
 of the protentoderm. 
 
 As proliferation continues, the mesodermal cells spread out between the 
 ectoderm and entoderm (which is here yolk entoderm) (Fig. 70). Finally, the 
 
 Ectoderm p.gr. 
 
 Mesoderm 
 
 Ectoderm 
 
 Entoderm 
 
 Yolk 
 
 FIG. 70. Transverse section of blastoderm of chick (slightly older than that shown in Fig. 69). 
 
 Hertwig. 
 Section taken through primitive groove (p.gr.) and streak. 
 
 mesoderm fuses with the yolk entoderm, so that all three germ layers are fused 
 beneath the primitive groove (Fig. 66). The fusion between the mesoderm and 
 yolk entoderm in this region is a secondary matter. 
 
 That the peristomal mesoderm is a derivative of the invaginated cells is 
 even more clearly demonstrated in Fig. 71, in which the two lips of the blasto- 
 pore have not yet fused. 
 
 Primitive fold Primitive groove 
 
 FIG. 71. Transverse section through primitive streak and primitive groove of Diomedea. 
 
 Schauinsland. 
 
 In front of the primitive groove, that is, in the region of the head process, the 
 gastral mesoderm is at first seen to be continuous with the "primitive intestinal 
 cord" (Fig. 67); later it becomes separated on each side from the "primitive 
 intestinal cord" (now the notochord). While the actual process has not been 
 observed, it is reasonable to assume that the mesoderm is here also a derivative 
 of the "primitive intestinal cord," and since the latter is produced by the in- 
 vagination (gastrulation, see p. 62) and consists of protentoderm, the gastral 
 
GERM LAYERS. 
 
 79 
 
 mesoderm is a derivative of the protentoderm or invaginated cells. Also, as the 
 invagination is a continuous process from the first formation of the crescentic 
 
 Ectoderm 
 
 Neural 
 tube 
 
 Entoderm 
 
 Ccfclom 
 
 FIG. 72. Transverse section of chick embryo (2 days incubation). Photograph. 
 The parietal mesoderm (lying above the ccelom) is not labeled. The two large vessels under 
 the primitive segments are the primitive aortae. Spaces separating germ layers are due to 
 
 shrinkage. 
 
 groove up through the formation of the ''primitive intestinal cord" (see p. 62), 
 one can readily understand how the mesoderm is first formed in the line of the 
 primitive groove and continues to be formed progressively forward as the invagi- 
 
 Area pellucida 
 Area vasculosa 
 
 Head fold 
 Neural groove 
 
 Primitive segment 
 Primitive groove 
 
 FIG. 73. Dorsal view of duck embryo, with two pairs of primitive segments. Bonnet. 
 
 nation pushes farther and farther forward to form the "primitive intestinal 
 cord." The gastral mesoderm is thus from its beginning continuous with the 
 peristomal mesoderm, the two together forming a single plate of cells. 
 
80 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 As described above, the mesoderm of the chick is at first a solid plate of cells. 
 The cavity in the mesoderm the ccelom appears as the result of a splitting 
 of the originally solid mesoderm layer into two sublayers the parietal and the 
 visceral (Fig. 72). At the same time that portion of the mesoderm which lies 
 adjacent to the neural groove on both sides of the medial line becomes differen- 
 tiated into two series of bilaterally symmetrical segments the primitive seg- 
 ments, which are connected with one another by intermediate thinner parts 
 (Figs. 73, 74 and 72). The splitting of the mesoderm to form the ccelom begins 
 some distance from the medial line and progresses both laterally and medially. 
 
 Neuropore 
 
 Fore-brain vesicle 
 
 Head fold 
 
 Proamnion 
 
 Mid- and hind- 
 brain vesicles 
 
 Edge of 
 blastoderm 
 
 Neural fold 
 
 Primitive 
 groove 
 
 FIG. 74. Dorsal view of chick embryo with ten pairs of primitive segments. Bonnet. 
 
 The ccelom does not, however, reach the primitive segments, for a small solid 
 mass of cells the intermediate cell mass (Fig. 81) always intervenes between 
 the ccelom and the segments. Furthermore, the ccelom from the beginning 
 shows no segmentation. 
 
 The formation of the neural groove and neural tube from the ectoderm and 
 the separation of the chorda anlage from the entoderm are much the same as in 
 the frog. A decided difference is, however, to be noted in the shape of the 
 chick's blastoderm. Since in this case the yolk plays but a small part in seg- 
 mentation, the germ layers at first lie flat upon the surface of the yolk, the 
 
GERM LAYERS. 
 
 81 
 
 archenteron being a flat cavity between the entoderm and the yolk (Figs. 67, 68 
 and 69) . The tubular form of the intestine is brought about later in connection 
 with the constriction of the embryo from the yolk sac (p. 136; see also forma- 
 tion of primitive gut, p. 316). 
 
 Mesoderm Formation in Mammals. In Mammals the same difficulties 
 are met with in determining the origin of the mesoderm as in the chick. At the 
 same time, transverse sections through the developing mammalian blastoderm 
 
 Si 
 
 Mesoderm 
 
 Yolk Completion 
 entoderm plate 
 
 Pr.int.co. 
 
 P.gr. Ectoderm 
 
 I 
 
 Yolk entoderm Pr.st. 
 
 FIG. 75. Transverse sections of embryonic disk of dog. Bonnet. 
 
 Sections of disk shown in Fig. 53. Letters and numbers at right (Sj-S^ indicate plane of sections 
 in Fig. 53. P.gr., Primitive groove; Pr.int.co., primitive intestinal cord; Pr.st., all three 
 germ layers fused in primitive streak. 
 
 at different stages show conditions which bear much resemblance to those in the 
 chick, and lead toward the conclusion that the processes in the two cases are 
 much alike. 
 
 Referring back to gastrulation, it will be remembered that on surface view 
 the germ disks of the chick and of the dog were very similar (compare Fig. 46 
 with Fig. 53, and Fig. 50 with Fig. 54, a). After the formation of the primitive 
 streak in the dog, sections through this region show the mesoderm interposed 
 between the ectoderm and entoderm (here yolk entoderm) and all three germ 
 
82 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 layers fused beneath the primitive groove (Fig. 75, S 3 and(S 4 ; compare with 
 Fig. 66). The origin of the mesoderm is probably, as in the chick, to be at- 
 tributed to the invaginated cells (protentoderm) along the line of the primitive 
 groove. The mesodermal cells first appear as a small mass beneath the primi- 
 tive groove (Fig. 76, a) ; they then spread out laterally between the ectoderm and 
 (yolk) entoderm (Fig. 76, b). Beneath the point of origin, that is, along the 
 
 Primitive streak Entoderm Mesoderm Ectoderm 
 
 FIG. 76. Transverse sections of embryonic disks of rabbit, (a) Kdlliker, (b) Rabl. 
 a, section through primitive streak of embryo of 6 days and 18 hours; b, section through Hensen's 
 node of embryo of 7 days and 3 hours. 
 
 line of the primitive groove, they finally fuse with the (yolk) entoderm (Figs. 
 75, S 3 and S 4 ; compare Figs. 76, a and b, and Figs. 75, S 3 and S 4 with Figs. 69, 
 70 and 66). 
 
 In the region of the head process, as in the chick, sections show at first the 
 entoderm and mesoderm fused in the medial line, and the ectoderm as a sepa- 
 rate layer (Fig. 77 and Fig. 75, S 2 ). The entoderm with which the mesoderm is 
 
 Mesoderm Notochord 
 
 Ectoderm 
 
 Entoderm 
 
 FIG. 77. Transverse section of embryonic disk of rabbit, van Beneden. 
 
 fused represents the invaginated cells, that is, the protentoderm ("primitive 
 intestinal cord"); and, as in the chick, it seems reasonable to assume that the 
 mesoderm is derived from the " primitive intestinal cord " (protentoderm) and 
 grows out laterally between the ectoderm and entoderm (compare Fig. 75, S 2 
 with Fig. 67). 
 
 A little later, in the region of the head process, the mesoderm on each side is 
 
GERM LAYERS. 
 
 83 
 
 found to be separated from the parent tissue ("primitive intestinal cord"), and 
 the latter now represents the anlage of the notochord (compare Fig. 72 with 
 Fig. 78). 
 
 On the ground that the primitive groove is the blastopore, the mesoderm 
 arising in that region is the peristomal mesoderm; that arising from the 
 "primitive intestinal cord'* in front of the primitive groove is the gastral meso- 
 
 Mesoderm Ectoderm Neural groove 
 
 Yolk entoderm Chordal plate 
 
 FIG. 78. Transverse section of embryonic disk of dog. Bonnet. 
 Section taken near anterior end of head process. 
 
 derm. The peristomal and gastral portion together constitute a continuous 
 plate of cells interposed between the ectoderm and entoderm, which has been 
 derived from the invaginated cells of the protentoderm. 
 
 In a few Mammals (sheep, roe, shrew), mesoderm has been seen to arise 
 some distance from the primitive streak and head process (Fig. 79). This has 
 been called the peripheral mesoderm, but it soon unites with the peristomal and 
 gastral. 
 
 Embryonic disk 
 I 
 
 Peripheral 
 mesoderm 
 
 Ectoderm 
 
 Area of 
 nvagination 
 
 Nuclei of 
 yolk entoderm 
 
 FIG. 79. Surface view of embryonic disk of sheep. Bonnet. 
 Disk is at that stage of development when gastrulation begins (in region marked area of imagination). 
 
 Primarily, the mesoderm is a solid plate of cells with no indication of a body 
 cavity (ccelom). A little later the mesoderm splits into two layers, the parietal 
 and the visceral, between which lies the ccelom (Fig. 81). The splitting does 
 not effect, however, the mesoderm which lies adjacent to the neural groove on 
 both sides of the medial line, for this portion becomes differentiated into two 
 series of bilaterally symmetrical segments the primitive segments (Figs. 80 and 
 
84 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 *" 
 
 Prim, pericard. 
 
 cavity 
 
 Anlage / 
 of heart * 
 
 Tail fold 
 of amnion 
 
 Telencephalon 
 Diencephalon 
 Mesencephalon 
 
 Metencephalon 
 Myelencephalon 
 
 Peripheral limit 
 of coelom 
 
 IK 
 
 FIG. 80. Dorsal view of dog embryo with ten pairs of primitive segments. Bonnet, 
 
 Prim. Intermed 
 seg. cell mass 
 
 Parietal and 
 visceral mesoderm 
 
 Ectoderm 
 (epidermis) 
 
 Chordal Prim, 
 plate aorta 
 
 Ccelom Entoderm Blood vessels 
 81. Transverse section of dog embryo with ten pairs of primitive segments. Bonnet. 
 
GERM LAYERS. 
 
 85 
 
 8r). The splitting of the mesoderm begins some distance from the medial line 
 and proceeds both laterally and medially, but does not extend quite to the 
 primitive segments. Thus a solid plate of cells still remains between the ccelom 
 and the segments the intermediate cell mass (Fig. 81). The ccelom shows no 
 segmentation. (Compare Fig. 80 with Fig. 74 and Fig. Si with Fig. 72.) 
 
 The formation of the neural groove and tube from the ectoderm and the 
 separation of the chorda from the entoderm are processes quite analogous to the 
 development of those same structures in the lower forms. 
 
 As in the chick, so also in Mammals, the blastoderm is at first spread out flat, 
 forming the roof, so to speak, of the yolk sac. At a later period, in connection 
 with the closure of the gut and the establishment of the external forms of the 
 body, the blastoderm assumes a tubular shape (see p. 136). 
 
 A comparison of the foregoing description of the formation of the mesoderm 
 in Mammals with the description of the corresponding processes in the chick 
 (p. 75) shows their essential similarity. 
 
 Strand of mesoderm 
 in exocoelom 
 
 Entoderm 
 of yolk sac 
 
 Mesoderm 
 of yolk sac 
 
 w&ii 
 
 W 
 
 ' 'W W 
 
 ^* 
 
 Part of exocrelom 
 
 Trophoderm 
 
 Mesoderm of chorion 
 Ectoderm of amnion 
 Entoderm 
 Amniotic cavity 
 Embryonic ectoderm 
 Mesoderm 
 Yolk cavity 
 
 Mesoderm 
 
 FIG. 82. Section through human chorion, amnion, embryonic disk, and yolk sac. Peters. 
 
 Compare with Fig. 83. ' 
 
 The Germ Layers in Man. 
 
 Of the actual formation of the germ layers in man, practically nothing is 
 known. There are no observations on the segmentation of the ovum, the first 
 differentiation of cells, or the origin of the embryonic disk and germ layers. 
 A very young human ovum, described by Leopold, does not show any structures 
 which can be interpreted as the embryonic disk or any part of it. Another 
 
86 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 young ovum described by Peters shows all three germ layers and the flat embry- 
 onic disk. Bryce and Teacher have recently described an ovum, the youngest 
 on record, in which all three germ layers are formed (see Fig. 106; cf. Fig. 83). 
 A section through the ovum described by Peters (Fig. 82) shows the ectoderm 
 as a flat layer of stratified or pseudostratified cells, the margin of which is re- 
 flected dorsally as the lining of thereof of the amniotic cavity (compare Fig. 52, c). 
 Beneath the ectoderm is a layer of cells the mesoderm which is continu- 
 
 Coagulum 
 
 Trophoderm 
 | 
 
 Uterine epithelium 
 
 :? ft /jaVflK 
 
 ^f)|Kv^:-5 
 
 . ! -.-:'V.V S ,?;' .-/^O Yolk sac 
 
 ^'^A.^xV^A- 
 
 -* * *****. *J* 1. 1? - f / 
 
 Gland 
 
 Decidua basalis 
 
 Blood 
 
 FlG. 83. Section through very young human chorionic vesicle embedded in the 
 
 uterine mucosa. Peters. 
 
 The vesicle measured 2.4 x 1.8 mm., the embryo .19 mm. Peters reckoned the age as 3 or 4 days, 
 but later studies of other embryos go to show that the age is much greater; Bryce and 
 Teacher estimate it at 14 to 15 days. 
 
 ous at its margin with the mesoderm of the roof of the amnion, with mesoderm 
 lining the chorionic vesicle, and also with the mesoderm covering the yolk sac 
 Fig. 83). Beneath the mesoderm of the embryonic disk is a layer of entoderm 
 which also extends ventrally to line the yolk sac. There is here no trace of an 
 invaginated entoderm from which the mesoderm might arise. 
 
 Graf Spee has described an ovum somewhat older than Peters', in which the 
 embryonic disk shows certain features which are comparable with those in 
 lower Mammals. On surface view (Fig. 84), the primitive groove is especially 
 
GERM LAYERS. 
 
 87 
 
 prominent and the opening at its anterior end, corresponding to Hensen's node, 
 is usually well marked. The line of the head process is strongly marked by a 
 deep groove the neural groove (compare Fig. 84 with Fig. 54, a). 
 
 A longitudinal section in the medial line of this disk (Fig. 85) shows a re- 
 markable similarity to a corresponding section of the bat's disk (Fig. 55). The 
 ectoderm consists of a single layer of columnar cells interrupted only at the 
 opening of the blastopore (anterior end of the primitive groove). The entoderm 
 (chorda anlage) also consists of a single layer of cells which is continuous at the 
 blastopore with the ectoderm. In the region of the primitive groove the per- 
 
 Yolk sac 
 
 A nun on 
 
 Neural groove 
 
 Chorion 
 
 FIG. 84. Dorsal view of human embryo, two millimeters in length, with yolk sac. 
 
 von Spee, Kollmann. 
 The amnion is opened dorsally. 
 
 istomal mesoderm is present. The embryonic disk forms the roof, so to speak, 
 of the yolk sac. 
 
 A transverse section (Fig. 86) through the primitive groove shows all three 
 germ layers fused in the medial line, but separated laterally. In this case there 
 is a striking resemblance to the condition seen in a corresponding section of the 
 rabbit's disk (Fig. 87). 
 
 Apart from the embryonic disk, the conditions are very similar to those in 
 Peters' ovum (compare Figs. 85 and 82). 
 
 The unusual feature in both these embrvos is the enormous extent of the 
 
88 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 mesoderm. In Graf Spec's ovum both longitudinal and transverse sections 
 would suggest the same origin for the intraembryonic mesoderm as in lower 
 
 Chorionic villi 
 
 Mesoderm 
 of yolk sac 
 
 Blood vessel 
 
 FIG. 85. Medial section of human embryo shown in Fig. 84. von Spee, Kottmann. 
 
 Mammals, but the extent of the extraembryonic mesoderm, at this early stage 
 of the embryonic disk, would indicate a departure from the conditions seen in 
 the lower Mammals. In other words, it scarcely seems possible that the 
 
 Ecto- 
 Mesoderm derm Primitive groove 
 
 ^*\ a ^ .jj',3 -^f^p <n < siis ft vt* 
 
 Ectode 
 
 Parietal mesoderm 
 Visceral mesoderm 
 
 Entoderm 
 FIG. 86. Transverse section through primitive streak of embryo shown in Fig. 84. von Spee. 
 
 mesoderm which lines the chorionic vesicle and covers the yolk sac has grown 
 out from the mesoderm which arises within the embryonic disk; it seems more 
 
GERM LAYERS. 
 
 Parietal mesodenn Primitive groove 
 
 Visceral mesoderm I Primitive fold 
 
 Entoderm 
 FIG. 87. Transverse section through primitive groove of rabbit embryo, -van Beneden, 
 
 D 
 
 FIG. 88. Diagrams representing hypothetical stages in the development of the human embryo. 
 
 A, Morula; compare with Fig. 33, a. B, Morula with differentiated superficial cells; compare with 
 Fig- 33, b. C, Central cells have become vacuolized to form the yolk cavity, leaving a small 
 group (the inner cell mass) attached to the enveloping layer (trophoderm) ; compare with 
 Fig. 33, d. D, Cells of the inner cell mass which are adjacent to the yolk cavity have become 
 differentiated and have begun to grow around the cavity, forming the entoderm; compare 
 with Fig. 52, a. 
 
90 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 reasonable to suppose that it has arisen outside the embryonic disk and united 
 with the intraembryonic mesoderm secondarily. 
 
 While neither the origin of the extraembryonic mesoderm, nor its behavior 
 up to the stage in Bryce and Teacher's ovum, has been observed in man, it is 
 possible to construct hypothetical diagrams which allow of comparison with 
 what actually occurs in the lower Mammals. The morula, the differentiation 
 
 - /{trj rji(ftic Ca.vit 
 
 V< see rat __ 
 Mesoderrrj 
 
 Parietal_ 
 Mesoder 
 
 FIG. 89. Diagrams representing hypothetical stages in the development of the 
 
 human embryo (to follow Fig. 88). 
 
 A, Entoderm surrounds the yolk cavity; part of the cells of the inner cell mass have become 
 vacuolated, thus forming the amniotic cavity, while the remainder constitute the embryonic 
 ectoderm; compare with Fig. 52. B, Mesoderm (represented by dotted portion) has appeared 
 between the entoderm and trophoderm, between the entoderm and ectoderm of the embryonic 
 disk, and in the roof of the amnion. C, The mesoderm around the yolk cavity has split into 
 a parietal and a visceral layer, the cleft between being the anlage of the extraembryonic 
 body cavity (exoccelom). 
 
 of the superficial layer of cells, the formation of the trophoderm and inner cell 
 mass, and the differentiation of the primary entoderm may be represented 
 hypothetically by the diagrams in Fig. 88. These are quite comparable with 
 the corresponding stages of development in the bat (Fig. 33). In Fig. 89, A, 
 the amniotic cavity formed by a vacuolization of a part of the inner cell mass is 
 shown, and also the entoderm lining the entire yolk cavity. This is also com- 
 
GERM LAYERS. 
 
 91 
 
 parable with conditions in the bat (Fig. 52). In the next stage (Fig. 89, B) 
 the mesoderm is present all the way around between the trophoderm and ento- 
 derm, in the roof of the amniotic cavity, and between the ectoderm and entoderm 
 in the embryonic disk. It is possible that the mesoderm arises in situ as a deriv- 
 ative of the entoderm or trophoderm. Since in the lower Mammals it arises 
 from entoderm, a similar origin here seems the more reasonable. 
 
 FIG. 90. Diagrams representing stages of development of the human embryo (to follow Fig. 89). 
 A t A stage that corresponds approximately to those of Peters' and Bryce-Teacher's embryos (Figs. 
 83 and 107). Owing to the rapid enlargement of the chorionic vesicle, the exfraembryonic 
 body cavity has become much larger than in Fig. 89, C. B, A stage (in longitudinal section) 
 corresponding to that of von Spec's embryo (Fig. 85). Only a part of the chorion is shown; 
 the embryonic disk is slightly constricted from the yolk sac; note the belly stalk, comparing 
 with A. C, Transverse section, same stage as B. D, Longitudinal section, stage somewhat 
 later than B. Note the greater degree of constriction between the embryo and yolk sac, and 
 the larger amnion. 
 
 In the majority of the lower Mammals the intraembryonic mesoderm arises 
 from the entoderm and then grows out into the wall of the blastodermic vesicle. 
 In a few, however (sheep, roe, shrew), the peripheral mesoderm (p. 83) 
 arises outside of the embryonic disk and unites with the intraembryonic meso- 
 derm secondarily. It might be suggested that the formation of peripheral 
 
92 TEXT-BOOK OF EMBRYOLOGY. 
 
 mesoderm outside of the embryonic disk is an intermediate step between the 
 formation of mesoderm entirely within the embryonic disk and its formation 
 around the entire vesicle, as in the hypothetical case. 
 
 Neither in Peters' nor in Graf Spec's ovum is any embryonic body cavity 
 present. But in both cases a very large cavity exists between the mesoderm of 
 the yolk sac and that of the chorion. This cavity the extraembryonic body 
 cavity (exocodom) probably arises by a splitting of the extraembryonic meso- 
 derm into two layers, parietal and visceral, just as the embryonic body cavity in 
 other Mammals is the result of a splitting of the intraembryonic mesoderm 
 (p. 83). The splitting would occur as shown in Fig. 89, C. The parietal 
 layer which with the trophoderm becomes the chorion, then grows rapidly and 
 becomes widely separated from the visceral layer, the latter with the entoderm 
 constituting the wall of the yolk sac. Thus a stage is reached which is shown in 
 Fig. 89, C, and which corresponds with Peters' ovum (Fig. 83). The embry- 
 onic disk with its yolk sac and amniotic cavity occupies but a small space within 
 the chorionic vesicle. Consult also Fig. 106, showing the Bryce-Teacher ovum. 
 
 The stage corresponding to Graf Spec's ovum would be produced by a fur- 
 ther splitting of the mesoderm in the roof of the amnion, so that finally the em- 
 bryonic disk and yolk sac remain attached to the chorion only by a band of 
 mesoderm, the belly stalk (Fig. 90; compare with Fig. 85). 
 
 Even at this stage, no body cavity is present within the embryonic disk 
 (Fig. 86). When it does appear, however, it becomes continuous laterally with 
 the exoccelom (see Chap. XIV), and the parietal and visceral layers of meso- 
 derm within the embryonic body are continuous, respectively, with the parietal 
 and visceral extraembryonic mesoderm. 
 
 References for Further Study. 
 
 ASSHETON, R.: The Reinvestigation into the Early Stages of the Development of the 
 Rabbit. Quart. Jour, of Mic. Sci., Vol. XXXVII, 1894. 
 
 ASSHETON, R.: The Segmentation of the Ovum of the Sheep, with Observations on the 
 Hypothesis of a Hypoblastic Origin for the Trophoblast. Quart. Jour, of Mic. Sci., Vol. 
 XLI, 1898. 
 
 VAN BENEDEN, E.: Recherches sur les premiers stades du developpement du Murin 
 (Vespertilio murinus). Anat. Am., Bd. XVI, 1899. 
 
 BONNET, R.: Lehrbuch der Entwicklungsgeschichte. Berlin, 1907. 
 
 BONNET, R.: Beitrage zur Embryologie der Wiederkauer gewonnen aus Schafei. Arch. 
 /. Anat. u. Physiol., Anat. Abth., 1884, 1889. 
 
 BONNET, R.: Beitrage zur Embryologie des Hundes. Anat. Hefte, Bd. IX, 1897; Bd. 
 XVI, 1901. 
 
 BRYCE, T. H.,and TEACHER, J. H.: Early Development and Imbedding of the Human 
 Ovum. Glasgow, 1908. 
 
 HARPER, E. H.: The Fertilization and Early Development of the Pigeon's Egg. Am. 
 Jour, of Anat., Vol. Ill, 1904. 
 
 HARTMAN, C. G.: Studies in the Development of the Opossum. Jour, of Morph., Vol. 
 XXVII, 1916. 
 
GERM LAYERS. 93 
 
 HATSCHEK, B.: Studien iiber Entwicklung des Amphioxus. Arbeiten aus dem zool. 
 Instil, zu Wien, Bd. IV, 1881. 
 
 HEAPE, W.: The Development of the Mole (Talpa europaea). Quart. Jour, ofMic. Sci., 
 Vol. XXIII, 1883. 
 
 HERTWIG, O.: Die Lehre von den Keimblattern. In Hertwig's Handbuch der vergleich. 
 u. experiment. Entwickehingslehre der IVirbeltiere, Bd. I, Teil I, 1903. 
 
 HUBER, G. CARL: The Development of the Albino Rat. Memoirs of the Wistar Insti- 
 tute, Xo. 5, 1915. 
 
 HUBRECHT, A. A. W.: Studies on Mammalian Embryology. II: The Development of 
 the Germinal Layers of Sorex vulgaris. Quart. Jour, of Mic. Sci., Vol. XXXI, 1890. 
 
 LILLIE, F. R.: The Development of the Chick. New York, 1908. 
 
 McMuRRiCH, J. P.: The Development of the Human Body. Philadelphia, 1907. 
 
 MINOT, C. S.: Laboratory Text -book of Embryology. Philadelphia, 1903. 
 
 MORGAN, T. H.: The Development of the Frog's Egg. New York, 1897. 
 
 MORGAN, T. H., and HAZEN, A. P.: The Gastrulation of Amphioxus. Jour, of Morphol. t 
 Vol. XYL 1900. 
 
 PATTERSON, J. T.: On Gastrulation and the Origin of the Primitive Streak in the 
 Pigeon's Egg. Biolog. Bull., Vol. XIII, 1907. 
 
 PEEBLES, F.: The Location of the Chick Embryo upon the Blastoderm. Jour, of Ex- 
 periment. Zool., Vol. I, 1904. 
 
 PETERS, H.: Ueber die Einbettung des menschlichen Eies und das fruheste bisher be- 
 kannte menschliche Placentationstadium. Leipzig u. Wien, 1899. 
 
 YON SPEE, GRAP: Beobachtungen an einer menschlichen Keimscheibe mit offener Medul- 
 larrinne und Canalis neurentericus, Arch. f. Anat. u. Physiol., Anal. Abth., 1889. 
 
 SOBOTTA, J.: Die Entwickelung des Eies der Maus vom Schluss der Furchungsperiode 
 bis zum Auftreten der Amnionfalte. Arch. f. mik. Anat., Bd. LXI, 1902. 
 
 WILSON, E. B.: Amphioxus and the Mosaic Theory of Development. Jour, of Morphol., 
 Vol. VIII, 1893. 
 
CHAPTER VII. 
 FCETAL MEMBRANES. 
 
 In all Vertebrates, with the exception of Fishes and Amphibians which lay 
 their eggs in water, there begin to develop at a very early stage certain accessory 
 or extraembryonic structures which may be conveniently called fatal mem- 
 branes. The development of these structures is very closely related to the de- 
 velopment of the embryo itself, and their presence is apparently largely depend- 
 ent upon the very considerable length of embryonic life in these forms, during 
 which it is necessary for the embryo to maintain a definite relation to its food 
 supply and to possess means of discharging waste products. The fcetal mem- 
 branes, therefore, have to do with the protection and nutrition of the growing 
 embryo and also are connected with the care of the w r aste products of fcetal 
 metabolism. 
 
 Under the head of fcetal membranes are to be considered (i) the amnion, 
 (2) the allantois, (3) the chorion; also in connection with these, the yolk sac and 
 the umbilical cord. 
 
 The development of these structures in Mammals and especially in man is 
 extremely complex and can be best understood by comparison with their simpler 
 development in Reptiles and Birds. 
 
 FCETAL MEMBRANES IN BIRDS AND REPTILES. 
 
 Throughout these two classes there is such uniformity in the formation of 
 the fcetal membranes that the chick may be taken as typical. The chief 
 characteristic of these classes, as influencing the form and structure of the fcetal 
 membranes, is the very large amount of yolk stored up within the egg for the 
 nutrition of the embryo. This is made necessary by the early separation of the 
 egg from the mother, in contrast to the close nutritional relationship between 
 mother and foetus which obtains in Mammals (excepting Monotremes) , where 
 the young are retained within the body of the mother up to a comparatively late 
 developmental stage. 
 
 The Amnion. Returning to that point in the development of the blastoderm 
 of the chick where no trace of amnion has as yet appeared, we recall that the 
 blastoderm at this stage consists of three layers, ectoderm, mesoderm and 
 entoderm; that the medial line of the embryo is marked by the neural groove, 
 flanked by the neural folds which are continuous with each other anteriorly; that 
 
 95 
 
96 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 on each side of the neural groove between ectoderm and entoderm the mesoderm 
 is a solid mass of cells, while more laterally the mesoderm is split, its peripheral 
 layer with the adjacent ectoderm forming the somatopleure, its central layer 
 with the adjacent entoderm forming the splanchnopleure; that between soma- 
 topleure and splanchnopleure is the body cavity. Ventral to the neural groove 
 is the notochord, while ventral to the latter is the primitive gut, the roof of which 
 is formed of entoderm (Fig. 72). 
 
 The first indication of amnion formation is the appearance of a fold the 
 head amniotic fold just in front of the anterior union of the neural folds (Figs. 
 
 ar. op. 1 
 ed. mes. 
 h. am. f. 
 
 pr. seg. 
 
 ar. op. 2 
 
 ar. pel. 
 
 FIG. 91. Dorsal view of embryo of bird (Phaeton rubricauda) with fifteen pairs of 
 
 primitive segments. Schauinsland. 
 
 ar. op. 1 , Area opaca, portion in which mesoderm is not yet present; ar. op. 2 , area opaca; ar. pel., 
 area pellucida; cce., bladder-like dilatation of ccelom; ed. mes., edge of mesoderm; h. am. }., 
 head amniotic fold; pr. seg., primitive segments; x, portion of amniotic fold containing no 
 mesoderm. 
 
 91 and 97, b). This occurs during the second day of incubation After the head 
 fold has become well developed and extends back over the embryo like a hood 
 (Fig. 93), similar lateral and tail folds make their appearance (Figs. 92 and 97, 
 a and b). The folds continue to grow over the dorsum of the embryo and 
 finally meet and fuse in the mid-dorsal line, forming the amniotic suture (Fig. 94). 
 The amniotic folds from the beginning involve the somatopleure, that is, 
 the ectoderm and parietal mesoderm. But since they arise some distance from 
 the developing embryonic body, the extraembryonic portions only are involved. 
 At the same time a portion of the extraembryonic body cavity is also carried 
 dorsally within the folds (Figs. 92 and 95). When the folds unite over the 
 
FCETAL MEMBRANES. 
 
 97 
 
 embryo they break through at the line of contact, thus leaving the outer layers 
 of the folds continuous and the inner layers continuous, with the extraembryonic 
 body cavity continuous between the outer and inner layers. 
 
 n. tu. 
 
 t. am. f. 
 
 ect. 
 
 pr. g. 
 
 ent. 
 
 1 ! i i i i 
 
 mes. b.c. al. a.m. e.g. ta. 
 
 FIG. 92. Medial section of caudal end of chick embryo (at end of second 
 
 day of incubation). Duval. 
 
 a/., Beginning of allantoic evagination; a.m., anal membrane; b.c., extraembryonic body cavity; 
 e.g., caudal gut; ect., ectoderm; ent., entoderm; mes., mesoderm; mes. 1 , parietal mesoderm; 
 mes. 2 , visceral mesoderm; n. tu. y neural tube; pr. g., primitive gut; t. am. /., tail amniotic 
 fold; ta., tail. 
 
 The result of the development of the amniotic folds is : 
 i. That the embryo is completely enclosed dorsally and laterally by a cavity, 
 the amniotic cavity, which is lined by ectoderm continuous with the ectoderm- 
 
 Area 
 
 opaca 
 
 Edge of 
 mesoderm 
 
 Dorsal amniotic 
 suture 
 
 Primitive 
 streak 
 
 FIG. 93. Dorsal view of embryo of albatross, showing amnion covering cephalic 
 
 end of embryo. Schaninsland. 
 x, Portion of blastoderm containing no mesoderm. 
 
 later epidermis of the embryo, the ectoderm lining the cavity and the overlying 
 parietal mesoderm together constituting the amnion (Fig. 96). 
 
 2. That the outer parts of the amniotic folds become completely separated 
 
TEXT-BOOK OF EMBRYOLOGY. 
 
 from the inner the amnion to form a second membrane consisting externally 
 of ectoderm, internally of mesoderm and called at first the serosa or jalse 
 amnion, later the primitive chorion (Fig. 96). 
 
 3. That the extraembryonic body cavity unites across the medial line 
 dorsally, thus separating the amnion from the primitive chorion (Fig. 97, a, b 
 and c). 
 
 During the formation of the amnion the chick embryo is becoming more and 
 more definitely constricted off from the underlying large yolk mass which is 
 liquefying and into which the embryo sinks somewhat. At the same time the 
 
 Ant. vitelline vein Mesoderm 
 
 Omphalomesenteric 
 (vitelline) vein 
 
 Primitive streak 
 
 Area opaca 
 Sinus terminalis 
 
 Extraembryonic body cavity 
 
 Amnion 
 Amniotic suture 
 
 Area pellucida 
 
 Amniotic suture 
 ^Lateral amniotic fold 
 
 Tail amniotic fold 
 Area opaca 
 
 FIG. 94. Dorsal view of embryo of albatross, showing amnion covering greater 
 part of embryo. Schauinsland. 
 
 amniotic cavity continues to increase in size and extends also ventrally beneath 
 the embryo so that the embryo is everywhere enclosed within the amnion 
 except at its narrow connection with the yolk (Fig. 97, c, d). 
 
 The amniotic cavity is filled with fluid, the liquor amnii, the origin of which 
 is uncertain. In it the embryo floats freely, attached only by its ventral con- 
 nection with the yolk. At about the fifth day of incubation rhythmical con- 
 tractions of the amnion begin. These are apparently due to the development 
 of contractile fibers in its mesodermic tissue and give to the embryo a regular 
 oscillating motion. 
 
FCETAL MEMBRANES. 
 
 99 
 
 The Yolk Sac. The simplest type of yolk sac is found in Amphibians and 
 Fishes. In Amphibians the yolk is enclosed within the embryo, the cells form- 
 
 p. mes. 
 
 ent. 
 
 pc. ep, 
 
 FIG. 95. Transverse section of embryo of albatross. Schauinsland. 
 
 Section taken through region of heart, am., amnion; ao., aorta; a. v.v., anterior vitelline veins; 
 ect., ectoderm; ent., entoderm; ep., epicardium; ex. b. c., extraembryonic body cavity; ht., heart; 
 /. am./., lateral amniotic fold; pc., pericardium; ph., pharynx; p. mes., parietal mesoderm; 
 ser.. serosa (chorion); v. mes., visceral mesoderm; * point at which extraembryonic body 
 cavity passes over into the intraembryonic (or ccelom proper). 
 
 ing a part of the intestinal wall. The superficial cells are split off to form the 
 yolk entoderm. Investing the yolk entoderm is the visceral mesoderm which 
 
 am. sut. 
 
 ect. 
 
 p. mes. 
 
 v. mes. 
 
 it 
 
 p. pc. 
 
 ht. ph. p. pc. 
 
 FIG. 96. Transverse section of embryo of albatross. Schauinsland. 
 
 Section taken through region of heart, am., Amnion; am. sut., amniotic suture; a. v.v., anterior 
 vitelline veins; ect., ectoderm; ent., entoderm; ex. b. c., extraembryonic body cavity; ht., heart; 
 p. pc., primitive pericardial cavity; ph., pharynx; p. mes., parietal mesoderm; ser., serosa 
 (chorion); v. mes., visceral mesoderm; * point at which extraembryonic body cavity passes 
 over into intraembryonic (or ccelom). 
 
 is separated from the parietal mesoderm by the body cavity. Outside of the 
 parietal mesoderm is the ectoderm (Fig. 65). In many of the Fishes the germ 
 
100 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 disk, as in Reptiles and Birds, is confined to one pole of the egg. Thus in these 
 forms the embryonic body develops on the surface of the large yolk mass. As 
 the embryo develops the germ layers simply grow around the yolk and suspend 
 it from the ventral side of the embryo. At the same time a constriction appears 
 between the embryo and the yolk mass, thus forming the yolk stalk. In this 
 case the yolk is surrounded from within outward, by entoderm, visceral and 
 
 h. am. f. 
 
 y.s. 
 
 z. g 
 
 FIG. 97. Diagrams representing stages in the development of the foetal membranes 
 
 in the chick. Hertiing. 
 
 i, Transverse section; b, c, d, longitudinal sections; yolk represented by vertical lines, al., Allantois; 
 aw., amnion; am. c., amniotic cavity; cce., ccelom; dh., vitel line area between two dotted lines 
 which represent the edge of the mesoderm (at s. t.) and entoderm (at z..); dg., yolk stalk; 
 ds., yolk sac; d. umb., dermal umbilicus; ect., ectoderm; ent., entoderm; ex. b. c., extraem- 
 bryonic body cavity; gh., area vasculosa; h.am.f., head amniotic fold; m., mouth; p.mes., 
 parietal mesoderm; s. /., sinus terminalis; ser., serosa (chorion); t.am.f., tail amniotic fold; 
 umb., umbilicus; r mes., visceral mesoderm; z. g., dotted line represents edge of entoderm. 
 
 parietal mesoderm, and ectoderm (Fig. 98). The yolk furnishes nutriment for 
 the embryo. This is conveyed to the tissues by means of blood vessels. 
 Branches of the vitelline artery ramify in the wall of the yolk sac (in the meso- 
 dermal tissue) ; the branches converge to form the vitelline veins which carry the 
 blood back to the embryo. 
 
 In the chick, while the amnion is forming, the inner germ layer gradually 
 extends farther and farther around the yolk (Fig. 97, a, b, c and d). At the 
 
FCETAL MEMBRANES. 101 
 
 same time, as already noted (p. 98), the growth of the amnion ventrally results 
 in a sharp constriction which separates the embryo from the underlying yolk. 
 This constriction is emphasized by constant lengthwise growth of the embryo. 
 Following the gradual growth of the entoderm around the yolk, the mesoderm 
 also gradually extends around, at the same time splitting into visceral and 
 parietal layers, so that the entoderm is closely invested by visceral mesoderm 
 (Fig. 97, a, b, c and d). Finally, both entoderm and mesoderm enclose com- 
 pletely the mass of yolk. The yolk thus becomes enclosed hi the yolk sac 
 which consists of two layers, entoderm and visceral mesoderm. The constricted 
 connection between the yolk sac and the embryo is the yolk stalk. It is seen by 
 reference to the diagrams (Fig. 97) that the entoderm lining the yolk sac is 
 
 FIG. 98. Diagrammatic longitudinal section of selachian embryo. Hertwig. 
 
 a., Anus; d., yolk sac; dn., intestinal umbilicus; ds., visceral layer of yolk sac; hs., parietal layer of 
 yolk sac; hn., dermal umbilicus; 2k 1 , coelom; lh 2 , exoccelom; m., mouth; St., yolk stalk. 
 
 directly continuous through the yolk stalk with the entoderm lining the primi- 
 tive gut. The transition line between extra- and intraembryonic entoderm is 
 sometimes referred to as the intestinal umbilicus, in contradistinction to the line 
 of union, on the outside of the yolk stalk, of amniotic and embryonic ecto- 
 derm (the latter becoming later the epidermis) which is known as the dermal 
 umbilicus. 
 
 As in Fishes and Amphibians, so also in Reptiles and Birds, the yolk furnishes 
 nourishment for the growing embryo, and is conveyed to the embryo by 
 the blood. At a very early stage the mesoderm layer of the yolk sac (visceral 
 mesoderm) becomes extremely vascular. This vascular area is indicated by an 
 irregularly reticulated appearance in the periphery of the blastoderm and is 
 known as the area vasculosa (Fig. 74). The area vasculosa increases in size as 
 the mesoderm grows around the yolk and its vessels become continuous with 
 those in the embryo (Fig. 212). Some of these vessels enlarge as branches of 
 two large vessels which are given off from the primitive aortae, the mtelline or 
 omphalomesenteric arteries. (When the two aortas fuse to form a single 
 vessel, the proximal ends of the vitelline arteries fuse likewise.) The branches 
 of the arteries ramify in the mesoderm over the surface of the yolk and then 
 
102 TEXT-BOOK OF EMBRYOLOGY. 
 
 converge to form other vessels which enter the embryo as thevitellineoromphalo- 
 mesenteric veins (Fig. 213). As the mesoderm extends farther and farther 
 around the yolk, the vessels extend likewise until the entire yolk is surrounded 
 by a dense plexus of blood vessels in the wall of the yolk sac. 
 
 The Allantois. While the embryonic intestine is first assuming the form 
 of a tube, there grows out ventrally from near its caudal end, during the third 
 day of incubation, a diverticulum which is the beginning of the allantois (Fig. 
 99). This increases rapidly in size and pushes out into the extraembryonic 
 body cavity behind the yolk stalk. As it is a diverticulum from the intestine, 
 it consists primarily of entoderm. This pushes in front of it, however, the 
 splanchnic (visceral) mesoderm which becomes the outer layer of the membrane. 
 The connection between the intestine and the allantois is known as the urachus. 
 In the chick the allantois attains a comparatively large size, pushing out dorsally 
 
 ex.b.c. -' 
 
 al. p. / 
 
 al. mes. ent. a.m. e.g. a.m. 
 
 FIG. 99. Longitudinal section of caudal end of chick embryo (end of third 
 
 day of incubation). Casser. 
 
 al., Allantois; al. p., allantois prominence; a.m., anal membrane; am., amnion; am. c., amniotic 
 cavity; e.g., caudal gut; cce., ccelom; ect., ectoderm; ent., entoderm; ex. b. c., extraembryonic 
 body cavity; mes., mesoderm; pr. g., primitive gut; t., tail. 
 
 between the amnion and the primitive chorion and ventrally between the latter 
 and the yolk sac (Fig. 97, b, c and d). The inner wall of the allantoic sac blends 
 with the amnion about the seventh day of incubation and with the yolk sac con- 
 siderably later, while the outer wall joins the primitive chorion to form the true 
 chorion, or as it is sometimes designated, the allanto-chorion (see p. 107). As 
 the allantois reaches the limit of the yolk, it leaves the latter, and pushing the 
 primitive chorion before it, continues around close under the shell (Fig. 97) 
 until it completely encloses the albumen at the small end of the egg. 
 The allantois of the chick performs three important functions : 
 
 1. It serves as a receptacle for the excretions of the primitive kidneys. 
 
 2. United with a part of the primitive chorion to form the albumen sac, its 
 vessels take up the albumen as nourishment for the embryo. Because of this 
 function and also because of the fact that little papillae sometimes appear on the 
 
FCETAL MEMBRANES. 103 
 
 inner surface of the albumen sac, evidently for the purpose of increasing its 
 absorptive surface, this albumen sac has been compared by some to a placenta. 
 
 3. It blends with the primitive chorion to form the true chorion and being 
 extremely vascular and lying just beneath the porous shell, it serves as the most 
 important organ of fcetal respiration. 
 
 The allantois in the chick is an extremely vascular organ, the network of 
 small vessels in the wall being composed of radicals of the allantoic or umbilical 
 vessels of the embryo. Soon after the allantois begins to develop, two 
 branches the umbilical arteries are given off from the aorta near its caudal 
 end. These pass ventrally through the body wall of the embryo and thence 
 out via the umbilicus to break up into extensive networks of capillaries in the 
 mesodermal layer of the allantois. The capillaries converge to form the um- 
 bilical veins which pass into the embryo via the umbilicus and thence cephalad 
 to the heart. 
 
 During the incubation period of the chick there are two extraembryonic sets 
 of blood vessels. One set, the vitelline (omphalomesenteric) vessels (p. 218), 
 is concerned with carrying the yolk materials to the growing embryo. The 
 other set, the umbilical (allantoic) vessels, is chiefly concerned with respiration 
 and carrying waste products to the allantois, but is probably in part concerned 
 with conveying the albumen to the embryo. When the chick is hatched, and the 
 foetal membranes are of no further use and disappear, the extraembryonic por- 
 tions of the blood vessels also disappear. The intraembryonic portions persist, 
 in part, as certain vessels in the adult organism. 
 
 The Chorion or Serosa. This membrane is but little developed in the 
 chick as compared with Mammals, especially the Placentalia. Its mode of 
 origin as the outer leaves of the amniotic folds, cut off from the amnion by 
 dorso-medial extension of the mesoderm and body cavity, has been described 
 (P- 9?)- It consists, as there shown, of extraembryonic ectoderm and parietal 
 mesoderm (Fig. 96) . As first formed it is confined to the immediate region of 
 the embryo and of the amnion to which it is later loosely attached. It soon 
 extends ventrally around the yolk where it forms what is sometimes designated 
 the skin layer of the yolk sac. The relation of the outer layers of the allantois 
 to the chorion has been described on page 102, and is illustrated in Fig. 99. 
 
 FCETAL MEMBRANES IN MAMMALS. 
 
 The development of the fcetal membranes in Mammals presents no such 
 uniformity as is found in Birds and Reptiles where it was possible to describe 
 their formation in the chick as typical for the two classes. In the different 
 Mammals much variation occurs, not only in the first appearance of the mem- 
 branes but also in their further development and ultimate structure. 
 
 In some forms (rabbit, for example) the amnion develops in a manner very 
 
104 TEXT-BOOK OF EMBRYOLOGY. 
 
 similar to that in the chick; that is, by a dorsal folding of the somatopleure. 
 There is, however, no head fold unless a temporary structure known as the 
 proamnion be considered as such. The entire rabbit amnion is formed by an 
 extension over the embryo of the tail amniotic fold. In other forms (bat and 
 probably man) the amnion and amniotic cavity arise in situ over the embryonic 
 disk, without any folding of the somatopleure. 
 
 Yolk is almost entirely lacking in most Mammals, but the yolk sac is always 
 present although it soon becomes a rudimentary structure. The fact that the 
 yolk sac is always present points toward the conclusion that Mammals are 
 descended from animals which possessed large ova with abundant yolk. As a 
 matter of fact the lowest Mammals, the Monotremes, possess large ova with 
 large quantities of yolk. These are deposited by the female, are developed in a 
 parchment-like shell, and are carried about in the brood-pouch. 
 
 The allantoic sac in many Mammals is a very rudimentary structure which, 
 as in the chick, always arises as an evagination from the caudal end of the gut. 
 The allantoic blood vessels, however, become vastly important since they here 
 not only carry off waste products from the embryo, as in Reptiles and in Birds, 
 but also assume the function of conveying nutriment from the mother to the 
 embryo. In assuming this new function they are no longer concerned with 
 the allantoic sac proper but enter into a new relation with the chorion. 
 
 The chorion is the most highly modified and specialized of all the mam- 
 malian foetal membranes. In some cases (the rabbit, for example) it arises in 
 connection with the amnion, as in the chick, by a dorsal folding of the somato- 
 pleure. In other cases (bat and probably man) it arises at a very early stage, 
 partly as a differentiation of the superficial layer of the rnorula, partly as 
 extraembryonic parietal mesoderm which develops later. In all cases where 
 the embryo is retained in the uterus (except Marsupials) it forms a most highly 
 specialized and complex structure which, in connection with the allantoic 
 vessels, establishes the communication between the mother and the embryo. 
 
 For the sake of clearness it seems best to describe first the earlier stages of 
 the foetal membranes in some case where the development resembles that of the 
 chick; then later to consider the more specialized types of development, the 
 ultimate structure of the membranes, especially the chorion, and their relation 
 to the embryo and the mother. 
 
 Amnion, Chorion, Yolk Sac, Allantois, Umbilical Cord. Referring 
 back to the mammalian blastoderm when it consists of the three germ layers, 
 it will be remembered that the embryonic disk forms the roof, so to speak, of a 
 large cavity the yolk cavity or cavity of the blastodermic vesicle (Fig. 82) ; 
 that the ectoderm of the disk is continuous with a layer of cells which extends 
 around the vesicle the extraembryonic ectoderm; that the entoderm of the 
 disk is continuous with the entoderm lining the cavity of the vesicle; that the 
 
FCETAL MEMBRANES. 
 
 105 
 
 mesoderm extends peripherally beyond the disk between the ectoderm and 
 entoderm (Fig. 89) . It will be remembered also that the mesoderm later splits 
 into two layers the parietal and visceral, of which the parietal plus the ecto- 
 derm forms the somatopleure and the visceral plus the entoderm forms the 
 
 FIG. ioo. Diagrams representing six stages in the development of the foetal membranes 
 
 in a mammal. Modified from Kblliker. 
 
 The ectoderm is indicated by solid black lines; the entoderm by broken lines; the mesoderm 
 
 by dotted lines and areas. 
 
 splanchnopleure; and that the cleft between the two layers is the body cavity 
 or coelom. 
 
 In further development, along with the differentiation of the embryonic 
 body, the somatopleure begins to fold dorsally at a short distance from the 
 
106 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 body (Fig. 100, 2). The folds amniotic folds appear cranially, laterally and 
 caudally. These folds continue to grow dorsally (Fig. 100, 3) and finally meet 
 and fuse above the embryo (Fig. 100, 4). They then break through along the 
 line of fusion so that the extraembryonic body cavity which has been carried up 
 dorsally over the embryo in the amniotic folds becomes continuous across the 
 mid-dorsal line. A double membrane or rather two membranes are thus 
 formed which extend over the embryo. The outer membrane is the chorion 
 and is composed from without inward of ectoderm and parietal mesoderm. 
 The inner membrane is the amnion and is composed from without inward of 
 parietal mesoderm and ectoderm (Fig. 100, 5). Between the amnion and the 
 chorion is a portion of the extraembryonic body cavity, which, as already 
 mentioned, was carried dorsally with the amniotic folds (Fig. 100, 2, 3, 4 and 5). 
 
 Sclefotome Myotome 
 
 Entode 
 
 Pronephric 
 tubule 
 
 FIG. 101. Transverse section of a dog embryo with 19 primitive segments. Bonnet. 
 Section taken through sixth segment. 
 
 In the manner just described the amnion becomes a sac which at first en- 
 closes the embryo laterally, and then laterally and dorsally (Fig. 101). Later 
 as the embryo becomes constricted off from the underlying cavity, the amnion 
 encloses it entirely except over a small area on the ventral side where the embryo 
 is attached to the yolk sac (Fig. 100, 3, 4 and 5). 
 
 While the amnion is being formed, the mesoderm continues to extend 
 around the vesicle between the ectoderm and the entoderm. At the same time 
 it splits into parietal and visceral layers, of which the parietal is applied to the 
 ectoderm, and the visceral to the entoderm. In this way the extraembryonic 
 body cavity gradually extends farther and farther around the vesicle until 
 finally the somatopleure is completely separated from the splanchnopleure 
 (Fig. 100, 3, 4 and 5). The extraembryonic somatopleure now forms a com- 
 plete wall for the vesicle and constitutes the chorion. The extraembryonic 
 splanchnopleure forms a complete wall for the yolk cavity and constitutes the 
 wall of the yolk sac. The proximal portion of the yolk sac becomes constricted 
 
FCETAL MEMBRANES. 107 
 
 to form the yolk stalk which connects the yolk sac with the ventral side of the 
 embryonic body (Fig. 100, 5). 
 
 While the processes just described have been taking place, an evagination ap- 
 pears pushing out from the ventral side of the caudal end of the gut (Fig. 100, 4). 
 This evagination grows out into the extraembryonic body cavity (exo- 
 coelom), pushing before it the visceral layer of mesoderm, thus giving rise to a 
 thin-walled sac which communicates w r ith the gut the allantois (Fig. 100, 5). 
 At this stage the embryonic body, with its surrounding amnion and appended 
 yolk sac and allantois, lies within the large vesicle formed by the chorion. Up 
 to this point the development resembles that in the chick. 
 
 In succeeding stages a new connection is established between the embryo and 
 the chorion in the following manner : The amnion enlarges and fills relatively 
 more of the cavity within the chorion, while the yolk sac becomes smaller and 
 the yolk stalk much attenuated (Fig. 100, 6). At the same time the allantois 
 also becomes attenuated and its distal end comes in contact with the chorion 
 (Fig. 100, 6). The growth of the amnion results in the pushing together of the 
 attenuated yolk stalk and allantois so that they lie parallel to each other (Fig. 
 100, 6), and are together invested by a portion of the amnion. As already 
 described, both yolk stalk and allantois are composed of entoderm and 
 mesoderm while the amnion is composed of mesoderm and ectoderm. Con- 
 sequently when the three structures come together and fuse, there is formed 
 a mass of mesoderm which contains the entoderm of the yolk stalk or vitelline 
 duct and the entoderm of the allantois or allantoic duct, and which is sur- 
 rounded by the ectoderm of the amnion. The fusion of these three structures 
 in this region thus produces a slender cord of tissue which forms the union 
 between the embryo and the chorion and which is known as the umbilical cord 
 (Fig. 100, 6). 
 
 In Mammals the yolk sac contains little or no yolk and consequently can 
 furnish but little nutriment for the embryo; but the union of the allantois with 
 the chorion, mentioned in the preceding paragraph, allows the allantoic blood 
 vessels to come into connection with the chorion. And since in Mammals the 
 chorion is the means of establishing the communication between the embryo 
 and the mother, the allantoic (umbilical) vessels assume the function of carrying 
 nutrient materials to the embryo and also of carrying away from the embryo its 
 waste products. (See p. 223.) 
 
 Further Development of the Chorion. 
 
 Up through the stages which have been described the correspondence in the 
 development of the foetal membranes in Reptiles, Birds and Mammals is clear. 
 From now on, the course of development in Mammals becomes more and 
 more divergent. The extensive development of the yolk and yolk sac with its 
 
108 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 vascular system in the egg-laying Amniotes has been noted. This is dependent 
 upon the fact that the embryo very early in its existence loses its nutritional con- 
 nection with its mother and is therefore dependent for its food upon the yolk 
 stored up within the egg. This condition obtains up through the lowest order 
 of Mammals, the Monotremes, which are egg-laying animals. The Marsupials 
 give birth to young of very immature development. In these two orders of 
 Mammals the foetal membranes present essentially the same condition as in 
 Birds and Reptiles. The chorion in Marsupials, however, lies in close ap- 
 position to the vascular uterine mucosa and perhaps provides for the passage of 
 
 Chorion 
 
 Muscularis 
 
 FIG. 102. Vertical section through wall of uterus and chorion of a pig. Photograph. 
 
 Note especially the close apposition of the chorionic and uterine epithelium (and compare with 
 
 Fig. 103); note also the enlarged blood vessels in the uterine mucosa. 
 
 nutrition from the mother to the embryo. In all higher Mammals, however, no 
 eggs are laid and the embryo early acquires an intimate nutritional relation to 
 its mother. This relation is maintained until the embryo has reached a com- 
 paratively advanced stage of development. As would be expected therefore, 
 there take place, coincidently with the change in nutritional relation between 
 mother and embryo, and dependent upon this changed relation, the already 
 noted decrease in, or entire loss of, yolk and at the same time the development of 
 a special organ of relation between embryo and uterus. This organ is devel- 
 oped mainly from the chorion which becomes highly specialized as compared 
 with the very simple chorion described in the chick. 
 
FCETAL MEMBRANES. 
 
 109 
 
 In some Mammals (e.g., pig, horse, hippopotamus, camel) there develops a 
 more intimate relation between the chorion and the uterine mucosa. In the 
 pig, for example, the chorionic vesicle becomes somewhat spindle-shaped, and, 
 except at its tapering ends, its surface is closely applied to the surface of the 
 uterine mucosa. On that portion of the chorion which is in contact with the 
 uterine mucosa small elevations or projections develop and fit into correspond- 
 ing depressions in the mucosa. These projections involve the epithelial 
 layer (ectoderm) of the chorion and the adjacent connective tissue (mesoderm) 
 (Fig. 102) . Furthermore, the chorionic epithelial cells and the uterine epithelial 
 
 Blood vessel in 
 uterine mucosa 
 
 FIG. 103. From section through wall of uterus and chorion of a pig, showing close relationship 
 between the epithelium of the uterus and that of the chorion. Photograph. 
 
 cells acquire very intimate relations in that the ends of the former become 
 rounded and fit into depressions in the ends of the latter (Fig. 103). 
 
 The allantois and allantoic vessels in the pig afford a good example of the 
 transition from the respiratory and excretory functions which they almost ex- 
 clusively possess in Reptiles and Birds, to the additional nutritional function of 
 these vessels in Mammals. The allantoic sac becomes large and applies itself 
 to the inner surface of the chorion, so that the blood vessels of the allantois also 
 grow into and ramify in the mesodermal layer of the chorion. This brings the 
 allantoic (umbilical) blood vessels containing the foetal blood closer to the uterine 
 vessels containing the maternal blood. The two sets of vessels never come in 
 contact, however, being always separated by the chorionic and uterine epithe- 
 
110 TEXT-BOOK OF EMBRYOLOGY. 
 
 Hum and also by some connective tissue of the chorion and of the uterine 
 mucosa (Fig. 103). Food materials for the embryo must, therefore, pass through 
 the connective tissue and the two epithelial layers in order to get from the 
 maternal to the fcetal blood; and waste products from the embryo must also pass 
 through the same tissues to get from the fcetal to the maternal blood. When the 
 fcetal membranes of the pig are expelled at birth, the rudimentary chorionic 
 villi simply withdraw from their sockets in the uterine mucosa and the chorion 
 is cast off, leaving the uterine mucosa intact. 
 
 In other Mammals, the attachment of the chorion to the mucous membrane 
 of the uterus is restricted to certain definite, highly specialized areas. This 
 means that the villi which at first developed over the entire chorion, disappear 
 from the -greater part of. it. Those villi which remain are limited to a definite 
 area or areas and develop extensive arborizations. /. Moreover, they do not 
 
 FIG. 104. Chorion of sheep, showing cotyledonary placenta. O. SchuHze. 
 
 simply fit into depressions in the uterine mucosa, but become much more 
 closely attached to it while the mucosa increases in thickness and in vascularity 
 over the villous areas. There are thus formed two distinct though intimately 
 associated parts of a structure which is known as the placenta the uterine part 
 being designated the maternal placenta or placenta uterina, the fcetal part the 
 placenta j&talis. Such Mammals are grouped as Placentalia. In the sheep 
 and cow a number of placentae multiple placentce are normally present (Fig. 
 104). In the dog and cat the placenta takes the shape of a band or a zone 
 of specialized tissue encircling the germ vesicle. This is known as a zonular 
 placenta. In man a single discoidal area develops discoidal placenta. 
 
 These different forms of placentae vary also in regard to the intimacy with 
 which maternal and fcetal parts are associated. Thus, for example, in the 
 multiple placentae of the cow and sheep, the fcetal placentae may be easily 
 
FCETAL MEMBRANES. Ill 
 
 pulled away from the maternal placentae; while in the discoidal placenta of 
 man, maternal and fcetal parts are so closely related that both come away to- 
 gether as the after-birth or decidua. 
 
 THE FCETAL MEMBRANES IN MAN. 
 
 The fcetal membranes in man are characterized by the early development of 
 the amnion, the development of an extremely complicated discoidal placenta and 
 the rudimentary condition of the yolk sac and'allantois. The high develop- 
 ment of the placenta the organ of interchange between foetal and maternal 
 circulation is undoubtedly dependent upon the very long period of gestation 
 during which the human foetus leads an entirely parasitic existence, being 
 dependent wholly upon the mother for nutrition and respiration. The exten- 
 sive development of the placenta in turn explains the rudimentary condition of 
 the yolk sac and stalk and of the allantois, the nutritional and respiratory func- 
 tions of these large and important organs in some of the lower animals, being hi 
 man taken up by the placenta. 
 
 The Amnion. 
 
 In describing the development of the germ layers in the human embryo, 
 comparisons were made between one of the youngest known human embryos 
 that of Peters and the embryos of the bat and mole (p. 87). Reference to this 
 description and to the figures shows that in the bat and mole the amnion is 
 formed, not as in the chick and rabbit by dorsal foldings of the somatopleure 
 and fusion of these folds, but in situ by a breaking down of some of the cells of 
 the inner cell mass and consequent cavity formation. In Peters' embryo the 
 amnion is already present as a closed cavity. The earlier stages in its forma- 
 tion are not known. As in the case of the germ layers, however, the appear- 
 ances in sections are so closely similar as to suggest at least, that the human 
 amnion is formed in the same manner as that of the bat and mole. 
 
 In Peters' ovum (Fig. 83), also in Bryce-Teacher's (Fig. 106), the 
 amniotic cavity is seen already formed. It is roofed by a single layer 
 of flat cells apparently analogous to the trophoderm of the bat (Fig. 52). 
 As in the bat and chick this layer is continuous with the higher ecto- 
 derm of the embryo proper as represented here by the embryonic disk. The 
 extraembryonic mesoderm is already present at this stage between the ecto- 
 derm of the amnion and the trophoderm, the epithelial cells of the latter 
 being seen on the surface. Ventrally lies the yolk sac lined with entoderm, 
 while laterally between the entoderm and ectoderm is seen the embryonic 
 mesoderm. This formation of the amnion in situ considerably shortens the 
 process of amnion formation as compared with that in most of the lower 
 animals, where it is formed by dorsal foldings. This results in the very early 
 
112 TEXT-BOOK OF EMBRYOLOGY. 
 
 formation of a complete amnion and amniotic cavity in such forms as the bat, 
 mole and man. 
 
 The human amniotic cavity is at first small, the amnion covering only the 
 dorsum of the embryo to which it is closely applied. The dorsal surface of the 
 disk is at first concave, then flat, and later its margins curve ventrally as the flat 
 disk becomes transformed into the definite shape of the embryonic body. As 
 the margins of the disk bend ventrally they carry with them the attached amnion. 
 As the embryo becomes constricted off from the yolk sac, the amnion is attached 
 only ventrally in the region of the developing umbilical cord. With the 
 exception of this attachment the embryo thus comes to lie free, floating in 
 the amniotic fluid (Fig. 100, 6). 
 
 The amniotic cavity, at first small, increases rapidly in size and by the third 
 month has reached the limits of the chorionic vesicle completely filling it. It 
 then attaches itself loosely to the overlying chorion thus completely obliterating 
 the extraembryonic body cavity. The amnion consists everywhere of two 
 layers, an outer ectoderm, the cells of which are at first flat, later cuboidal or 
 even columnar, and an inner layer of somatic mesoderm. At the dermal navel 
 (p. 101) the amniotic ectoderm is continuous with the surface ectoderm (later 
 epidermis) of the embryo. Some writers consider the fact that the epithelial 
 covering of the umbilical cord is stratified as indicating that it is derived from 
 embryonic ectoderm rather than from amniotic ectoderm, and describe the 
 transition between the two as taking place not at the dermal umbilicus but at 
 the attachment of the cord to the placenta. As in lower forms (p. 98) the 
 walls of the amniotic cavity contain contractile elements which determine 
 rhythmical contractions of the amnion. 
 
 The human amniotic fluid is a thin, watery fluid of slightly alkaline reaction 
 containing about one per cent, of solids, chiefly urea, albumin and grape- 
 sugar. The origin of the fluid is not known. By some it is believed to be 
 mainly a secretion of the maternal tissues, by others as largely of fcetal origin. 
 The urea it contains is probably excreted by the fcetal kidneys. 
 
 When the amount of amniotic fluid is excessive the condition is known as 
 hydramnios. If, as is sometimes the case, the amniotic fluid is present in very 
 small amount, adhesions may form between the amnion and the embryo. 
 These may result in malformations. With or without abnormality in the 
 amount of amniotic fluid, bands of fibrous tissue may stretch across the cavity. 
 If sufficiently strong these may produce such malformations as splitting of 
 a lip or of the nose, or the partial or complete amputation of a limb. 
 
 In labor a portion of the amnion filled with fluid usually precedes the head 
 through the cervical canal. It is rounded or conical, and becoming distended 
 and tense with each uterine contraction or labor pain, serves as the natural 
 and most efficient dilator of the cervix. When the cervix is partially or com- 
 
FCETAL MEMBRANES. 113 
 
 pletely dilated, the amnion usually ruptures " rupture of the membranes" 
 and all or a part of the amniotic fluid escapes as the "waters." Usually a 
 varying amount of the fluid remains behind the embryo being kept there by the 
 head completely corking the cervix. This escapes with the birth of the child. 
 In some cases the amnion ruptures at the beginning of labor, before there has 
 been any dilatation of the cervix. The dilating must then be done by the 
 child's head or other presenting part. These are much less adapted to the 
 purpose than the bag of membranes and the result is usually a difficult and 
 protracted "dry " labor. Rarely the amnion fails to rupture during labor and 
 the child is born within the intact bag of membranes. Such a child is said to 
 be born with a "caul." 
 
 The Yolk Sac. 
 
 In the human embryo the yolk sac is but a rudiment of the large and im- 
 portant organ found in some of the lower animals. It develops early and at the 
 end of the second week is an almost spherical sac with a wide opening into the 
 intestine (Fig. 121), there being but a slight constriction between the embryo 
 and the yolk sac. During the third week the yolk sac becomes decidedly con- 
 stricted off from the embryo, remaining connected, however, with the intestine 
 by means of a long pedicle, the yolk stalk or vitelline duct (Fig. 123). As the 
 placenta is formed, and at the same time the umbilical cord, the yolk sac becomes 
 incorporated with the former, where it may sometimes be found by careful 
 search after birth, w r hile the yolk stalk becomes reduced to a strand of cells 
 which traverses the entire length of the umbilical cord (p. 130). 
 
 Whatever function the rudimentary human yolk sac has, must be performed 
 early, as both sac and stalk soon undergo regressive changes. Although no true 
 yolk is present, the sac at first contains fluid and its thick outer mesodermal layer 
 is the place of earliest blood and blood vessel formation. This would seem to 
 indicate that like the larger yolk sac of lower animals, the human yolk sac 
 serves temporarily as a blood-forming organ. 
 
 In about three per cent, of cases that portion of the yolk stalk which lies 
 between the intestine and the umbilicus fails to degenerate, retaining its lumen 
 and its connection with the intestine. It is then known as MeckeVs diverticulum 
 and is of considerable surgical importance, as it may become invaginated into 
 the small intestine and thus cause obstruction of the bowel. The blind end of 
 the diverticulum may remain attached to the umbilicus, or it may become free, 
 or in rare cases the stalk may retain a lumen from the intestine to the umbilicus, 
 through which faeces may escape "faecal fistula." Occasionally a portion of 
 the gut from which the yolk stalk is given off extends for a short distance into 
 the cord. If, as is sometimes the case, this extension fails to retract before 
 birth, a congenital umbilical hernia is the result (see Chap. XIX). 
 
114 TEXT-BOOK OF EMBRYOLOGY. 
 
 The Allantois. 
 
 The human allantois, while analogous to the allantois of Birds and Reptiles, 
 shows certain marked peculiarities in its development, in its relation to sur- 
 rounding structures and in its functions. 
 
 Its development is peculiar in that it does not push out, as, for example, in 
 the chick, as an evagination from the primitive gut into the extraembryonic 
 body cavity, for at the very early stage at which the human allantois first ap- 
 pears, the primitive gut is not as yet constricted off from the yolk sac and there 
 is no extraembryonic body cavity into which the allantois can extend. It will be 
 remembered that in the formation of the germ layers and in the development of 
 the amnion the human embryo shows a marked tendency, as compared with 
 lower forms, toward a shortening of the developmental process. This ab- 
 breviation and consequent very early formation applies also to the allantois. As 
 the embryonic body assumes definite shape and the amnion is formed, there is 
 not the complete separation of amnion from the chorion seen, for example, in the 
 chick, the embryo remaining connected posteriorly with the chorion by means of 
 a short thick cord of mesodermic tissue. This is known as the belly stalk. Into 
 this solid cord of mesodermic tissue which connects the embryo with the 
 chorion, entodermic cells extend. These are derived from the embryonic en- 
 toderm before the constriction which differentiates the primitive gut from the 
 yolk sac has made its appearance (Fig. 85). According to some there is a true 
 evagination from the entodermic sac quite analogous to the evagination in the 
 chick, resulting in a long slender tube lined by entoderm and extending from 
 the embryo to the chorion. Others describe the entodermic outgrowth as a 
 solid cord of cells. The mesodermic layer of the allantois is furnished by the 
 mesoderm of the belly stalk. It is to be noted in this connection that the 
 mesoderm of the belly stalk is embryonic mesoderm and that in Birds, for 
 example, this portion of the mesoderm splits into two layers, somatic and 
 splanchnic, with the extraembryonic body cavity between them. Into this 
 extraembryonic body cavity the allantois extends. In man no such splitting 
 occurs, so that there is no extraembryonic body cavity into which the allantois 
 can extend. Instead, it grows out into the belly stalk. 
 
 The functions of the human allantois are somewhat different from those of 
 the allantois of the chick. In the latter it is a direct respiratory organ in that it 
 brings the embryo into relation with the outside air. In man the allantois, 
 accompanied by the allantoic (umbilical) blood vessels, comes into relation 
 with the placenta. As the placenta serves as the medium of exchange between 
 fcetal and maternal circulations, it acts as a modified organ of respiration. In 
 the chick the allantoic cavity also serves for the reception of the excretions from 
 the embryo, the allantoic fluid containing nitrogenous excretives. In man all 
 
FCETAL MEMBRANES. 115 
 
 such elimination is carried on through the placenta and there is consequently 
 no need for the development of a large allantoic sac. 
 
 With development of the placenta, that part of the allantoic stalk which lies 
 in the umbilical cord atrophies. Of the embryonic portion of the allantois, 
 or the urachus, on the other hand, the proximal end communicates with the 
 urinary bladder, while the remainder, which extends from the bladder to the 
 umbilicus becomes transformed into a fibrous cord, the middle umbilical 
 ligament (page 401). Rarely that portion of the allantoic stalk between the 
 bladder and the umbilicus remains patent and opening upon the surface 
 forms a "urinary fistula," allowing urine to escape. 
 
 In Reptiles and Birds the omphalomesenteric vessels, passing along the yolk 
 stalk and ramifying in the mesodermal layer of the yolk sac, convey the nutrient 
 materials of the yolk to the growing embryo. Since the allantois is an organ of 
 respiration and excretion, the allantoic or umbilical vessels have nothing to do 
 with the actual nourishment of the embryo (p. 222). In Mammals the yolk sac 
 is of less functional value. Consequently the vitelline vessels, although present 
 (Fig. 215), play a less important role in conveying nutriment. The allantoic 
 (umbilical) vessels, instead of ramifying in the wall of the allantois, as in the 
 lower forms, come into connection with the chorion, passing primarily through 
 the belly stalk. Since the chorion becomes the organ of interchange between 
 the embryo and the mother, the allantoic vessels assume a new function, the 
 allantoic (umbilical) vein carrying food material from the mother to the em- 
 bryo, the arteries carrying waste products from the embryo to the mother. 
 Thus in Mammals, as the yolk sac and vitelline vessels come to play a less im- 
 portant role in the nutrition of the embryo, the allantoic vessels, in connection 
 with the chorion, become practically the only means by which the embryo 
 receives its food-supply. 
 
 The Chorion and the Decidua. 
 
 When the fertilized ovum reaches the uterus it becomes fixed or embedded 
 in the uterine mucosa. Fixation usually occurs in the upper half of the uterus 
 but may occur near the cervix. Rarely the ovum becomes fixed to the mucous 
 membrane of the tube instead of to that of the uterus, and, developing there, 
 gives rise to a "tubal" pregnancy one of the forms of extrauterine gestation. 
 
 Until recently, it was believed that the ovum became attached to the surface 
 of the mucous membrane. Recent studies upon some of the youngest human 
 ova and upon those of some of the lower Mammals, however, seem to indicate 
 that the ovum in some w r ay pushes itself into buries itself in the uterine 
 mucosa (Fig. 105). It is argued that if the ovum simply attaches itself to the 
 surface of the mucosa, one would expect to find, for a time at least, epithelium 
 between the attached surface and the stroma. In a very young human ovum 
 
116 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 no such epithelium was found and the ovum had the appearance of having 
 penetrated the stroma by which it was surrounded (Fig. 106). Thus, for the 
 first two weeks of gestation, the ovum lies embedded in the stroma of the uterine 
 mucosa, giving so little surface indication of its presence that it is practically 
 impossible to locate it except by serial sections of the entire mucosa. After 
 two weeks the position of the ovum begins to be indicated by a slight prominence 
 of the mucous membrane, the summit of the prominence being marked by an 
 entrance plug consisting of coagulum, cast off cells and fibrin (Fig. 83). In 
 
 Uterine 
 epithelium 
 
 Thickening of 
 trophoderm 
 
 Uterine 
 epithelium 
 
 Thickening of L 
 
 trophoderm 
 
 Degenerating 
 
 uterine epithelium 
 
 FIG. 105. Successive stages in the implantation of the ovum of Spermophilus citillus. Rejsek. 
 
 a. Ovum (blastodermic vesicle) lying free in the uterine cavity, b, Later stage in which the 
 
 syncytial knob (thickening of trophoderm) has penetrated the uterine epithelium as far as 
 
 the basement membrane, c, Still later stage in which the trophoderm has penetrated the 
 
 uterine stroma; the cells of the uterine epithelium at the point of entrance are degenerating. 
 
 the Bryce-Teacher ovum no such entrance plug was found (Fig. 106). At 
 this stage the plug contains no glands or blood vessels. Later it becomes 
 organized and replaced by connective tissue. Whatever the mode of fixation 
 of the ovum to the uterus, there immediately result important changes in the 
 uterine mucosa which lead to the formation of the decidua. These changes are 
 both destructive and constructive. They are destructive in that the epithelial 
 covering of the ovum, the trophoderm, has some solvent action on the uterine 
 mucosa and breaks down the walls of the maternal blood vessels thus allowing 
 the blood to flow around the ovum (Fig. 106). They are constructive in that 
 they result in the formation of the decidua. 
 
FCETAL MEMBRANES. 
 
 117 
 
 From their relation to the ovum and to the uterus, the deciduae (by which is 
 meant the uterine mucosa of pregnancy) have been divided into the decidua 
 farietalis or decidua vera the decidua basalis or serotina, and the decidua cap- 
 sularis or reflexa. 
 
 
 rt <n 
 IS 
 
 S 
 O 
 
 S 
 
 Capillary; cy*., cellular layer (cyto-trophoderm) ; e/>., uterine epithelium; gl., uterine gland; 
 11. z., necrotic zone of decidua (uterine mucosa); P.e., point of entrance of the ovum; tro., 
 
 svncvtmm 
 
 (plasmodium, plasmodi-trophoderm); tro. 1 , masses of vacuolating syncytium 
 invading capillaries. The cavity of the blastodermic vesicle is completely filled by mesoderm, 
 
 and embedded therein are the amniotic and entodermic (yolk) vesicles, 
 portions of the several parts have been observed. 
 
 The natural pro- 
 
 The decidua parietalis is the changed mucosa of the entire uterus with the 
 exception of that portion to which the ovum is attached. The decidua basalis 
 is that portion of the mucosa to which the ovum is attached and which later 
 becomes the maternal part of the placenta. The decidua reflexa is either the 
 
118 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 extension of the mucosa over the ovum or that part of the mucosa under which 
 the ovum buries itself (Fig. 107). 
 
 It will be remembered that surrounding the entire young ovum is the chorion 
 and that this membrane consists of two layers, an outer ectoderm (trophoderm) 
 and an inner mesoderm. In the youngest known human embryo the chorion is 
 
 Decidua parietalis 
 Decidua capsularis 
 
 Decidua basalis ] 
 Chorion frondosum I 
 
 Placenta 
 
 FIG. 107. Semidiagramatic sagittal section of human uterus containing an 
 
 embryo of about five weeks. Allen Thompson. 
 
 a, Ventral (anterior) surface; c, cervix uteri; ch, chorian; g, outer limit of decidua; 
 m, muscularis; p, dorsal (posterior) surface. 
 
 a shaggy membrane, its entire surface being covered with small projections or 
 villi. Later these villi disappear from all of the chorion except that part of it 
 which becomes attached to the uterine mucosa and forms the foetal part of the 
 placenta. The latter is known as the chorion frondosum, while the smooth 
 remainder of the chorion is known as the chorion lave. 
 There are thus to be considered: 
 
 1. The decidua parietalis. 
 
 2. The decidua capsularis. 
 
 3. The decidua basalis 
 
 4. The chorion frondosum 
 
 forming the placenta. 
 
FCETAL MEMBRANES. 119 
 
 The Decidua Parietalis. The changes in the uterine mucosa which 
 result in the formation of the decidua parietalis are similar to, though more 
 extensive than, the changes which take place during the earlier stages of men- 
 struation. There is congestion of the stroma with proliferation of the con- 
 nective tissue elements and increase in the length, breadth and tortuosity of the 
 glands. These changes result as in menstruation in thickening of the mucosa 
 so that at the height of its development the decidua parietalis has a thickness of 
 about i cm. It extends to the internal os where it ends abruptly, there being no 
 decidua formed in the cervix. 
 
 In the superficial part of the mucosa the glands wholly or almost wholly 
 disappear and their place is taken by the proliferating connective tissue of the 
 stroma. The result is a layer of comparatively dense connective tissue the 
 compact layer. Beneath this layer are found remains of the uterine glands in 
 the shape of widely open, somewhat tortuous spaces which extend for the most 
 part parallel to the muscularis. Some of these glandular remains retain part 
 of their epithelium. Lying in the proliferating stroma, these spaces give to this 
 layer the structure which has led to its being designated the spongy layer. 
 
 During the latter half of pregnancy the decidua parietalis becomes greatly 
 thinned, due apparently to pressure from the growing embryo with its mem- 
 branes. With this thinning, the few remaining glands of the compact layer 
 disappear. The character of the spongy layer changes, the glands collapsing or 
 being reduced to elongated, narrow spaces parallel to the muscularis. The 
 entire tissue also becomes much less vascular than in early pregnancy. 
 
 If the fcetal membranes are in situ the compact layer is in contact with the 
 ectodermic (epithelial) layer of the chorion. Next to this lies the mesodermic 
 (connective tissue) layer of the chorion. Delicate adhesions connect the 
 mesodermic tissue of the chorion with the mesodermic layer of the amnion. 
 Covering the latter is the amniotic ectoderm (epithelium). 
 
 The Decidua Capsularis. Early in its development this has essentially 
 the same structure as the decidua parietalis. Its older or more common name, 
 decidua reflexa, indicates the earlier idea that this portion of the decidua repre- 
 sents a growing around or reflection of the uterine mucosa upon the attached 
 ovum. Peters, after examining the very early ovum which bears his name, 
 came to the apparently warranted conclusion that instead of the uterine mucosa 
 growing out around the ovum, the ovum buries itself in the mucosa, and that by 
 the time the ovum had reached the size of the one he examined (i mm.), it was 
 almost entirely covered over by the mucosa (Fig. 83). See also Fig. 106. In 
 Peters' ovum a coagulum consisting of blood cells, other cast off cells and 
 fibrin marked the point at which the ovum probably entered the stroma. 
 Later this is replaced by connective tissue and for a considerable time the point 
 is marked by an area of scar tissue. 
 
120 TEXT-BOOK OF EMBRYOLOGY. 
 
 By about the fifth month the rapidly growing embryo with its membranes 
 has filled the uterine cavity, and the decidua capsularis, now a very thin trans- 
 parent membrane, is everywhere pressed against the decidua parietalis. It 
 ultimately either disappears (Minot) or blends with the decidua parietalis 
 (Leopold, Bonnet). 
 
 The Decidua Basalis. As the decidua basalis is that part of the mucosa 
 to which the chorion frondosum is attached, it is convenient to consider the 
 two structures together. 
 
 Decidua 
 
 "Fastening" villi 
 
 Terminal villi 
 
 Vein 
 Chorion 
 
 FIG. 108. Isolated villi from chorion frondosum of a human embryo of 
 eight weeks. Kollmann's Atlas. 
 
 At a very early stage, villi develop over the entire surface of the chorion 
 (Fig. 106). Very soon, however, the villi begin to increase in number and in 
 size over the region of the attachment of the ovum and to disappear from the 
 remainder of the chorion, thus leading to the already mentioned distinction 
 between the chorion frondosum and the chorion laeve (p. 118). 
 
 THE CHORION FRONDOSUM or fcetal portion of the placenta consists of two 
 layers which are not, however, sharply separated. 
 
 1. The compact layer. This lies next to the amnion and consists of con- 
 nective tissue. At first the latter is of the more cellular embryonal type. Later 
 it resembles adult fibrous tissue. 
 
 2. The villous layer. The chorionic villi, when they first appear, are short 
 
FCETAL MEMBRANES. 
 
 121 
 
 simple projections from the epithelial layer of the chorion and consist wholly of 
 epithelium. Very soon, however, two changes take place in these projec- 
 tions. They branch dichotomously giving rise to secondary and tertiary villi, 
 forming tree-like structures (Fig. 108). At the same time mesoderm grows 
 into each villus so that the central part of the originally solid epithelial villus is 
 replaced by connective tissue, which thus forms a core or axis. This connective 
 tissue core is at first free from blood vessels, but toward the end of the third week 
 terminals of the umbilical (allantoic) vessels grow out into the connective tissue 
 and the villus becomes vascular. Each villus now consists of a core of vascular 
 mesodermic tissue (embryonal connective tissue) covered over by trophoderm 
 
 Syncytium 
 
 Cellular layer 
 (of Langhans) 
 
 Blood vessels 
 
 Mesoderm 
 (core of villus) 
 
 Intervillous 
 space 
 
 FIG. 109. Section of proximal end of villus from chorion frondosum of human embryo 
 
 of two months. Photograph. 
 
 In the space above the villus is a mass of cells such as are invariably found among or attached to 
 
 the villi (see text, page 126). 
 
 (epithelium). At first the epithelium of the villus consists of distinctly outlined 
 cells. Very soon, however, the epithelium shows a differentiation into two 
 layers. The inner layer lying next to the mesoderm is called the layer of 
 Langhans or cyto-trophoderm. Its cell boundaries are distinct and its nuclei 
 frequently show mitosis. The outer covering layer consists of cells the bodies 
 of which have fused to form a syncytium the syncytial layer or plasmodi- 
 trophoderm. This is a layer of densely stained protoplasm of uneven thickness 
 (Figs. 109 and no). It contains small nuclei which take a dark stain. As 
 this layer is constantly growing, and as these nuclei do not show mitosis, it has 
 been suggested that they probably multiply by direct division. 
 
122 TEXT-BOOK OF EMBRYOLOGY. 
 
 At an early stage large masses of cells appear among the villi, sometimes being 
 attached to the villi (Figs. 109 and in). The origin of these masses is not known 
 with certainty. They may represent thickenings of the syncytium in which the 
 cell boundaries have reappeared, or they may represent outgrowths from 
 Langhans' layer. In some cases the cells are small with darkly staining nuclei, 
 in other cases large and homogeneous with large vesicular nuclei. Large 
 multinuclear cells, or giant cells, with homogeneous cytoplasm, also appear. 
 In some cases they apparently lie free in the intervillous spaces although 
 
 Hofbauer's cell 
 
 Capillary 
 
 FIG. no. Transverse section of chorion villus from human embryo of two months, showing meso- 
 dermal core of villus and surrounding cellular layer (cyto-trophoderm) and syncytium (plas- 
 modi-trophoderm). Hofbauer's cell is an example of large cells found in the villi, but the 
 significance of which is not known. From retouched photograph. Grosser. 
 
 it is claimed by some investigators that they merely represent sections of 
 tips of the syncytial masses. A structure known as canalized fibrin (which 
 takes a brilliant eosin stain) begins to develop in the earlier months of preg- 
 nancy and gradually increases in amount during the later stages. It is found 
 in relation with the large cell masses among the villi and is probably a degen- 
 eration product of these masses. 
 
 In the later months of pregnancy the covering layer of the villi loses its 
 distinctly epithelial character, the cyto-trophoderm or cellular layer disappearing 
 and the plasmodi-trophoderm or syncytial layer becoming reduced to a thin 
 
FCETAL MEMBRANES. 
 
 123 
 
 homogeneous membrane. At points in this membrane are knob-like projections 
 composed of darkly staining nuclei. These are known as nuclear groups, or 
 proliferation islands, and probably represent the proximal portions of the large 
 cell masses already described (compare Figs, no and 112). 
 
 Certain of the uterine stroma cells increase greatly in size and become the 
 deddual cells. These are large cells 30 to 100 microns and vary in shape. 
 Late in pregnancy they acquire a brownish color and give this color to the 
 superficial layer of the decidua parietalis. Each cell usually contains a single 
 
 "Giant" cell 
 Syncytium 
 
 Canalized 
 fibrin 
 
 Syncytium 
 
 Trophoderm 
 mass 
 
 FIG. in. Section of chorion of human embryo of one month (9 mm.). Grosser. 
 
 large nucleus. Some contain two or three nuclei. A few are frequently 
 multinuclear. 
 
 Some of the chorionic villi float freely in the blood spaces of the maternal 
 placenta floating 'uilli; others are attached to the maternal tissue fastening 
 villi. The villi are separated into larger and smaller groups or lobules by the 
 growth of connective tissue septa from the maternal placenta down into the 
 decidua basalis. These are known as placental septa, while the groups of 
 chorionic villi are known as cotyledons (Figs. 113 and 115). 
 
 Both decidual cells and chorionic villi are important from a diagnostic 
 
124 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 standpoint, as the finding of them in curettings or in a uterine discharge may 
 be accepted as proof of pregnancy. 
 
 During the early months of pregnancy first four months the decidua 
 basalis has essentially the same structure as the decidua parietalis. Its surface 
 epithelium disappears very early, perhaps even before the attachment of the 
 ovum. The glandular elements and the connective tissue undergo the same 
 changes as in the decidua parietalis and here also result in the differentiation 
 of a compact layer and a spongy layer. Both layers are much thinner than 
 in the decidua parietalis. 
 
 As already noted, connective tissue septa pass from the superficial layer of the 
 decidua basalis down into the fcetal placenta subdividing the latter into cotyle- 
 dons. At the margin of the placenta the decidua basalis passes over into the 
 
 Remnant of syncytium 
 Capillaries 
 
 Remnant 
 of syncytium 
 
 y* Capillary 
 
 JSfcS^ai 
 Nuclear group 
 
 FIG. 112. Transverse sections of chorionic villi at the end of pregnancy. Schaper. 
 
 thicker decidua parietalis and here the chorion is firmly attached to the decidua 
 basalis. 
 
 There still remains to be considered what may be called the border zone 
 between the decidua basalis and the chorion frondosum. The whole purpose 
 of the placenta is the interchange of materials between the maternal and fcetal 
 circulation. It is in the border zone that this interchange takes place. The 
 entire structure of this zone is for this function, while all the rest of the placenta 
 serves to transport the blood to and from this area. We have considered on the 
 maternal side the structure of the superficial (compact) layer of the decidua 
 basalis (p. 119), on the fcetal side the structures of the villous layer of the chorion 
 frondosum (p. 120). Unfortunately, this border zone has an extremely com- 
 plicated structure which is difficult of interpretation in the usual microscopic 
 section. This has led to much confusion in description and many differences 
 of opinion as to actual structure. We can here consider only the more generally 
 
FCETAL MEMBRANES. 
 
 125 
 
 accepted facts, referring the student to special articles on the subject for further 
 details. 
 
 In the fully developed placenta, the chorionic villi lie either free (floating 
 
 villi) or attached to the decidua (fastening villi) in what are known as inter- 
 villous spaces (Fig. 113). In sections the villi are, on account of their structure, 
 
126 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 Blood vessel 
 
 Base of villus 
 
 in section 
 
 ^ : -lv ; USi-ii^I:^ \ Uterine glards 
 ^ = j^^_.' ? !?? I r ! r' j Base of decidua 
 
 ,Muscular coat 
 of uterus 
 
 FlG. 114. Vertical section through wall of uterus and placenta in situ; about seven months' 
 
 development. Minot. 
 
FCETAL MEMBRANES. 
 
 127 
 
 cut in all directions, many sections of villi being entirely free from their basal 
 connections. The villi thus present the appearance of projections, peninsulas, 
 or islands lying in spaces filled with blood (Fig. 114). 
 
 Branches from the arteries of the uterine muscularis enter the decidua basa- 
 lis. They take very tortuous courses through the latter and in it lose their con- 
 nective tissue and muscular coats, and, while of considerably larger diameter 
 than most capillaries, become reduced to endothelial tubes. These follow the 
 intervillous (placental) septa in which they branch and from which they finally 
 open directly into the intervillous spaces along the edges of the cotyledons. 
 The maternal blood is thus poured into the intervillous spaces at their peri- 
 phery. After flowing through them it passes into veins which leave the 
 intervillous spaces near the center of the cotyledons (Fig. 113). 
 
 Chorion laeve +.. 
 Decidua parietalis' 
 
 r" Decidua basalis 
 
 Cotyledon 
 (lob'e) 
 
 Cotyledon 
 (lobe) 
 
 FIG. 115. Placenta at birth, seen from the uterine side. Bonnet. 
 
 The relation of these spaces to the maternal blood vessels is not easy to make 
 out in ordinary sections, but many observations have established the fact that 
 both arteries and veins open directly into the spaces. The entire system of 
 intervillous spaces may thus be considered as a part of, or an appendage to, the 
 maternal vascular system, the maternal blood flowing from the arteries into 
 these spaces and returning from these spaces to the mother through the veins. 
 The fcetal blood, on the other hand, circulates in the capillaries of the connective 
 tissue of the villi separated from the maternal blood of the intervillous spaces by 
 the epithelial villous covering already described (p. 121). It is between the 
 maternal blood of the intervillous spaces and the foetal blood in the villous 
 capillaries that the interchange of material takes place. Both the maternal 
 and fcetal vascular systems are clcsed systems so that no blood can pass directly 
 
128 TEXT-BOOK OF EMBRYOLOGY. 
 
 from mother to foetus or from foetus to mother. This can be absolutely proved in 
 early pregnancy by the fact that nucleated red cells are at this stage constantly 
 present in the blood of the foetus but never normally present in the maternal 
 circulation. The normal circulation of blood through spaces unlined by endo- 
 thelium is such a remarkable exception in histology that repeated attempts 
 have been made to demonstrate an endothelial lining to the intervillous spaces 
 but, up to the present time, no such lining has been found. 
 
 The manner in which the intervillous spaces are formed still remains the 
 subject of much controversy. The similarity of development in the human 
 ovum and in the ovum of the bat has already been noted. In the bat the 
 chorion when first formed consists of two thin layers, an inner mesodermal 
 layer and an outer ectodermal layer (trophoderm). From analogy there is 
 every reason to believe that the early human chorion has the same struc- 
 ture. Proof of this is, however, as yet wanting, as in the earliest human ova 
 the trophoderm is already a thick layer. There are also present over the 
 entire surface of the chorion and thus in contact not only with the future 
 decidua basalis but also in contact with the entire future decidua capsularis, 
 well developed villi, each consisting of a core of mesoderm and of a thick covering 
 of trophoderm (Fig. 83). Between the villi, bounded by the villi and by the 
 decidua, are pools of maternal blood. Peters suggested that rapid prolifera- 
 tion of the cells of the trophoderm might result in an opening up of the maternal 
 vessels with which they came in contact and give rise to repeated effusions of 
 maternal blood. This blood would be poured out mainly within the tropho- 
 derm but bounded externally by the decidua. The blood pools thus formed 
 would represent the first stage in the formation of the intervillous spaces. Ac- 
 cording to Bonnet and others the chorionic villi of the developing placenta are 
 constantly opening up new decidual vessels, the trophoderm eroding or dis- 
 solving more and more decidual tissue, so that the intervillous spaces are con- 
 stantly increasing in size with growth of the placenta. 
 
 The placenta at birth is a discoid mass of tissue between 15 and 20 cm. in 
 diameter, about 3 to 4 cm. thick and weighs from 500 to 1200 grms. As its 
 area of attachment marks the point where the ovum becomes fixed to the 
 uterine mucosa and as the point of fixation of the ovum varies, the placenta may 
 be attached to any portion of the uterine wall. It is most frequently attached 
 in the region of the fundus and more frequently to the posterior wall than to 
 the anterior. If the fixation of the ovum is sufficiently low, the placenta may 
 partly or completely close the internal os, thus giving rise to what is known as 
 placenta prcBvia. 
 
 The Umbilical Cord. As the amnion grows and extends ventrally with 
 the ventral bending of the embryonic disk, the yolk stalk and sac, now very 
 much attenuated, become pressed against the cord of mesodermal tissue which 
 
FCETAL MEMBRANES. 129 
 
 connects the embryo with the chorion, and incorporated with it to form the 
 umbilical cord (Figs. 89 and 90). 
 
 The umbilical cord thus consists of: (Fig. 116) : 
 
 1. Amnion. This is attached to the embryo at the navel. It is at first 
 loosely connected with the underlying tissue of the cord so that it is easily 
 peeled off; later it becomes firmly adherent. The epithelium of the amniotic 
 covering of the cord is stratified and is described by some (Minot, McMurrich) 
 as of embryonic ectodermic origin instead of as part of the amnion. 
 
 2. What may be called the ground substance or substantia propria of the 
 cord. This is an embryonic connective tissue often described as "mucous 
 
 Umbilical vein 
 
 Amnion 
 
 Allantoic 
 stalk 
 
 FIG. 116. Transverse section of umbilical cord of a pig embryo six inches in length. Photograph* 
 
 tissue." It consists of a soft gelatinous intercellular substance and irregular, 
 branching stellate cells. On account of its consistency it has been called 
 "\Yharton's jelly." 
 
 3. Three umbilical vessels two arteries and one vein. All these vessels 
 are thick walled and the developing smooth muscle is in bundles separated by 
 considerable connective tissue. The two umbilical arteries carry venous blood 
 from the foetus to the placenta where their branches ultimately give rise to the 
 capillaries of the chorionic villi. From the villi the blood enters the terminals 
 of the umbilical vein and returns as arterial blood to the foetus (Fig. 217). 
 
 As they traverse the cord the arteries make a number of spiral turns around 
 the vein and give to the cord the appearance of being spirally twisted. The 
 
130 TEXT-BOOK OF EMBRYOLOGY. 
 
 cause of this twisting is not known. In places where the turns are quite abrupt 
 and there are considerable accumulations of connective tissue, the cord has a 
 knotted appearance. These points are known as false knots. Rarely the cord 
 is actually tied into a more or less complex knot true knot probably due to 
 movements of the foetus. 
 
 4. Remnants of the allantoic stalk and of the yolk stalk. These, if present, 
 are continuous or broken cords of epithelial cells. Rarely one or the other may 
 retain its lumen or some of the yolk stalk vessels may remain. 
 
 As the yolk stalk is carried around to be incorporated as part of the umbilical 
 cord there is enclosed with it a small part of the extraembryonic body cavity. 
 
 The human umbilical cord averages 50 cm. in length and has a diameter of 
 about 1.5 cm. 
 
 The Expulsion of the Placenta and Membranes. After the birth of the 
 child, the uterine contractions usually cease temporarily and the uterine walls 
 remain contracted around the placenta. In the course of a few moments the 
 uterine contractions are resumed and the placenta and membranes are ex- 
 pelled as the after-birth. 
 
 The line of separation of the placenta and of the decidua parietalis from the 
 uterine mucosa is through the deeper part of the spongy layer (Fig. 113). By 
 this separation many blood vessels are opened, the hemorrhage being con- 
 trolled by the firm contractions of the uterine muscle. The condition of the 
 uterine mucosa, after child-birth, has been described as an exaggeration of its 
 condition at the end of menstruation. Reconstruction of the mucosa takes 
 place by proliferation of the still remaining connective tissue and of the gland- 
 ular elements, 
 
 Anomalies. 
 
 The manner in which the placenta is formed by excessive development of 
 the decidua and chorion over a limited area and atrophy of the chorion through- 
 out the remainder of its extent suggests the most frequent variations from the 
 normal. 
 
 The villi instead of developing over the usual discoidal area may develop along 
 a band-like area which more or less completely encircles the chorion. This gives 
 rise to an annular placenta similar to that seen in the Carnivora. Continued 
 development of the villi over the entire chorion may occur. This results in a 
 thin "placenta membranacea." Such a placenta is apt to be adherent and may 
 thus cause a serious postpartum condition. Failure of the villi to atrophy and 
 their continued development over more than a single area give rise to variations 
 in form and number of placentae. When there are two not very distinctly 
 separated areas the condition is known as placenta bipartita. Two completely 
 separated placentae with distinct branchings of the umbilical vessels to supply 
 
FCETAL MEMBRANES. 131 
 
 them are known as placenta duplex. Placenta triplex and up to placenta septu- 
 plex have been described. When one or more placental lobules develop at a 
 little distance from the main placental mass but connected with the latter by 
 blood vessels, the result is the not uncommon placenta succenturiata. Placenta 
 spuria is applied to such an accessory lobule when it has no vascular connection 
 with the main placenta and consequently no function. 
 
 Anomalies of the placenta associated with multiple pregnancies and with 
 anomalies of the foetus will be found under their respective heads. 
 
 Anomalies of the cord are for the most part dependent upon anomalies of 
 the foetus and of the placenta. 
 
 References for Further Study. 
 
 BEXEKE: Sehr junges menschliches Ei. Monatsschr. f. Geburtshilfe u. Gynakologie, Bd. 
 XXII, 1904. 
 
 BONNET, R.: Lehrbuch der Entwickelungsgeschichte des Menschen. Berlin, 1907. 
 
 BRYCE, T. H.: Embryology. In Quain's Anatomy, nth ed., Vol. I, 1908. 
 
 BRYCE, T. H., and TEACHER, J. H.: An Early Ovum Imbedded in the Decidua. 
 Glasgow, 1908. 
 
 CRAGIX, E. B.: Text-book of ObstetricG. 1915. 
 
 FRASSI, L.: Uber ein junges menschliches Ei in situ. Arch.f. mik. Anat., Bd. LXX, 1907. 
 
 GROSSER, O.: Die Eihaute und der Placenta. 1908. 
 
 HERTWIG, O.: Lehrbuch der Entwickelungsgeschichte des Menschen und der Wirbel- 
 tiere. Berlin, 1906. 
 
 HOFBAUER, J.: Biologic der menschlichen Placenta. Wien and Leipzig, 1905. 
 
 HUBRECHT, A. A. W.: Placentation of Erinaceus Europaeus. Quart, Jour, of Mic. Sci. t 
 Vol. XXX, 1889. 
 
 Vox HUEKELOM, S. I Ueber die menschliche Placentation. Archiv. fur Anat. und Physiol., 
 Anat. Abth., 1898. 
 
 KEFBEL, F., and MALL, F. P.: Manual of Human Embryology. Vol. I, 1910. 
 
 KOLLMAXX, J.: Lehrbuch der Entwickelungsgeschichte des Menschen. Jena, 1898. 
 
 KOLLMAXX, J.: Handatlas der Entwickelungsgeschichte des Menschen. Bd. I, 1907. 
 
 LEOPOLD, G.: Ueber ein sehr junges menschliches Ei in situ. Leipzig, 1906. 
 
 MARCHAXD, F.: Beobachtungen an jungen menschlichen Eiem. Anat. Hejte, Bd. XXL 
 1903. 
 
 McMuRRicH, J. P.: The Development of the Human Body. Philadelphia, 1907. 
 
 MINOT, C. S.: Uterus and Embryo. Jour, of MorphoL, Vol. II, 1889. 
 
 MIXOT, C. S.: Laboratory Text -book of Embryology. Philadelphia, 1903. 
 
 PETERS, H.: Ueber die Einbettung des menschlichen Eies und das friiheste bisher 
 bekannte menschliche Placentationsstadium. Leipzig, 1899. 
 
 MERTTEXS, J.: Beitrage zur normalen und pathologischen Anatomic der menschlichen 
 Placenta. Zeitschr. /. Geburtshilje u. Gynakologie, Bd. XXX, XXXI, 1894. 
 
 REJSEK, J.: Anheftung (Implantation) des Saugetiereies an die Uteruswand, insbesondere 
 des Eies von Spermophilus citillus. Arch. f. mik. Anat., Bd. LXIII, 1904. 
 
 Rossi DORIA, T.: Ueber die Einbettung des menschlichen Eies, studirt an einem kleinen 
 Eie der zweiten Woche. Arch. f. Gynak., Bd. LXXVI, 1905. 
 
 SELEXKA, E.: Studien iiber die Entwickelungsgeschichte der Tiere; (MenschenatTen) . 
 Wiesbaden, 1901-1906. Parts 8-10. 
 
132 TEXT-BOOK OF EMBRYOLOGY. 
 
 STRAHL, H. : Die Embryonalhiillen der Sauger und die Placenta. In Hertwig's Handbuch 
 der vergleich. u. experiment. Entwickelungslehre der Wirbeltiere. Bd. I, Teil II, 1902. 
 WEBSTER, J. C.: Human Placentation. Chicago, 1901. 
 
CHAPTER VIII. 
 THE DEVELOPMENT OF THE EXTERNAL FORM OF THE BODY. 
 
 The segmentation of the ovum and the formation of the blastodermic vesicle 
 have not been observed in man. For these stages it is necessary, therefore, to 
 depend upon the lower Mammals. In those Mammals in which the processes 
 have been observed, the segmentation of the ovum produces a solid mass of 
 cells known as the morula (Fig. 88; compare with Fig. 33). The superficial 
 cells of the morula then become differentiated from those in the interior. The 
 result is a solid sphere composed of a central mass of polyhedral cells and an 
 enveloping layer of somewhat flattened cells (Fig. 88; compare with Fig. 33). 
 The cells of the enveloping layer become still more differentiated from those of 
 the central mass, and the sphere continues to increase in size owing to the pro- 
 liferation of both kinds of cells. The next step in development is the formation 
 of a cavity within the sphere. Among Invertebrates, where but little yolk is 
 present and where no distinct differentiation of the superficial cells occurs, the 
 central cells are displaced, or pushed toward the periphery, so that the morula is 
 changed into a hollow sphere the Uastula the wall of which is composed of a 
 single layer of cells (p. 46). Among Mammals, however, instead of a displace- 
 ment of the central cells, there appear within the cells vacuoles which continue 
 to enlarge and finally become confluent, thus forming a cavity which occupies 
 the greater part of the interior of the sphere. There remain then, after the 
 vacuolization, the enveloping cells, or trophoderm, and a few of the central cells 
 which are attached to the trophoderm over a small area and constitute the 
 inner cell mass (Fig. 88). The latter is the anlage of the embryonic body. 
 As stated on page 48, the cavity of the sphere in Mammals is not homologous 
 with the cavity of the blastula in the lower forms, but the vacuolization of the 
 cells probably represents a belated and abortive attempt at yolk formation. 
 
 Following the formation of the yolk cavity, those cells of the inner cell mass 
 which border it become differentiated, proliferate and gradually spread out in a 
 single layer that finally forms a complete lining for the cavity. The cells of this 
 layer constitute the primitive entoderm (Fig. 88). In the meantime some of the 
 cells of the inner cell mass which lie between the differentiating entoderm and 
 the trophoderm undergo a process of vacuolization, leaving only a single layer 
 closely applied to the entoderm. This layer is the embryonic ectoderm, and the 
 newly formed cavity between it and the trophoderm is the amniotic cavity 
 
 133 
 
134 TEXT-BOOK OF EMBRYOLOGY. 
 
 (Fig. 89; compare with Fig. 52). The further development of the latter has 
 been described on page 112. 
 
 At this stage the sphere contains two cavities, the larger yolk cavity and the 
 smaller amniotic cavity, separated by a double layer of cells, the ectoderm and 
 entoderm, which constitute the embryonic disk. The greater part of the wall of 
 the sphere is composed of two layers; the portion forming the wall of the larger 
 yolk cavity being composed of trophoderm and entoderm, the portion forming 
 the wall of the smaller amniotic cavity being composed of trophoderm alone 
 (Fig. 89). The entire structure is spoken of as the Uastodermic 'vesicle. 
 
 FIG. 117. Human embryo of two months (twenty-six millimeters). Photograph. 
 The embryo lies within the chorion (open on one side), to which it is attached at the right of the 
 figure by the umbilical cord; around the point of attachment the chorionic villi can be seen. 
 The amnion has been opened and turned back. 
 
 The formation of the mesoderm has been discussed elsewhere (Chap. VI, 
 p. 81). At this point it is sufficient to say that it appears in the wall of the 
 yolk cavity as a third layer between the trophoderm and entoderm, and, in the 
 embryonic disk, between the ectoderm and entoderm. Thus the blastodermic 
 vesicle possesses all three germ layers (Fig. 89). 
 
 In the further course of development the mesoderm splits into two layers, 
 an outer or parietal and an inner or visceral. Between the layers a cleft ap- 
 pears, which is completely bounded by mesoderm, on the outer side by the 
 parietal, on the inner side by the visceral. The parietal and visceral layers 
 are in apposition to the trophoderm and entoderm respectively. The two 
 layers of mesoderm soon become widely separated owing to rapid growth of 
 the parietal layer and the trophoderm. The parietal layer of mesoderm and 
 
DEVELOPMENT OF THE EXTERNAL FORM OF THE BODY. 
 
 135 
 
 the trophoderm together constitute the chorion; the original cavity of the 
 blastodermic vesicle with its wall of entoderm and visceral mesoderm is the 
 yolk sac; the newly acquired cavity between the chorion and yolk sac is the 
 extraembryonic body cavity or exocoelom. The embryonic disk lies on one side 
 of, and might be said to form the roof of the yolk cavity. 
 
 A very young human embryo described by Peters (Fig. 83) corresponds ap- 
 proximately to the stage of development shown in Fig. 90, A . The entire 
 
 Amniotic cavity 
 
 Muscular coat 
 of uterus 
 
 Decidua 
 
 parietalis + 
 
 capsularis 
 
 Cervix 
 
 FIG. 118. Opened uterus containing membranes and foetus of three months. Length of 
 foetus, thirty-five millimeters. Natural size. Bonnet. 
 
 vesicle measures about i mm. in diameter and encloses the small, flat em- 
 bryonic disk with its appended yolk sac. The disk proper consists of three 
 layers of cells the ectoderm, mesoderm and entoderm. The chorion is widely 
 separated from the yolk sac by the exoccelom. See also Fig. 106. 
 
 An embryo slightly more advanced than that described by Peters has been 
 described by von Spec (Fig. 84) . In this case a furrow the neural groove 
 appears on the dorsal (ectodermal) side of the embryonic disk, and the latter is 
 
136 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 somewhat elongated in the direction of the furrow. At the sides and ends the 
 disk is bent ventrally so that a depression is formed around it. The margin of 
 the disk is continuous with the amnion and with the yolk sac (Figs. 85 and 90, 
 B, C). The disk as a whole shows a trace of constriction from the yolk sac, 
 but at one end remains attached to the chorion by means of a mesodermal 
 structure the belly stalk (Fig. 85). 
 
 Still a little further advanced than von Spec's embryo, is one described by 
 
 Cerebral plate 
 
 Amnion 
 
 Heart 
 
 Ant. entrance to 
 prim, gut (Ant. 
 Intest. portal) 
 
 Post, entrance to 
 prim, gut (Post, 
 intest. portal) 
 
 \ Yolk sac 
 (cut edge) 
 
 Yolk sac ~ 
 
 Neural tube 
 
 Belly stalk 
 
 Neural fold 
 Neural groove 
 
 Neural fold 
 
 FIG. 119. (a) Ventral view; (b) dorsal view of human embryo with 8 pairs of primitive 
 
 segments (2.11 mm.). Eternod. From models by Ziegler. 
 
 In b the amnion has been removed, merely the cut edge showing; in a the yolk sac has 
 
 been removed. 
 
 Eternod (Fig. 119). What was originally the embryonic disk has here become 
 more elongated, and has assumed a sort of cylindrical shape owing to the rolling 
 under of the lateral margins. As a part of the rolling under process, the depres- 
 sion which originally surrounded the disk has become deeper and has effected a 
 still greater degree of constriction between the cylindrical body and the yolk 
 sac. The caudal end of the body remains attached to the chorion by means of 
 the belly stalk. The lips of the neural groove have turned dorsally and fused in 
 the middorsal line along part of their course. 
 
DEVELOPMENT OF THE EXTERNAL FORM OF THE BODY. 
 
 137 
 
 From a comparison of the three stages which have been mentioned, it can be 
 inferred that the process which establishes the cylindrical form of the body is 
 essentially one of bending of the margins of the embryonic disk with accom- 
 panying elongation of the disk. It is obvious that the process begins at an early 
 period coincident with the appearance of the primitive streak and neural 
 groove. The margins of the disk bend ventrally and form the lateral body walls 
 (Figs. 90, C, and 84), then bend inward and finally meet in the midventral line 
 to form the ventral body wall. At the same time the body gradually be- 
 comes elongated in the direction of the neural groove (Fig. 119). When the 
 body walls bend inward a constriction is produced between the body and the 
 
 Fore-brain 
 
 Neural tube 
 
 Omphalomesenteric 
 vein 
 
 Yolk sac 
 
 Amnion 
 
 fc- Belly stalk 
 
 FIG. 1 20. Dorso-lateral view of human embryo with fourteen pairs of primitive 
 segments (2.5 mm.). Kollmann. 
 
 yolk sac. As the body and yolk sac enlarge, the constriction becomes relatively 
 deeper until the yolk sac is attached to the ventral side of the body by a slender 
 cord the yolk stalk (Fig. 123). While in the earlier stages there is an active 
 bending of the margins of the disk, in the later stages the body grows rapidly in 
 size, especially in length, and extends out beyond the yolk sac (Fig. 120). This 
 makes it appear that the yolk stalk is becoming smaller. As a matter of fact, 
 the diminution in the relative size of the yolk stalk is more apparent than real, 
 the apparent diminution being caused largely by the rapid increase in size of the 
 embryonic body and yolk sac. There is, however, a considerable distance where 
 fusion occurs in the midventral line as the two lateral body walls meet to form 
 
J38 TEXT-BOOK OF EMBRYOLOGY. 
 
 the ventral body wall. This line of fusion is significant in its relation to certain 
 malformations (Chap. XIX). 
 
 Preceding the processes which establish the cylindrical form of the body, 
 there are changes in the relation of the amnion to the chorion. Primarily, the 
 entire dome-like roof of the amniotic cavity is attached to the chorion (Fig. 90, A) . 
 In further development, however, the extraembryonic mesoderm between the 
 trophoderm of the chorion and the ectoderm of the amnion splits farther back 
 over the embryo, leaving the latter attached at its caudal end to the chorion by a 
 mass of mesoderm the so-called belly stalk (Figs. 90, B, and 85). 
 
 Following the above mentioned changes in the amnion, chorion, yolk sac 
 and embryonic disk, the amnion continues to enlarge and thus draws the belly 
 
 Cephalic 
 flexure 
 
 Branchial arches 
 
 Branchial grooves 
 
 Heart 
 
 -^MMB* mi- -3n Yolk sac 
 
 Dorsal flexure 
 
 Amnion -*" 
 
 Belly stalk 
 Chorion 
 
 FIG. 121. Human embryo 2.15 mm. long. His. 
 
 stalk under the embryonic body and brings it closer to the yolk sac. Fir*!iy, as 
 the yolk stalk becomes longer and more slender, the belly stalk and ytrlk stalk 
 unite and become completely surrounded by the amnion. There is thu~, formed 
 a cord-like structure the umbilical cord which is attached to the veiztral side 
 of the body (Figs. 90, D, and 100; see also p. 128). 
 
 The changes which occur in the simple cylindrical body, after it is once 
 formed, consist of the differentiation of the head, neck and body regions and the 
 development of the extremities. Even in Eternod's embryo (Fig. 119) the 
 cephalic end has become proportionately larger than the rest of the body and 
 projects somewhat beyond the yolk sac. This marks the beginning of the 
 
DEVELOPMENT OF THE EXTERNAL FORM OF THE BODY. 139 
 
 head. The extreme end of the head region is bent ventrally almost at a right 
 angle to the long axis of the body, the bend being known as the cephalic flexure. 
 On the ventral side of the body and cranial to the attachment of the yolk sac 
 there is a rather large protrusion which indicates the position of the heart. 
 Between the protrusion and the bent part of the head there is a deep depres- 
 sion the oral fossa. A series of bilaterally symmetrical structures appear in 
 the body region along the sides of the neural tube. These are the primitive 
 segments (mesodermic somites). 
 
 All these features are even more clearly shown in Fig. 120, which represents 
 
 Cephalic 
 flexure 
 
 ^^^^^^^^_ Naso-frontal process 
 
 Maxillary process -fl 
 
 ^B ^ JSf- Oral fossa 
 
 Branchial groove I 
 
 Branchial arch II ~M ^ Mandibular process 
 
 J_ , Ventral aortic trunk 
 
 m^ 
 
 Primitive 
 
 Umbilical vein 
 
 Belly stalk 
 Sacral flexure 
 
 FIG. 122. Human embryo of the third week. His. 
 
 an embryo 2.5 mm. in length. There is also a further increase in the size of 
 the head region. A distinct concavity, caused by the dorsal flexure, is seen in 
 the dorsum of the embryo. 
 
 Another embryo, apparently older but only 2.15 mm. long, shows a re- 
 markable exaggeration of the dorsal flexure (Fig. 121). The middle part of the 
 body seems to be drawn ventrally by the yolk sac. While this may be a 
 normal feature at this stage, it soon disappears and the concavity becomes a 
 convexity (see p. 140). A new feature also appears in this embryo in the form 
 of two vertical depressions just caudal to the head region. These depressions 
 
140 TEXT-BOOK OF EMBRYOLOGY. 
 
 represent the beginning of the branchial grooves and branchial arches, which are 
 exceedingly important in the development of the face and neck regions. The 
 branchial arches and grooves are the morphological equivalents of the gills 
 and gill slits in lower Vertebrates (Fishes, larvae of Amphibians). 
 
 In an embryo somewhat further advanced (Fig. 122) the body as a whole 
 is more robust. The heart is more prominent, and this region is still larger in 
 proportion to the body than in the preceding stages. The dorsal flexure is 
 much reduced. The cephalic flexure is more marked than in the preceding 
 stages. Two other flexures have appeared the cervical flexure just caudal to 
 the head region, the sacral flexure near the caudal end of the body. All these 
 flexures together make the embryo as a whole appear crescentic in form. The 
 primitive segments are at the highest degree of their development and extend 
 from the cervical flexure to the caudal end of the body. 
 
 The two vertical depressions in the head region, which were seen in the 
 preceding stage (Fig. 121), are more prominent here as the first and second 
 branchial grooves or clefts. Just caudal to these two other similar depressions 
 appear as the third and fourth branchial grooves. Cranial to the first groove, 
 between the first and second, between the second and third, and caudal to the 
 third are elevations which mark the first, second, third and fourth branchial 
 arches respectively. A strong process, the maxillary process, has grown 
 cranially from the dorsal part of the first arch. The main part of the arch is 
 the mandibular process. 
 
 In a somewhat later stage (Fig. 123) further distinct changes have occurred, 
 some of which rather than leading toward the adult form of the body are de- 
 partures from it. For example, all the flexures have increased to such an extent 
 that the tail almost touches the head, the entire body being decidedly concave on 
 the ventral side. The dorsal flexure, instead of forming a concavity in the back, 
 now forms a distinct convexity and gives the back a rounded appearance. As a 
 general rule, the tail at this stage is bent to the right, but in some cases the bend 
 is toward the left. 
 
 The branchial arches and grooves are especially prominent. The fourth 
 (and last) arch has appeared and caudal to this, the fourth (and last) groove. 
 The first three arches have enlarged and become elongated so that they almost 
 meet their fellows of the opposite side in the midventral line. The site of 
 the external ear is marked by the second branchial groove. In addition to 
 this, the anlagen of the other sense organs are apparent. The optic vesicle is 
 seen just cranial to the dorsal end of the first arch; the nasal fossa as a distinct 
 depression on the ventral side of the head cranial to the first arch. The yolk 
 sac has become so constricted at its base that it is now readily divisible into 
 the long, slender yolk stalk and the yolk sac or vesicle. 
 
 On the side of the body, just caudal to the cervical flexure, a small protu- 
 
DEVELOPMENT OF THE EXTERNAL FORM OF THE BODY. 
 
 141 
 
 berance forms the anlage of the upper extremity. This is known as the upper 
 limb bud. A similar protuberance caudal to the sacral flexure is the lower limb 
 bud. 
 
 Fig. 124 shows a stage slightly further advanced than Fig. 123. The embryo 
 as a whole is more stocky, and the head is still larger in proportion to the rest 
 of the body. This feature is especially noticeable from this stage up to the 
 time of birth. The sacral and cervical flexures are still very prominent. The 
 
 Cervical Cervical 
 
 depression flexure 
 
 Dorsal flexure 
 
 Branchial arch IV 
 Branchial groove III 
 Branchial arch III 
 Branchial groove II 
 Branchial arch II 
 Branchial groove I 
 Branchial arch I 
 Mandibular process 
 Maxillary process 
 Eye 
 Nasal pit 
 
 Heart 
 Yolk stalk 
 
 Lower limb bud 
 
 Primitive segments 
 
 Upper limb bud Liver Sacral flexure 
 FIG. 123. Human embryo with twenty-seven pairs of primitive segments (7 mm., 26 days). 
 
 Mall. 
 
 dorsal flexure, however, is less prominent and the body of the embryo is more 
 nearly straight. The sacral and cervical flexures from this time on become 
 more and more reduced, while the cephalic flexure, which primarily affects the 
 embryonic brain, persists as the mid-brain flexure in the adult. 
 
 The branchial arches are actually no smaller but appear less prominent. 
 Between the mandibular process and the maxillary process there is a distinct 
 notch which corresponds to the angle of ilw mouth. The second arch has 
 enlarged at the expense of the third and fourth, has grown back over them to a 
 
142 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 certain extent and partially hides them. The nasal fossa is deeper, and ex- 
 tending from it to the optic vesicle is a groove the naso-optic furrow which 
 bounds the maxillary process on the cephalic side. 
 
 The tail (not clearly shown in the figure) is proportionately smaller. It 
 does not actually diminish in size, but the more rapid growth of the body makes 
 it appear to diminish. The limb buds are larger and a transverse constriction 
 divides the upper into a proximal and a distal portion. The corresponding 
 constriction in the lower limb bud has not yet appeared. The protrusion on the 
 
 Branchial groove III 
 
 Branchial arch III 
 
 Branchial groove II 
 
 Branchial arch II 
 
 Branchial groove I 
 
 Mandibular process 
 
 Maxillary process 
 
 Eye 
 
 Naso-optic furrow 
 Nasal pit 
 
 Yolk sac 
 
 Heart 
 
 Lower 
 limb bud 
 
 Liver 
 
 Upper Umbilical 
 limb bud cord 
 
 Yolk stalk 
 
 FIG. 124. Human embryo with 28 pairs of primitive segments (7.5 mm.). Photograph. 
 
 ventral side of the body, originally caused by the heart, is now more prominent 
 owing to the fact that the rapidly growing liver also protrudes ventrally. In this 
 particular case the yolk sac seems unusually large. The yolk stalk has become 
 enclosed for about half its length within the umbilical cord. 
 
 After the stage just described the dorsal flexure becomes still less prominent, 
 the body of the embryo being less curved (Fig. 125). The cervical flexure 
 remains distinct, so that the head is bent at a right angle to the long axis of the 
 body. Two slight depressions have appeared on the dorsum of the embryo 
 the occipital depression just cranial to the cervical flexure, the cervical depression 
 
DEVELOPMENT OF THE EXTERNAL FORM OF THE BODY. 143 
 
 just caudal to the cervical flexure. The cervical depression becomes more con- 
 spicuous in later stages and finally persists as the depression at the back of the 
 neck in the adult. 
 
 The maxillary process is more prominent than in the preceding stages, as is 
 also the naso-optic furrow. The second arch has become larger and has grown 
 over the third and fourth, thus completely hiding them, but a depression known 
 as the preceruical sinus is left just caudal to the second arch. The first branch- 
 ial groove is relatively large and marks the site of the external auditory meatus, 
 while the surrounding portions of the first and second arches in part are 
 destined to give rise to the external ear. 
 
 Cervical flexure 
 Occipital depression 
 
 ^^^^^ Cervical depression 
 
 ^1 
 
 Cephalic flexure 
 
 "C ~\ s 
 
 Dorsal flexure 
 
 Umbilical cord 
 
 ^/ |K^__X 
 
 \. 
 
 Sacral flexure 
 
 FIG. 125. Human embryo n mm. long (31-34 days). His. 
 
 The distal portion of the upper limb bud has become flattened, and four 
 radial depressions mark the boundaries between the digits. The lower limb 
 bud is now divided by means of a constriction into a proximal and a distal 
 portion. In development the upper limb is always slightly in advance of the 
 lower. 
 
 The rotundity of the abdomen, due to the rapidly growing heart and liver, 
 is more pronounced than in the preceding stages. 
 
 Fig. 126 shows a stage in which the crescentic form of the body, as seen in 
 profile, is not so apparent. This is due principally to the partial straightening 
 of the cervical flexure and to the greater rotunditv of the abdomen. The 
 
TEXT-BOOK OF EMBRYOLOGY. 
 
 cervical depression is deeper, and the neck region in general is fairly well 
 differentiated. 
 
 The ventral part of the first branchial arch has fused with the ventral part 
 of the second, leaving the dorsal part of the first groove open to form the ex- 
 ternal auditory meatus. The parts surrounding the meatus bear more resem- 
 blance to the concha of the ear. The mandibular process of the first arch has 
 become differentiated in part into the lower Up and chin regions. The ventral 
 (distal) end of the maxillary process represents the region of the upper lip. The 
 
 FIG. 126. FIG. 127. 
 
 FIG. 126. Human embryo of 15.5 mm. (39-40 days). His. 
 FIG. 127. Human embryo of 16 mm (42-45 days). His. 
 
 nose is apparent as a short process extending from the fore-brain region toward 
 the upper lip. 
 
 The limb buds are turned more nearly at right angles to the long axis of the 
 body. The radial depressions which were present on the flattened distal por- 
 tion of the upper limb in the preceding stage are now continuous with depres- 
 sions around the distal border. Similar radial depressions are also present on 
 the distal portion of the lower limb. The tail is smaller in proportion to the 
 rest of the embryo. 
 
DEVELOPMENT OF THE EXTERNAL FORM OF THE BODY. 
 
 145 
 
 After the stage shown in Fig. 126 the cervical flexure continues to dimm- 
 ish, so that the head comes to lie nearly in a direct line with the body (Fig. 127). 
 The rotundity of the abdomen diminishes owing to the fact that the heart and 
 liver grow more slowly relatively to the body as a whole. The tail, which was 
 still a prominent feature in Fig. 125, continues to become less prominent in the 
 succeeding stages (Figs. 127, 128, 129, 130). This is not due so much to an 
 actual atrophy of the tail as to an increase in the size of the buttocks. In the 
 adult the only remnant of the tail is the coccyx. 
 
 128. 
 
 FIG. 129. 
 
 FIG. 130. 
 
 FIG. 128. Human embryo of 17.5 mm. (47-51 days). His. 
 FIG. 129. Human embryo of 18.5 mm. (52-54 days). His. 
 FIG. 130. Human embryo of 23 mm. (2 months). His. 
 
 During the second month of development the external genitalia become very 
 prominent and the sexes can be easily differentiated. 
 
 By the end of the second month the embryo has acquired a form which 
 resembles in a general way the form of the adult (Fig. 130). From this time on 
 it is customary to speak of the growing organism as & foetus. 
 
 Branchial Arches Face Neck. 
 
 At a very early stage (embryos of 2-4 mm.) certain peculiar structures 
 appear in that part of the embryo which is destined to become the face and neck 
 regions. They are at first noticeable as slit-like depressions nearly at right 
 angles to the long axis of the body. In an embryo 2.15 mm. long two of these 
 depressions are visible (Fig. 121). Shortly after this a third and then a fourth 
 
146 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 appears. At the same time elevations appear between the succeeding depres- 
 sions, the first elevation appearing cranial to the first depression. (Compare 
 Figs. 122, 123.) The elevations are the branchial arches and the depressions are 
 the branchial grooves. Corresponding elevations and depressions also mark the 
 
 FIG. 131, 
 
 FIG. 132. 
 
 FIG. 131. Human embryo of 78 mm. (3 months). Minot. 
 FIG. 132. Human embryo of 155 mm. (123 days). Minot. 
 
 interior of the pharynx, so that the portions of the wall of the pharynx which 
 correspond to the grooves are thin as compared with those portions which cor- 
 respond to the arches. 
 
 The arches develop in order from the first to the fourth; consequently they 
 are successively smaller from the first to the fourth (Fig. 122). The conditions 
 
DEVELOPMENT OF THE EXTERNAL FORM OF THE BODY. 147 
 
 change rapidly, so that in embryos of 9-10 mm., the third and fourth arches have 
 sunk inward, thus producing a depression known as the preceruical sinus. 
 Soon after this the second arch enlarges, grows over the sinus, and, fusing with 
 the underlying arches, fills up the depression. 
 
 The ventral end of the first arch fuses with the ventral part of the second 
 across the ventral part of the first groove. The dorsal part of the first groove is 
 thus left open and becomes the external auditory meatus. A part of the second 
 arch, together with a part of the first arch bounding the first groove on the 
 cranial side, is transformed into the concha of the ear (Figs. 123, 125, 126). 
 
 The first branchial arch becomes the 
 largest and undergoes profound changes 
 which are extremely important in the de- 
 velopment of the face region. Earlier in 
 this chapter (p. 139) it was stated that the 
 cephalic flexure caused the fore-brain to 
 project ventrally at a right angle to the long 
 axis of the body, and that between the pro- 
 jecting fore-brain and the heart a distinct 
 depression or pit the oral fossa was pres- 
 ent. Soon after the appearance of the first 
 arch a strong process the maxillary process 
 develops on its cranial side (Fig. 122). 
 The main portion of the arch, which may 
 be now called the mandibular process, 
 rapidly increases in size, extends ventrally 
 and finally meets and fuses with its fellow 
 of the opposite side in the midventral line 
 (Fig. 134). The result of the enlargement 
 of the first arch and its process is that they 
 
 . . . , , . FIG. 133. Human embrvo of 4 months. 
 
 are interposed between the heart and the Natural size. Koiimann. 
 
 fore-brain vesicle, thus bounding the oral 
 
 fossa laterally (Fig. 122). During this time the heart is gradually moving 
 caudally. Meanwhile a process the naso-frontal process grows ventrally 
 from the medial portion of the fore-brain region and comes in contact laterally 
 with the maxillary process. Along the line of contact a furrow is left, which 
 extends obliquely to the region of the optic vesicle and is known as the naso- 
 optic furrow (Fig. 134). 
 
 The various structures which have been mentioned bound the oral fossa 
 which has become a deep quadrilateral pit. Cranially (above) the fossa is 
 bounded by the broad, rounded, unpaired naso-frontal process; caudally (below) 
 it is bounded by the mandibular processes; laterally it is bounded by the maxil- 
 
148 TEXT-BOOK OF EMBRYOLOGY. 
 
 lary processes, and to a slight extent by the mandibular processes. Between 
 the maxillary and mandibular processes on each side a notch marks the angle 
 of the mouth. 
 
 As development proceeds these structures become more elaborate and enter 
 into more intimate relations with one another. The naso-frontal process 
 extends farther downward toward the mandibular processes, so that the 
 oral fossa becomes more nearly enclosed and the entrance to it reduced to a 
 crescent-shaped slit the mouth slit. At the same time two secondary processes 
 develop on each side from the naso-frontal process. One of these the 
 medial nasal process forms near the medial line; the other the lateral nasal 
 process forms more laterally (Figs. 135, 136). Between the two processes there 
 
 Cerebral hemisphere 
 
 Lat. nasal process 
 Nasal pit 
 
 Med. nasal process ^^^Bi^^kfl&JB Naso-optic furrow 
 Angle of mouth M^ || Maxillary process 
 
 Mandibular 
 
 FIG. 134. Ventral view of head of 8 mm. human embryo. His. 
 
 is a depression the nasal pit which marks the entrance to the future nasal 
 cavity. The maxillary process on each side grows farther toward the medial 
 line and comes in contact with the lateral and medial nasal processes. 
 
 At this stage all the elements which enter into the fundamental structure of 
 the face region are present. Further development consists essentially of 
 fusions between these various elements. 
 
 The two medial nasal processes come closer together to form the single 
 medial process which gives rise to the medial portion of the upper lip and to the 
 adjoining portion of the nasal septum. The maxillary process on each side 
 fuses with the corresponding lateral and medial nasal processes. This 
 fusion obliterates the naso-optic furrow and also shuts off the communi- 
 cation between the mouth slit and the nasal pit (Figs. 136, 137). The lateral 
 nasal process gives rise to the wing of the nose; the maxillary process gives rise 
 
DEVELOPMENT OF THE EXTERNAL FORM OF THE BODY. 
 
 149 
 
 to the major part of the cheek and the lateral portion of the upper lip. The 
 fusion between the maxillary and nasal processes, as seen on surface view, is 
 coincident with and a part of J;he separation of the nasal cavity from the oral 
 cavity (see page 319). The nose itself is at first a broad, flat structure, but 
 later becomes elevated above the surface of the face, with an elongation and a 
 narrowing of the bridge. 
 
 Mid-brain 
 
 Cerebral hemisphere 
 
 Lat. nasal process 
 Nasal pit 
 
 Med. nasal process 
 Angle of mouth 
 
 Eye 
 
 Naso-optic furrow 
 
 Maxillary process 
 
 B Mandibular process 
 
 Branchial grooves 
 
 ^B Branchial arch II 
 
 FIG. 135. Ventral view of head of 113 mm. human embryo. Rabl. 
 
 The lower jaw, lower lip and chin are formed by the mandibular processes of 
 the first branchial arch (Figs. 134, 136, 137). At first the chin region is rela- 
 tively short, but broad in a transverse direction. Later it becomes longer and a 
 transverse furrow divides the middle portion into lower lip and chin (Fig. 137). 
 
 The Extremities. 
 
 The limb buds appear in human embryos about the end of the third week as 
 small, rounded protuberances on the ventro-lateral surface of the body. The 
 upper limb buds arise just caudal to the level of the cervical flexure, the lower 
 opposite the sacral flexure (Figs. 123, 124). The upper appear first, the lower 
 following shortly, and the difference in time in the appearance of the upper 
 and lower buds is followed by a difference in degree of development, the 
 upper extremities maintaining throughout f cetal life a slight advance in develop- 
 ment over the lower. 
 
150 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 During the fourth week the limb buds become elongated, and each bud 
 becomes divided by a transverse constriction into a proximal and a distal por- 
 tion (Figs. 124, 125). The proximal portion remains cylindrical, while the 
 
 Nasa fossa 
 
 Naso-optic furro 
 Mouth slit 
 
 Branchial groove I """I 
 
 Cerebral hemisphere 
 
 Naso-frontal process 
 Lateral nasal process 
 Medial nasal process 
 Maxillary process 
 
 Mandibular process 
 
 FIG. 136. Ventral view of head of 13.7 mm. human embryo. His. 
 
 distal portion becomes somewhat broader and considerably flattened. Dur- 
 ing the fifth week the digits appear (see below) . During the sixth week the 
 proximal portion of each bud is subdivided by a transverse constriction into 
 two segments (Fig. 127). Thus each extremity as a whole is divided into three 
 
 Branchial groove I 
 (external ear) 
 
 Nose 
 
 Lat. nasal process 
 Maxillary process 
 
 Med. nasal process 
 
 FIG. 137. Ventral view of head of human embryo of 8 weeks. His. 
 
 segments each upper, into arm, forearm and hand, each lower, into thigh, leg 
 and foot. 
 
 The anlagen of the digits (fingers and toes) appear, during the fifth week, in 
 the broader, flattened distal portions of the limb buds. The boundaries be- 
 
DEVELOPMENT OF THE EXTERNAL FORM OF THE BODY. 151 
 
 tween the anlagen are marked by radial depressions on the flat surfaces; the 
 anlagen themselves are the elevations between the depressions (Figs. 125, 126). 
 The anlagen grow rapidly in thickness and length, thus producing not only an 
 apparent deepening of the radial depressions but also indentations around the 
 distal free borders of the limb buds (Fig. 126). The depressed areas produce a 
 web-like structure between the digits, resembling the web in some aquatic 
 animals. The web does not keep pace with the digits, however, and is soon 
 confined to the proximal ends of the latter. In length the fingers grow slightly 
 more rapidly than the toes and thus become somewhat longer. From the 
 seventh week on, the thumb and great toe become more and more widely sepa- 
 rated from the index finger and the second toe respectively (Figs. 128, 130, 131). 
 
 As the limb buds become elongated during the earlier stages of development, 
 they assume a position with their long axes nearly parallel with the long axis of 
 the body, and are directed caudally (Fig. 125). In later stages they are directed 
 ventrally and their long axes are nearly at right angles to the long axis of the 
 body (Fig. 126). The radial margins of the upper extremities are turned 
 toward the head, as are the tibial margins of the lower. The palmar surfaces 
 of the hands and the plantar surfaces of the feet are turned inward or toward 
 the body. The elbow is turned slightly outward and toward the tail, the knee 
 slightly outward and toward the head. From these conditions it may be con- 
 cluded that the radial side of the upper extremity is homologous with the tibial 
 side of the lower; that the palmar surface of the hand is homologous with the 
 plantar surface of the foot; and that the elbow is homologous with the knee. 
 
 In order to acquire the position relative to the body as found in postnatal 
 life, the extremities must undergo further changes. These consist essentially 
 of tortions around their long axes. The right upper extremity turns to the 
 right, the right lower turns to the left. The left upper extremity turns to the 
 left, the left lower turns to the right. At the same time the extremities rotate 
 through an angle of ninety degrees and again come to lie parallel with the long 
 axis of the body. The result is that the radial sides of the upper extremities are 
 turned outward (away from the sagittal plane of the body) and the tibial sides 
 of the lower are turned inward (toward the sagittal plane of the body) . In the 
 upper extremity this is, of course, the supine position in which the radius and 
 ulna are parallel. 
 
 Age and Length of Embryos. 
 
 AGE. Certain general conclusions regarding the age of embryos have been 
 formulated by His (Anatomic menschlicher Embryonen, 1882) and accepted 
 for the most part by embryologists. These as stated by His are as follows: 
 
 i. Development begins at the time of impregnation, that is, at the moment 
 when the male sexual element enters the ovum and fertilizes it. 
 
152 TEXT-BOOK OF EMBRYOLOGY. 
 
 2. The time the ovum leaves the ovary is determined by the menstrual 
 period, but the rupture of the (Graafian) follicle is not necessarily coincident 
 with the beginning of hemorrhage; it may occur two or three days before or it 
 may occur during hemorrhage. 
 
 3. The egg is not capable of being fertilized at any point in its course from 
 the ovary to the uterus, but only in the upper part of the oviduct. 
 
 4. The spermatozoa which have entered the female sexual organs must 
 await the ovum in the upper part of the oviduct, and can retain their vitality 
 here for several days or possibly for several weeks; the time of cohabitation, 
 therefore, does not stand in direct relation to the age of the embryo. 
 
 5. In the majority of cases the age of the embryo can be estimated from the 
 beginning of the first menstrual period which has lapsed. It is possible, how- 
 ever, for menstruation to occur after fertilization of the ovum. 
 
 6. The age of the embryo can be expressed thus : age = X M, or age = 
 X M 28. X is the date of the abortion and M is the beginning of the last 
 menstrual period. The second formula is used where it is necessary to estimate 
 from the beginning of the first period which has lapsed. 
 
 There is no doubt whatever that the age of the embryo must be dated from 
 the time of fertilization of the ovum; but owing to the fact that the time of 
 fertilization of the human ovum is not known, the exact age cannot be deter- 
 mined. Even when the date of coitus and the time of cessation of the menses 
 are known, the uncertainty regarding the time of ovulation and the time re- 
 quired by the spermatozoa to reach the upper end of the oviduct must be 
 taken into consideration. It is now generally conceded that ovulation and 
 menstruation are coincident in the majority of cases, but, on the other hand, 
 ovulation is known to occur sometimes independently of the menstrual periods 
 (see also p. 29). 
 
 In addition to the uncertainty regarding the time when development 
 begins there is also an uncertainty as to the time when the embryo ceases to 
 develop. For in most cases the embryos are abortions and the death of the 
 embryo does not necessarily precede immediately its expulsion from the uterus. 
 
 It is convenient, however, for practical purposes, to have some means of 
 approximating the age of an embryo. His' formulae serve to determine the age 
 within certain limits. It is obvious from these formulae that there is a possibility 
 of an error of twenty-eight days in the estimate. Yet in the earlier stages of 
 development (during the first three months) the error can be corrected after 
 examination of the embryo, since there is no difficulty in recognizing the differ- 
 ence, for example, between an embryo two weeks old and one six weeks old. 
 
 LENGTH. Many German authors employ two different methods for 
 measuring embryos at different periods. One of these methods they use 
 in measuring embryos between 4 and 14 mm., when the body is much curved. 
 
DEVELOPMENT OF THE EXTERNAL FORM OF THE BODY. 153 
 
 The length of the embryo is considered as the length of a straight line drawn 
 from the apex of the cervical flexure to the apex of the sacral flexure (neck- 
 rump length, Nackensteisslange; see Fig. 124). During the second month and 
 later, or in embryos of more than 20 mm., the body becomes more nearly 
 straight and the measurement is taken along a straight line from the apex of the 
 cephalic flexure to the apex of the sacral flexure (crown-rump length, Scheitel- 
 steisslange; see Fig. 126). 
 
 Owing to the changes in curvature of embryos during development, no 
 one system of measurement will give uniform results for all stages. In this 
 country it is the general practice to measure the greatest length of the embryo, 
 in its natural attitude, along a straight line. The measurement does not 
 of course include the extremities. At certain stages this length corresponds 
 with the neck-rump length, at other stages with the crown-rump length, at still 
 other stages with neither. 
 
 RELATION OF AGE TO LENGTH. Not infrequently the history of an embryo 
 is not obtainable, and in such cases the age must be inferred from w r hat is known 
 concerning the relation of the age to the length of the embryo. The age can be 
 computed approximately by this means, although there is a possibility of error. 
 Embryos of the same age are not necessarily of the same length, since conditions 
 of nutrition, etc., determine not only the size of the embryo but also the degree 
 of its development. In the later stages of development the limit of error is not 
 so important, but in the younger stages the difference of a day or two means 
 much. 
 
 His estimated the ages of a number of embryos from available data as 
 follows : 
 
 Embryos of 2-2 J weeks measure 2.2-3 mm. (neck-rump length). 
 
 Embryos of 2^-3 weeks measure 3-4.5 mm. (neck-rump length). 
 
 Embryos of 3^ weeks measure 5-6 mm. (neck-rump length). 
 
 Embryos of 4 weeks measure 7-8 mm. (neck-rump length). 
 
 Embryos of 4j weeks measure 10-11 mm. (neck-rump length). 
 
 Embryos of 5 weeks measure 13 mm. (neck-rump length). 
 
 More recent researches on the rate of development in the lower Mammals 
 tend to show that development proceeds relatively slowly during the earliest 
 stages, and then goes on with increasing rapidity for a time. In the rabbit, for 
 example, it has been shown that the embryonic disk is but slightly differentiated 
 at the seventh and eighth days, while at the tenth day the embryo possesses 
 branchial grooves and primitive segments. If this peculiarity in the rate of 
 development occurs in the human embryo, the ages assigned to the earlier 
 embryos by His must be increased. 
 
 Mall's formulae for estimating age, deduced from observations on a large 
 number of embryos, are as follows: In embryos of i-ioo mm. the age in days 
 
154 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 can be expressed fairly accurately by the square root of the length multiplied by 
 100 (Jlength in mm. x 100). In embryos between 100 and 220 mm. the age 
 in days is about the same as the length in millimeters. 
 
 Some of the most important embryos which have been described are 
 listed in the accompanying table, no pretense being made of giving a complete 
 list. The table is compiled largely from the more extensive tables of Mall 
 and merely serves to indicate some of the younger embryos with fairly well- 
 known histories, from which certain conclusions have been drawn concerning 
 the relation of age to length. The periodicals in which descriptions may be 
 found are given with the authors' names in " References for Further Study" 
 at the end of this chapter. 
 
 No. 
 
 Observer 
 
 Dimensions of chori- 
 onic vesicle in 
 millimeters 
 
 Number 
 of days be- 
 tween last 
 menstrual 
 period and 
 abortion 
 
 Number of days 
 between first 
 lapsed period 
 and abortion 
 
 Probable 
 age in days 
 
 Length of 
 embryo in 
 millimeters 
 
 i 
 
 2 
 
 Bryce-Teacher 
 Leopold 
 
 1.9 x i.i x .95 
 i 4 x 9 x 8 . 
 
 38 
 
 10 
 
 13-14 
 
 0-15 
 
 3 
 
 Peters 
 Reichert 
 
 3. xi. 5 xi. 5 
 
 r r v -7 3 
 
 3 
 
 A 2 
 
 14. 
 
 Id 
 
 0.19 
 
 5 
 6 
 
 von Spec 
 Mall 
 
 7-5X.5-5 
 
 IO C. X 7 X 7 
 
 35 
 
 4.1 
 
 1 1 
 
 12 
 
 1 1 
 
 -37 
 08 
 
 7 
 
 Eternod 
 
 10 8 x 8 2 x 6 
 
 
 
 
 J -3 . , 
 
 8 
 
 von Spee 
 
 10 x 8 *\ x 6 5 
 
 y r 
 
 
 I 2 
 
 1 e i 
 
 
 Mall 
 
 18 x 18 x 8 
 
 4.1 
 
 I 3 
 
 I 7 
 
 21 
 
 10 
 
 ii 
 
 Thomson 
 His 
 
 5-7 
 
 I C X I 2 5J 
 
 42 
 
 4O 
 
 14 
 I 2 
 
 14 
 
 12 
 
 2.1 
 
 2 I <.. . 
 
 12 
 
 Thomson 
 
 15 x 10 
 
 14- 
 
 
 14 
 
 2.Z. . . 
 
 13 
 14 
 
 von Spee. 
 Janosik 
 
 i5 x H 
 8 
 
 42 
 
 4.-J 
 
 14 
 
 If . 
 
 14 
 T.Z. . 
 
 2.69 
 
 1C 
 
 His 
 
 14 x ii 
 
 48 
 
 2O 
 
 2O 
 
 3.2 
 
 16 
 
 Mall 
 
 24 x 16 x 9 
 
 4.2 
 
 
 14. 
 
 4 
 
 17 
 
 His 
 
 JQ X 2< 
 
 C I 
 
 
 2? 
 
 
 18 
 
 His 
 
 2C x 2O 
 
 21 
 
 
 21 
 
 r . 
 
 10 
 
 M^eyer 
 
 22 
 
 18 
 
 
 18 
 
 r 2 . 
 
 20 
 21 
 
 Stubenrauch . . 
 Mall . . 
 
 2H X 2< 
 
 45 
 
 ET2 
 
 17 
 24 
 
 17 
 24 .... 
 
 6 
 
 7. . 
 
 22 
 
 His 
 
 21 X 17 
 
 C7 
 
 20 (?) 
 
 27 . 
 
 7 7 c 
 
 23 
 
 Meyer 
 
 4C 
 
 28 
 
 
 28 
 
 8 
 
 24 
 
 Ecker 
 
 
 60 
 
 2,2. . 
 
 32. . 
 
 IO 
 
 2 S 
 
 His 
 
 30 x 27 
 
 61 
 
 22. . 
 
 73 
 
 II 
 
 26 
 
 His 
 
 35x28 
 
 61 
 
 35 
 
 35 
 
 13-6 
 
 Normal, Abnormal and Pathological Embryos. 
 
 In the majority of cases of spontaneous abortion it is not possible to examine 
 the uterus; but in those cases where it is possible, examination frequently shows 
 abnormal or pathological conditions. As might be expected, the embryos 
 obtained from abnormal or pathological uteri very frequently show anom- 
 alous conditions or pathological changes, or both. Since many of the 
 
DEVELOPMENT OF THE EXTERNAL FORM OF THE BODY. 155 
 
 human embryos obtained are the results of spontaneous abortions, there is 
 reason to suspect that such embryos are not normal. To the physician, as 
 well as to the embryologist, it is important, therefore, that there should be some 
 criteria for differentiation between normal and abnormal or pathological 
 embryos. 
 
 Gross anomalies, or monstrosities, such as cases in which the head or some 
 other member of the body is lacking, or in which the head is disproportionately 
 large or disproportionately small, or in which two embryos are directly united, 
 or in which the foetal membranes are partially lacking, or in which the mem- 
 branes are present and the embryo wholly or partially lacking, and many other 
 anomalous conditions, can, of course, be recognized at once. Extensive 
 pathological changes or processes of disintegration in the tissues of the em- 
 bryo or foetal membranes are also easily recognized. But there are many less 
 obvious anomalies and pathological conditions which, nevertheless, are im- 
 portant. Such cases are most difficult to differentiate. 
 
 The fcetal membranes not infrequently are useful in determining whether 
 an embryo has followed the normal course of development. During the first 
 month the amnion invests the embryo rather closely when development is 
 normal. If the amniotic sac is disproportionately large, however, it is a mark 
 of abnormal or pathological changes. In some cases an amniotic sac 50 to 60 
 mm. in diameter contains an embryo but a few millimeters in length. In the 
 earlier stages of development, before the amnion enlarges sufficiently to reach 
 the chorion, there is present a delicate network of fibrils, the magma reticulare, 
 which is attached to both chorion and amnion and which serves as a sort of 
 anchor for the amnion. In abnormal or pathological cases the magma reticu- 
 lare may become wholly or partially fluid or granular, or may become greatly 
 increased in amount. It may even extend through the amnion and reach the 
 embryo itself. 
 
 Normal human as well as other mammalian embryos in the fresh condition 
 are more or less transparent, and such structures as the heart, the larger blood 
 vessels, the liver, and the brain vesicles can be seen through the skin. If the 
 embryo has been dead for some time or has undergone pathological or degen- 
 erative changes, the transparency is lost. 
 
 Where pathological or degenerative changes in the embryo or its membranes 
 are suspected but cannot be definitely determined by macroscopic examination, 
 recourse may be had to sectioning and staining. 
 
 References for Further Study. 
 
 VAX BEXEDEX, E.: Recherches sur les premiers stades du developpement du Murin 
 (Vespertilio murinus). Anat. Anz., Ed. XVI, 1899. 
 
 BRYCE, T. H. and TEACHER, J. H.: AD Early Human Ovum Imbedded in the Decidua. 
 Mac Lehose & Sons, Glasgow, 1908. 
 
156 TEXT-BOOK OF EMBRYOLOGY. 
 
 ECKER, A.: Beitrage zur Kenntniss der ausseren Formen jiingster menschlichen Embryo- 
 nen. Archiv. f. Anat. u. PhysioL, Anat. Abth., 1880. 
 
 ETERNOD, A. C. F.: Communication sur un oeuf avec embryon excessivernent jeune. 
 Arch. ital. de Biol. SuppL 12 et 14, 1894. 
 
 ETERNOD, A. C. F.: Sur un oeuf humain de 16.3 mm. avec embryon de 2.1 mm. Arch, 
 des. sci. phys. et nat. t Vol. II, 1896. 
 
 His, W. : Anatomic menschlicher Embryonen. With Atlas. 1880-1885. 
 
 His, W.: Die Entwickelung der menschlichen und tierischen Physiognomien. Arch. /. 
 Anat. u. PhysioL, Anat. Abth., 1892. 
 
 jAN6siK, J.: Zwei junge menschliche Embryonen. Arch. /. mik. Anat., Bd. XXX, 1887. 
 
 KEIBEL, F.: Ein sehr junges Menschliches Ei. Arch. f. Anat. u. PhysioL, Anat. Abth., 
 1890. 
 
 KEIBEL, F.: Entwickelung der ausseren Korperform der Wirbeltierembryonen. In 
 Hertwig's Handbuch der vergleich. u. experiment. Entwickelungslehre der Wirbeltiere. Bd. I, 
 Teil I, 1906. 
 
 KEIBEL, F., and ELZE, C.: Normentafcl zur Entwickelungsgeschichte des Menschen. 
 Jena, 1908. 
 
 KEIBEL, F., and MALL, F. P.: Manual of Human Embryology. Vol. I, 1910. 
 
 KOLLMANN, J. : Die Korperform menschlicher normaler und pathologischer Embryonen. 
 Arch. f. Anat. u. PhysioL, Anat. Abth. SuppL, 1889. 
 
 KOLLMANN, J.: Handatlas der Entwickelungsgeschichte des Menschen. Jena, 1907. 
 
 LEOPOLD, G.: Ueber ein sehr junges menchliches Ei. Leipzig, 1906. 
 
 MALL, F. P.: A Human Embryo Twenty-six Days Old. Jour, of MorphoL, Vol. V, 
 1891. 
 
 MALL, F. P.: A Human Embryo of the Second Week. Anat. Anz., Bd. VIII, 1893. 
 
 MALL, F. P. : Human Embryos. Wood's Reference Handbook of the Medical Sciences, 
 Vol. Ill, 1901. 
 
 MEYER, H.: Die Entwickelung der Urnieren beim Menschen. Arch. f. mik. Anat.,. 
 Bd. XXXVI, 1890. 
 
 PETERS, H.: Ueber die Einbettung des menschlichen Eies, und das fruheste bisher 
 bekannte menschliche Placentarstadium. Leipzig und Wien, 1899. 
 
 RABL, C.: Die Entstehung des Gesichtes. I. Heft. Leipzig, 1902. Folio. 
 
 REICHERT, B.: Beschreibung einer fruhzeitigen menschlichen Frucht. Abhandl. 
 preuss. Akad., Berlin, 1873. 
 
 SELENKA, E.: Studien iiber die Entwickelungsgeschichte der Tiere; (Menschenaffen). 
 Wiesbaden, 1908. Parts 8 to 10. 
 
 VON SPEE, GRAF: Beobachtungen an einer menschlichen Keimscheibe mit offener 
 Medullarrinne und Canalis neurentericus. Arch. f. Anat. u. PhysioL, Anat. Abth., 1889. 
 
 VON SPEE, GRAF: Ueber friihe Entwickelungsstufen des menschlichen Eies. Arch. /, 
 Anat. u. PhysioL, Anat. Abth., 1896. 
 
 STUBENRAUCH: Inaug. Dissert. Miinchen, 1889. 
 
 THOMPSON, A.: Contributions to the History of the Structure of the Human Ovum 
 Before the Third Week after Conception, with a Description of Some Early Ova. Edin- 
 burgh Med. and Sur g. Journal, Vol. Ill, 1839. 
 
PART II. 
 
 ORGANOGENESIS. 
 
CHAPTER IX. 
 
 THE DEVELOPMENT OF THE CONNECTIVE TISSUES AND THE 
 
 SKELETAL SYSTEM. 
 
 All the connective or supporting tissues of the body, except neuroglia, 
 are derived from the mesoderm. This does not imply, however, that all the 
 mesoderm is transformed into connective tissues; for such structures as the 
 endothelium of the blood vessels and lymphatic vessels, probably blood itself, 
 the epithelium lining the serous cavities, smooth and striated muscle, and a part 
 of the epithelium of the urogenital system are derived from mesoderm. 
 
 Primitive groove 
 
 Ectoderm 
 
 Mesoderm 
 
 Entoderm 
 
 FIG. 138. Transverse section of chick embryo of 27 hours' incubation. Photograph. 
 
 The origin of the mesoderm itself has been discussed elsewhere (p. 81). 
 In this connection it is sufficient to recall that it is situated between the ectoderm 
 and entoderm and consists of several layers of closely packed cells (Fig. 138). 
 The axial portion in the neck and body regions becomes differentiated into the 
 mesodermic somites. At the same time a cleft (the ccelom) separates the more 
 peripheral portion into a parietal and a visceral layer (Figs. 139 and 141). In 
 the head region where, in the higher animals, there is little or no indication of 
 
 161 
 
162 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 Ectoderm 
 
 Ectoderm 
 
 Coelom 
 
 FIG. 139. Transverse section of chick embryo (2 days' incubation). Photograph. 
 The parietal mesoderm (lying above the ccelom) is not labeled. The two large vessels under 
 the primitive segments are the primitive aortae. Spaces separating germ layers are due to 
 shrinkage. 
 
 Mesoderm 
 (mesenchyme) 
 
 Neural tube 
 
 Ectoderm 
 
 Pharynx 
 
 Entoderm 
 
 FIG. 140. Transverse section through head region of chick embryo of 42 hours' 
 incubation. Photograph. 
 
THE CONNECTIVE TISSUES AND THE SKELETAL SYSTEM. 
 
 163 
 
 somites and ccelom, the mesoderm simply fills in the space between the ecto- 
 derm and entoderm (Fig. 140). Portions of the mesoderm in all these re- 
 gions are destined to give rise to connective tissues. Each mesodermic somite 
 soon becomes differentiated into three parts the sclerotome, cutis plate and 
 myotome (Fig. 142). Of these, only the sclerotome and cutis plate are directly 
 concerned in the formation of connective tissues, the myotomes giving rise to 
 striated voluntary muscle. The sclerotomes are destined to give rise to the 
 
 Neural tube 
 
 Intermediate 
 cell mass 
 
 Notochord j 
 
 Entoderm .<t^w f^\ 
 
 ^r\"C_ 
 
 f T ! 
 
 -^L __ *. 
 
 Visceral mesoderm 
 
 Primitive segment 
 
 Intermediate 
 cell mass 
 
 I Ectoderm 
 
 Parietal 
 mesoderm 
 
 v-"* ffg) Lateral 
 *~(jf~~ body wall 
 
 Mesothelium 
 
 Umbilical vein 
 
 FIG. 141. Transverse section of human embryo with 13 primitive segments; section taken 
 through the 6th segment. Kollmann. 
 
 vertebrae and other forms of connective tissue in their neighborhood, the cutis 
 plates to a part, at least, of the corium of the skin. The parietal and visceral 
 layers of the mesoderm (except the mesothelium lining the ccelom) and the 
 mesoderm of the head region are destined to give rise to the various types of 
 connective tissue forming parts of the other organs of the body. 
 
 HISTOGENESIS. 
 
 The sclerotomes and cutis plates at first constitute parts of the mesoaermic 
 somites, and are composed of epithelial-like cells with little intercellular sub- 
 stance. The intercellular substance gradually increases in amount so that the 
 
164 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 Myotome 
 
 Pronephros - 
 
 Parietal mesoderm 
 Intestine 
 
 Umbilical 
 
 Vein 
 
 Visceral mesoderm 
 
 FIG. 142. ^Transverse section of human embryo of the 3rd week. Sc/. 1 , Break in myotome at 
 point where sclerotome is closely attached. Kollmann. 
 
 Neural tube 
 
 Intersegmental 
 artery 
 
 Intersegmental 
 artery 
 
 Ectoderm 
 
 Sfc/i/^ Sclerotome 
 
 Myocoel 
 
 FIG. 143. Three primitive segments from sagittal section of human embryo of 
 the 3rd week. Kollmann. 
 
THE CONNECTIVE TISSUES AND THE SKELETAL SYSTEM. 165 
 
 cells become more widely separated from one another, at the same time 
 assuming oval or spindle shapes and then irregular branching forms (Fig. 
 144). The rest of the mesoderm, except the mesothelium, also undergoes a 
 similar transformation so that structurally its cells are indistinguishable from 
 those derived from the sclerotomes and cutis plates. 
 
 Thus the mesoderm at this stage is composed of irregular, branching 
 cells, with a relatively large amount of homogeneous intercellular substance 
 filling the interstices. The branches, or protoplasmic processes, of each 
 cell anastomose freely with those of other cells in the immediate vicinity. 
 
 I 
 
 
 FIG. 144. Mesenchymal tissue from somatopleure of a 5 mm. human embryo. 
 Mesothelium is shown along lower border of figure. 
 
 In this manner a syncytium is formed to which the term mesenchyme is ap- 
 plied (Fig. 144). The mesenchyme itself lacks specialization, being what 
 is known as an indifferent tissue, but it constitutes the structural basis upon 
 which all the connective tissues of the adult body are built ; all the forms of 
 connective tissue (except neuroglia) develop from it. 
 
 That intercellular substance is derived originally from the cell can scarcely 
 be denied. All the cells of the organism are derived from the fertilized ovum. 
 As soon as two or more cells are formed by segmentation of the ovum, they are 
 either simply in apposition or else they are united by something in the nature 
 of a " cement" substance which must have been derived from the cells them- 
 selves. In the mesenchymal tissue this intercellular ground substance is a 
 prominent feature, and probably represents in part nutritive materials and 
 in part the products of cell activity. 
 
166 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 Fibrils and Fibers. The least differentiated and perhaps the least 
 specialized tissue derived from mesenchyme is reticular tissue, such as that 
 found in the lymph nodes and spleen. In the peripheral part of the cyto- 
 plasm, or exoplasm, of the mesenchymal cells and their processes there arise 
 delicate fibrils, often extending from one cell to another, which probably 
 
 FIG. 145. Fibril forming cells from fresh subcutaneous tissue of head of chick embryo. Boll. 
 
 represent specialized parts of the spongioplasm. These fibrils maintain 
 their intracellular position instead of becoming separated from the parent 
 cytoplasm, so that the reticular tissue retains a marked resemblance in 
 form to the original mesenchyme. 
 
 FIG. 146. Connective tissue (mesenchymal) cells from larval salamander. Flemming. 
 
 The first step in the development of the true fibrillar forms of connective 
 tissue from mesenchyme is the formation of fibrils and fibers. While it has 
 been held by some investigators that the fibrils arise in and from the homo- 
 geneous intercellular substance, the best substantiated view is that they arise 
 within and from the cytoplasm of the mesenchymal cells (Figs. 145 and 146). 
 They then become separated from the cytoplasm and lie free in the " ground" 
 
THE CONNECTIVE TISSUES AND THE SKELETAL SYSTEM. 
 
 167 
 
 substance in bundles (fibers). These fibrillated fibers are collaginous in 
 character. Elastic fibers, while not fibrillated, probably have a similar 
 origin. This first step in development gives rise to a loose, delicate tissue 
 in the embryo, known as embryonal connective tissue, from which all the 
 adult forms, except reticular tissue, develop. 
 
 The areolar tissue of the adult retains many of the general characters of 
 embryonal connective tissue. The fibers, both collaginous and elastic, are 
 loosely arranged and extend in all directions. The cells (fibroblasts) are 
 fewer, however, and while they are characterized by irregular, branching 
 forms it is not known whether their processes anastomose. 
 
 FIG. 147. Longitudinal section of developing ligament from finger of 
 human foetus of 6 months. Photograph. 
 
 In any fibrous tissue, such as areolar, or the denser forms (fascia, tendons, 
 ligaments), the structure depends upon the secondary arrangement of the 
 fibers and not upon any peculiarity of origin. In all these forms the fibers 
 have the same origin, but in the denser fascia, tendons and ligaments they 
 become arranged in parallel lines (Fig. 147). 
 
 Adipose Tissue. Adipose tissue is a form of connective tissue in which 
 the fatty element replaces to a great extent the cytoplasm in many of the 
 embryonic connective tissue cells. It always develops in close relation to blood 
 
168 TEXT-BOOK OF EMBRYOLOGY. 
 
 vessels, and first appears in the axilla and groin about the thirteenth week. 
 It is formed in other places at later periods, even during adult life, but the 
 mode of development is always the same. In some of the cells in the neigh- 
 borhood of small blood vessels minute droplets of fat are deposited. The 
 origin of the fat is not known. The droplets become larger, other smaller ones 
 appear, and finally all of them coalesce to form a single large drop which practi- 
 cally fills the cell. The result of this is that the remaining cytoplasm is pushed 
 outward and forms a sort of pellicle around the fat. The nucleus also is 
 crowded outward and comes to lie flattened in the pellicle of cytoplasm (Fig. 
 
 Small artery 
 
 FIG. 148. Developing fat from subcutaneous tissue of pig embryo 5 inches long. Small 
 artery breaking up into capillary network' groups of fat cells developing in 
 embryonic connective tissue 
 
 149) . At the same time the whole fat cell increases in size and forms a relatively 
 large structure. 
 
 Fat cells usually develop in groups or masses around blood vessels (Fig. 
 148). The neighboring groups gradually enlarge and approach each other, 
 but do not fuse, thus leaving more or less fibrous connective tissue between 
 them, which constitutes the interlobular tissue seen in adult adipose tissue. 
 Among the individual cells in a lobule there is also a small amount of fibrous 
 tissue present. From the mode of development a small artery usually affords 
 the blood supply for each lobule. 
 
 Cartilage. In the different kinds of cartilage the matrix probably repre- 
 
THE CONNECTIVE TISSUES AND THE SKELETAL SYSTEM. 
 
 169 
 
 sents a modification of the "ground substance" of the original embryonic 
 tissue. The fibers in the matrix are probably derived from the cells in the 
 same manner as the fibers in the fibrillar forms of connective tissue (Fig. 150). 
 Osseous Tissue. Here again the basis for development is embryonic 
 connective tissue, although in one type of development cartilage precedes the 
 bone. Two types of ossification are recognized intramembranous and intra- 
 cartilaginous or endochondral. In intramembranous ossification calcium salts 
 are deposited in ordinary embryonic connective tissue. In intracartilagi- 
 
 Capillary 
 
 Embryonic 
 connective tissue 
 
 Arteriole 
 
 FIG. 149. Developing fat from subcutaneous tissue of pig embryo 5 inches long. Fat (stained 
 black) developing in embryonic connective tissue cells. At the right are five individual cells 
 showing stages of development from an embryonic cell to an adult fat cell. 
 
 nous ossification hyalin cartilage first develops in the same general shape as 
 the future bone and the calcium salts are afterward deposited within the mass of 
 cartilage. It is customary to speak also of another type of ossification sub- 
 periosteal in which the calcium salts are deposited under the periosteum. 
 
 INTRAMEMBRANOUS OSSIFICATION. 
 
 This is the type of ossification by which many of the flat bones of the skull 
 and face are formed. The region in which these bones are to develop consists 
 of embryonic connective tissue. At certain points in this region bundles of 
 connective tissue fibers become impregnated with calcium salts. Such areas are 
 known as calcification centers. In each of these areas the cells increase in num- 
 ber, the tissue becomes very vascular and some of the cells, becoming more or 
 less round or oval, with distinct nuclei and a considerable amount of cytoplasm, 
 
170 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 Ectoplasm with t 
 "white" fibers ^ "-- 
 
 Ground 
 substance ' 
 
 Ectoplasm / . 
 
 FlG. 150. Connective tissue cells from intervertebral disk of calf embryo; showing origin of 
 "white" and elastic fibers in protoplasm of cells. Ectoplasm represents a modified part 
 of the protoplasm. Hansen. 
 
 Osteogenetic 
 tissue 
 
 FIG. 151. Vertical section through frontal bone of human fcetus of 4 months. 
 (Intramembranous ossification.) Photograph. 
 
THE CONNECTIVE TISSUES AND THE SKELETAL SYSTEM. 171 
 
 arrange themselves in single, fairly regular rows along the bundles of calcified 
 fibers. The differentiated cells are known as osteoblasts (bone formers), and the 
 whole tissue is now known as osteo genetic tissue. Under the influence of the osteo- 
 blasts a thin layer of calcium salts is deposited between the osteoblasts and the 
 calcified fibers. In this way the first true bone is formed, and the calcification 
 center becomes an ossification center. Successive layers or lamellae of calcium 
 salts are laid down and some of the osteoblasts become enclosed between the 
 lamellae to form the bone cells (Figs. 151 and 152). The spaces in which the bone 
 cells lie are the lacuna. At the same time the fibers also are enclosed within the 
 bone and give it its characteristic fibrous structure (Fig. 152). 
 
 Such a process results in the formation of irregular, anastomosing trabeculae 
 of bone. The spaces among the trabeculae are known as primary marrow 
 
 Osteogenetis 
 
 tissue Osteoclast Lacunae 
 
 Bone 
 
 _ , - ~-J 
 
 Calcified fibers Osteoblasts 
 
 FIG. 152. From vertical section through parietal bone of human foetus of 4 months. 
 Bone cells not shown in lacunae. (Intramembranous ossification.) 
 
 spaces and contain osteogenetic tissue (Fig. 151). This type of bone, consisting 
 of irregular, anastomosing trabeculae and enclosed marrow spaces, is known as 
 spongy bone. The spongy bone thus formed is covered on its outer side by a 
 layer of connective tissue which from its position is called the periosteum 
 (Fig. 151), and which represents a part of the original embryonic connective 
 tissue membrane in which the bone was laid down. During its development 
 the periosteum becomes an exceedingly dense fibrous membrane which is closely 
 applied to the surface of the bone. 
 
 In a growing embryo, provision must be made for increase in the size of the 
 cranial cavity to accommodate the growing brain. This is accomplished in 
 the following manner : On the inner surface of the newly formed bone, large 
 multinuclear cells appear, which are known as osteoclasts (bone destroyers). 
 The osteoclasts are unusually large cells with a large number of nuclei and 
 abundant cytoplasm, and in sections can be seen lying in depressions in the 
 
172 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 bone Howslip's lacuna (Fig. 152). They apparently possess the power of 
 dissolving bone tissue. While the destruction of bone by the osteoclasts is 
 going on on the inner surface, new bone is being formed on the outer surface, 
 especially under the periosteum where the osteoblasts are most numerous. 
 Thus the layer of bone gradually comes to lie farther and farther out and the 
 cranial cavity is enlarged. So long as the cranial cavity continues to enlarge 
 
 Cartilage 
 
 Osteogenetic tissue 
 
 Intracartilaginous 
 bone 
 
 Subperiosteal 
 bone 
 
 Blood vessels 
 
 Periosteum 
 (perichondrium) 
 
 / Ossification center 
 
 Calcification zone 
 
 FIG. 153. Longitudinal section of one of the metatarsal bones of a sheep embryo. 
 (Intracartilaginous ossification.) 
 
 the new bone is of the spongy variety, but toward the end of development the 
 trabeculae become thicker and finally come together to form the compact bone 
 characteristic of the roof of the skull. The fact that the new bone laid down 
 during the enlargement of the cranial cavity is laid down under the periosteum 
 has led to the term subperiosteal ossification. The process is essentially the 
 same as in the original intramembranous ossification. 
 
 INTRACARTILAGINOUS OSSIFICATION. 
 
 In this type of ossification hyalin cartilage is first formed in a shape which 
 corresponds very closely to the shape of the future bone. For example, the 
 femur is first represented by a piece of hyalin cartilage which develops from 
 
THE CONNECTIVE TISSUES AND THE SKELETAL SYSTEM. 173 
 
 the original embryonic connective tissue. On the surface of the cartilage a 
 membrane of dense fibrous connective tissue, known as the perichondrium, 
 develops (Fig. 153). In most cases, ossification begins about the middle 
 of the piece of cartilage, corresponding to the middle of the shaft of a long 
 bone (Fig. 153). The cell spaces enlarge and in some cases the septa of matrix 
 between the enlarged spaces break down, so that several cells may lie in one 
 space. The cell spaces radiate from a common center, but a little later they 
 come to lie in rows parallel with the long axis of the mass of cartilage. During 
 these early changes lime salts are deposited in the matrix of the cartilage in 
 this region, and the portion so involved is known as a calcification center. 
 
 So far the process is preparatory to actual bone formation. Then small 
 blood vessels from the perichondrium (periosteum) grow into the cartilage, 
 
 Periosteal bud 
 
 Cartilage 
 cell spaces ^~~^r^ ^-^ ^ Cartilage cells 
 
 
 * /^ Hk ^ Cartilage matrix 
 
 t^&3I^^^;^^Si~3feE^=a^iSF. 
 
 Periosteum 
 (Perichondrium) 
 
 FIG. 154. From section of one of the tarsal bones of a pig embryo Showing periosteal bud 
 pushing into the cartilage at the ossification center. (Intracartilaginous ossification.) 
 
 carrying with them some of the embryonic connective tissue. These little 
 ingrowths of connective tissue and blood vessels are known as periosteal buds 
 (Fig. 154). The septa between the enlarged cartilage cell spaces break down 
 still further, forming still larger spaces into which the periosteal buds grow. 
 Many of the connective tissue cells are transformed into osteoblasts oval or 
 round cells with distinct nuclei and a considerable amount of cytoplasm and 
 with the fibers and blood vessels constitute osteo genetic tissue (Fig. 155). The 
 cartilage cells in this region disintegrate and disappear, and the cavity formed 
 by the coalescence of the cell spaces constitutes the primary marrow cavity (Fig. 
 155). From the primary marrow cavity osteogenetic tissue pushes in both 
 directions toward the ends of the cartilage. The transverse septa between the 
 enlarged cartilage cell spaces break down, leaving a few longitudinal septa 
 which form the walls of long anastomosing channels which are continuous with 
 
174 TEXT-BOOK OF EMBRYOLOGY. 
 
 the primary marrow cavity. The osteoblasts arrange themselves in rows along 
 the septa of calcined cartilage and a thin layer or lamella of calcium salts is 
 deposited between them and the cartilage. Successive lamellae are deposited 
 in the same manner and some of the osteoblasts become enclosed to form bone 
 cells (Fig. 156). The cartilage in the center gradually disappears. This 
 region where bone formation is going on is known as an ossification center (Fig. 
 153) and the irregular anastomosing trabeculae of bone with the enclosed marrow 
 spaces constitute primary spongy bone. 
 
 From this time on, ossification gradually progresses toward each end of the 
 cartilage, and at the same time a special modification of the cartilage precedes 
 it. Nearest the ossification center the cartilage cell spaces become enlarged and 
 
 Cartilage cell spaces 
 (primary marrow space) 
 
 Disintegrating 
 cartilage cells 
 
 Cartilage cell 
 spaces 
 
 Blood vessel 
 
 m Trabecula 
 
 of cartilage 
 
 L 
 
 Osteogenetic tissue in 
 primary marrow space 
 
 FIG. 155.- From same section as Fig. 153; showing osteogenetic tissue pushing into the cartilage 
 and breaking it up into trabeculae. (Intracartilaginous ossification.) 
 
 arranged in rows and contain cartilage cells in various stages of disintegration. 
 Some of the septa break down, leaving larger, irregular spaces; the remaining 
 septa become calcified (Fig. 153). Passing away from the center of ossifica- 
 tion, there is less enlargement of the cell spaces and they have a tendency to be 
 arranged in rows transverse to the long axis of the cartilage; there is also a lesser 
 degree of calcification. The region of modified cartilage at each end of the 
 ossification center passes over gradually into ordinary hyalin cartilage and is 
 known as the calcification zone. It always precedes the formation of bone as 
 the latter process moves toward the end of the cartilage (Fig. 153). 
 
 Along with the type of ossification just described subperiosteal ossification 
 also occurs (Fig. 153). Beneath the periosteum (perichondrium) is a layer of 
 connective tissue the cells of which are transformed into osteoblasts. Thev 
 
THE CONNECTIVE TISSUES AND THE SKELETAL SYSTEM. 
 
 175 
 
 deposit layers of calcium salts on the surface of the cartilage in the same 
 manner as around the trabeculae inside the cartilage. 
 
 The transformation of the spongy bone into compact bone is peculiar 
 in that the former is dissolved and then replaced by new bone. This 
 dissolution is brought about by the action of the osteoclasts large mul- 
 tinuclear cells the origin of which is not known. By the process of dis- 
 solution the marrow spaces are increased in size and are known as Haver- 
 sian spaces. Within these spaces new bone is then deposited layer upon layer, 
 under the influence of the osteoblasts, until the Haversian spaces are reduced 
 to narrow channels, the Haversian canals. The layers of bone are the Haver- 
 sian lamella. The interstitial lamella in compact bone have two possible 
 origins. They may be the remnants of certain lamellae of the original spongy 
 
 Blood vessel 
 
 Bone 
 
 Cartilage 
 
 Bone cell 
 
 Cartilage cell 
 
 Cartilage cell space 
 
 FIG. 156. From same section as Fig. 153; showing bone deposited around one of the 
 trabeculae of cartilage. (Intracartilaginous ossification.) 
 
 bone which were not removed in the enlargement of the primary marrow spaces, 
 or they may be parts of early formed Haversian lamellae which were later more 
 or less replaced by other Haversian lamellae. 
 
 The fact should be emphasized that although it is convenient to describe 
 three types of bone formation, the three do not differ essentially from one 
 another. The similarity of intramembranous and subperiosteal ossification has 
 already been noted (p. 172). In both these types the bone is developed within 
 a membrane of embryonic connective tissue by a transformation of this tissue 
 into osteogenetic tissue and then of the latter into bone. The only way in 
 which intracartilaginous bone formation differs from the other two types is 
 that cartilage is first formed within the membrane in the same general shape as 
 the future bone. But it must be remembered that it is only in this cartilage that 
 bone is developed and not from it, the bone being produced by osteogenetic 
 
176 TEXT-BOOK OF EMBRYOLOGY. 
 
 tissue which in turn is derived from the embryonic connective tissue brought 
 into the cartilage by the periosteal bud. 
 
 GROWTH OF BONES. The way in which the cranial cavity enlarges has been 
 described on page 171. While the process of enlargement is going on, the 
 individual bones increase in size principally by the addition of new bone along 
 their edges. 
 
 Intracartilaginous bones grow both in diameter and in length. It has 
 already been stated that the primary spongy bone formed in cartilage is dis- 
 solved and that new bone is deposited under the periosteum. This naturally 
 brings about an enlargement of the primary marrow cavity and at the same 
 time an increase in the diameter of the bone as a whole. From this it is obvious 
 that the compact bone of the shaft of a long bone is of subperiosteal origin, the 
 intracartilaginous bone having been completely absorbed. 
 
 A. B 
 
 FIG. 157. Diagram representing growth in diameter of a long bone. 
 
 from Flourens. 
 
 The fact that the osseous tissue bordering the marrow cavity is absorbed and that new 
 bone is deposited under the periosteum can be quite clearly demonstrated. A young 
 growing animal is fed for a few weeks on madder, which colors all the bone formed during that 
 time a distinct red. If the animal is then killed and sections made of the long bones, the 
 outer part of the latter will appear a distinct red. Another growing animal is fed on madder 
 for a few weeks, then allowed to live a few weeks longer without madder. Then if it is 
 killed and sections made of the bones, the red bone is found to be covered with a layer of 
 uncolored bone which was deposited after the madder feeding had been stopped. If a 
 young growing animal is fed on madder for a time and then allowed to live long enough 
 without madder, the red bone will be found lining the marrow cavity. (See Fig. 157.) 
 
 Growth in length of the long bones takes place in a different manner. The 
 primary center of ossification is situated near the middle of the piece of cartilage, 
 and ossification proceeds in both directions toward the ends of the cartilage to 
 produce the diaphysis or shaft of the bone. In each end of the cartilage there 
 appears a secondary center from which ossification proceeds in all directions to 
 produce the epiphysis. Between the shaft and epiphysis a disk of cartilage 
 remains, and here, so long as the bone is growing, new cartilage continues to be 
 formed. At the same time new bone is being formed in the new cartilage, 
 
THE CONNECTIVE TISSUES AND THE SKELETAL SYSTEM. 
 
 177 
 
 principally in the part next the shaft. This produces an elongation of the 
 shaft, the two epiphyses being carried farther and farther apart, and conse- 
 quently a lengthening of the bone as a whole. When the bone reaches the 
 required length, the cartilage disk diminishes and finally is wholly replaced by 
 bone, being represented in the adult only by the epiphyseal line. (See Fig. 158.) 
 MARROW. The forerunner of marrow is the osteogenetic tissue in the pri- 
 mary marrow spaces, which in turn is derived from embryonic connective tissue 
 (Fig. 155). During the development of bone, great numbers of osteoblasts are 
 
 FIG. 158. Longitudinal section from head of femur of young dog. Photograph. 
 The head of the femur is shown in the upper part of the figure, the end of the shaft in the lower 
 part. Between the two the lighter line represents the cartilage between the primary center 
 of ossification (shaft) and the secondary center (epiphysis, head), and marks the site of the 
 epiphyseal line. The lighter portion covering the head represents the cartilage bordering 
 the joint cavity. 
 
 constantly being differentiated from the connective tissue cells and many of 
 these ultimately become bone cells. When development ceases, osteoblasts 
 cease to become differentiated. When dissolution of bone becomes neces- 
 sary, osteoclasts appear. Their origin is not known with certainty. One 
 view is that they represent several osteoblasts which have fused to form a 
 single, large multinucleated cell. Their relation to the myeloplaxes (giant 
 cells) in adult marrow is also a matter of doubt, though it is possible that 
 the polykaryocytes are their direct descendants. The myeloUasts, or pro- 
 genitors of the myelocytes, are approximately spherical cells, larger than white 
 
178 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 blood cells, mononuclear and with slightly basophilic cytoplasm. They 
 probably arise from mesenchymal cells or even from the elements of the 
 reticular tissue, and probably also constitute the cells from which not only 
 the myelocytes but also red and white blood cells are derived. In forming 
 the myelocyte series they acquire certain granules in the cytoplasm which 
 may be neutrophile, acidophile or basophile, giving the cell its distinguish- 
 ing character. The bone marrow in the adult is normally the only source 
 of erythrocytes and one of the sources of leucocytes. Further discussion 
 of these cells will be found on page 271. In young marrow there is little 
 or no fat present, but in later life many of the connective tissue cells are 
 transformed into fat cells (p.i68),so that these form the greater part of 
 the marrow. Such a process occurs most extensively in the shaft of the long 
 bones and gives rise to " yellow" marrow. In the heads of the long bones, 
 in the ribs, and in the short bones the marrow retains its earlier character 
 and is known as "red" marrow. 
 
 THE DEVELOPMENT OF THE SKELETAL SYSTEM. 
 The Axial Skeleton. 
 
 The Notochord. The notochord (chorda dorsalis) constitutes the 
 primitive axial skeleton of all Vertebrates, yet it differs from the other skeletal 
 elements in that it is a derivative of the entoderm. In man it is merely a tran- 
 sient structure and disappears early in foetal life, leaving but a slight trace of 
 itself in the intervertebral disks. In embryos of 2-3 mm. the cells of the 
 
 Mesoderm"" 
 
 Anlage of 
 notochord 
 
 Entoderm 
 
 FIG. 159. From transverse section of human embryo with 8 pairs of 
 primitive segments (2.69 mm.). Kollmann. 
 
 entoderm just ventral to the neural groove become slightly differentiated 
 (Fig. 159) and then form a groove with a ventral concavity. The groove closes 
 in, becomes constricted from the parent tissue (entoderm) and lies just ventral to 
 the neural tube, where it soon becomes surrounded by mesodermal tissue. This 
 structure is the notochord and constitutes a solid, cylindrical cord of cells 
 extending from a point just caudal to the hypophysis to the caudal extremity of 
 the embryonic body. In embryos of 17-20 mm. the mesodermal tissue around 
 the notochord becomes modified to form the chordal sheath. On account of its 
 position the notochord naturally becomes embedded in the developing vertebral 
 
THE CONNECTIVE TISSUES AND THE SKELETAL SYSTEM. 179 
 
 column, extending through the bodies of the vertebrae and the intervertebral 
 disks. The cells are at first of an epithelial nature (Fig. 159), but those within 
 the vertebral bodies become vacuolated and broken up into irregular, multinu- 
 clear masses which then disappear. The cord is thus first interrupted in the 
 vertebrae, leaving only the segments within the intervertebral disks. Later these 
 segments also undergo degenerative changes, but persist as the so-called pulpy 
 nuclei. 
 
 While the notochord is morphologically the forerunner of the axial skeleton, 
 and persists as a whole in Amphioxus, and in part in Fishes and Amphibia, in 
 the higher forms it is almost exclusively an embryonic structure with little or no 
 functional significance. It differs in origin from the true skeletal elements and 
 becomes involved with them only to disappear as they develop. 
 
 Intersegmental 
 
 artery 
 
 Notochord 
 
 i 
 
 Parts of two 
 adjacent sclerotomes 
 
 FIG. 160. Five myotomes and sclerotomes from sagittal section of human embryo of 5 mm. Bardeen. 
 
 Each sclerotome is differentiated into a looser cephalic part and a denser caudal part, the two 
 
 being separated by a cleft (fissure of von Ebner). 
 
 The Vertebrae. The changes which occur in the ventro-medial parts of the 
 primitive segments to form the sclerotomes have already been described. At 
 the same time it w r as stated that the vertebrae, with the other types of connective 
 tissue around them, were derived from the mesenchymal tissue of the sclerotomes 
 (p. 163; see also Fig. 142). The segmentally arranged masses forming the 
 sclerotomes are separated by looser tissue in which the intersegmental arteries 
 develop. The arteries mark the boundaries between the sclerotomes (Fig. 160). 
 About the third week of development the caudal part of each sclerotome con- 
 denses to form a more compact mass of tissue, and a little later becomes 
 separated from the cephalic part by a small cleft (Fig. 161). From the denser 
 caudal part a secondary mass of tissue grows medially and meets and fuses with 
 its fellow of the opposite side, thus enclosing the notochord. The medial mass 
 
180 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 thus formed may be considered as the anlage of the body of a vertebra. Another 
 secondary mass also grows dorsally between the myotome and the spinal cord, 
 forming the anlage of the vertebral arch. A third mass grows ventro-laterally to 
 form the costal process (Figs. 162 and 163). The looser tissue of the cephalic 
 part of each sclerotome also sends an extension medially to surround the 
 notochord, and fills up the intervals between the succeeding denser (caudal) 
 parts. The looser part also forms a sort of membrane between the succeeding 
 vertebral arches. The tissue between the denser caudal part and the looser 
 cephalic part of each sclerotome is destined to give rise to an intervertebral 
 Jibrocartilage. While the denser tissue forming the caudal part of each sclero- 
 
 Dermis 
 
 Myotome 
 
 Notochord 
 
 Cleft 
 
 Intersegmental artery 
 
 Perichordal sheath 
 Intervertebral disk 
 Interdiscal membrane 
 
 FIG. 161. Six myotomes and sclerotomes from sagittal section of human embryo of 6 mm. 
 Bardeen. Compare with Fig. 160. 
 
 tome probably gives rise to the greater part of a vertebra, the looser tissue of the 
 cephalic part is also involved in the formation of the cartilaginous body, as will 
 be noted again in the following paragraph. The peculiar feature of the process 
 is that the denser caudal part of a sclerotome becomes associated with the looser 
 cephalic part of the next succeeding sclerotome, so that each vertebra is derived 
 from parts of two adjacent sclerotomes and not from a single sclerotome. This 
 naturally brings about an alternation of vertebra and myotomes (Fig. 161). 
 
 So far the anlagen of the vertebrae are in the so-called blastemal stage. 
 
 Following the blastemal stage and beginning in human embryos of about 15 
 mm., comes the cartilaginous stage in which the mesenchymal anlagen of the 
 vertebras are converted into embryonic hyalin cartilage. In the body of each 
 vertebra a center of chondrification appears in the looser tissue of the caudal 
 
THE CONNECTIVE TISSUES AND THE SKELETAL SYSTEM. 
 
 181 
 
 part and gradually enlarges and involves the denser cephalic part. It is to be 
 noted that the denser tissue of the cephalic part of a vertebral body corresponds 
 to the caudal part of a sclerotome. Two chondrification centers appear, one on 
 
 Costal process 
 
 Aorta 
 
 Stomach 
 
 Arch of 
 vertebra 
 
 Notochord 
 
 Body of 
 vertebra 
 
 Mesonephros 
 
 Liver 
 
 FIG. 162. Transverse section (dorsal part) of pig embryo of 14 mm. Photograph. 
 
 each side of the medial line, but the two soon fuse around the notochord to 
 form a single center. In addition to the center in the body of the vertebra, one 
 also appears in each half of the vertebral arch, and one in each costal process 
 
 Interdorsal membrane 
 
 Notochord 
 
 Bodies of 
 vertebrae 
 
 Costal process 
 FIG. 163. Models of three vertebrae in the blastemal stage; from an embryo of n mm. Bardeen. 
 
 (Fig. 164). All these centers then enlarge and unite to form a single mass of 
 cartilage which corresponds quite accurately in shape to the future bony 
 vertebra. Processes then grow out from the vertebral arch. These represent 
 
182 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 the transverse and articular processes (Fig. 165). Each half of a vertebral 
 arch meets its fellow of the opposite side dorsal to the spinal cord, and from 
 the point of meeting the spinous process grows out. The costal processes do 
 
 Costal process 
 (rib) 
 
 Body of 
 vertebra 
 
 Costal process 
 (rib) 
 
 Aorta 
 
 Pleural cavity Liver (Esophagus Lung 
 
 FIG. 164. Transverse section (dorsal part) of pig embryo of 35 mm. Photograph. 
 
 not retain their connection with the body of the vertebra, but break away 
 and become the rib cartilages, as will be noted again in connection with the 
 development of the ribs. 
 
 Following the cartilaginous stage is the stage of ossification in which the 
 
 Arch of vertebra 
 Post, articular 
 process 
 
 Transverse process 
 
 Anterior articular process 
 
 FIG. 165. Models of the 6th, 7th and 8th thoracic vertebrae of an embryo of 33 mm. 
 
 (dorsal view). Bardeen. 
 On the right the cartilage is shown, on the left the surrounding fibrous tissue. 
 
 vertebrae become ossified and acquire the adult condition. Ossification begins 
 during the third month of fcetal life and extends over a long period, even up to 
 the age of twenty-five years. A single center of ossification appears in the body 
 
THE CONNECTIVE TISSUES AND THE SKELETAL SYSTEM. 
 
 183 
 
 of each vertebra, and following this a center in each half of the vertebral arch 
 (Fig. 1 66). Osseous tissue then gradually replaces the cartilage. The two 
 halves of an arch fuse dorsal to the spinal cord during the first year of post- 
 natal life, thus completing the bony arch. The arch fuses with the body of the 
 
 Med. ossif. cents 
 
 FIG. 166. Thoracic vertebra and ribs of human embryo of 55 mm. (middle of 
 
 3rd month). Kollmann's A tlas. 
 Cartilage indicated by stippled areas, ossification centers by irregular black lines. 
 
 vertebra between the third and eighth years. Thus it is seen that the process of 
 ossification is a slow one, and this is even more striking when one considers the 
 formation of the secondary centers. For at about the age of puberty a secondary 
 center appears in each of the cartilages that cover the ends of the vertebrae, pro- 
 
 Spinous process 
 Transverse process 
 Articular process 
 
 Body of vertebra 
 
 Upper epiphyseal 
 plate 
 
 FIG. 167. Lumbar vertebra (lateral view) showing secondary centers of ossification. Sappey. 
 
 ducing disks of bone the epiphyses. A secondary center also appears in the 
 cartilage on the tip of each spinous process and transverse process, and in the 
 lumbar vertebrae one appears also on the tip of each articular process (Fig. 167). 
 The epiphyses unite with the vertebrae any time between sixteen and twenty- 
 
184 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 five years. About the twenty-fifth year the sacral vertebrae unite to form a 
 single mass of bone, and a similar union also takes place between the more or 
 less rudimentary coccygeal vertebrae. 
 
 While the general plan of development is practically the same in all the 
 vertebrae, there are a few noteworthy modifications. The greatest modification 
 is in the atlas and epistropheus (axis). The entire atlas is formed from the 
 denser caudal part of a sclerotome. The lateral mass and the posterior (dorsal) 
 arch represent the vertebral arch. The anterior (ventral) arch represents the 
 hypochordal bar, a plate of cartilage which develops in all vertebrae ventral to 
 the notochord but disappears in all except the atlas. A body also develops 
 but instead of forming part of the atlas it unites with the body of the epistro- 
 pheus to form the dens (odontoid process) of the latter. 
 
 Clavicle 
 
 Suprasternal cartilage 
 
 Sternal bar 
 
 7th rib 
 
 FIG. 168. Ventral view of developing sternum of human embryo of 30 mm. 
 (beginning of 3rd month). Ruge, Kollmann's Atlas. 
 
 The various ligaments of the vertebral column are derived from the embry- 
 onic connective tissue surrounding the vertebrae. The embryonic connective 
 tissue in the clefts separating the developing vertebrae is transformed into the 
 intervertebral fibrocartilages. 
 
 The Ribs. It has been stated in a previous paragraph that the costal proc- 
 esses arise as outgrowths from the denser caudal parts of the sclero tomes; that 
 they grow in a ventro-lateral direction and consequently are at first connected 
 with and are parts of the bodies of the vertebrae (Figs. 162 and 165). These 
 costal processes are the anlagen of the ribs, and they continue to grow ventrally 
 until they practically encircle the body, the ventral ends of a number of them 
 fusing in the medial line to form the sternum. The primary junctions between 
 the costal processes and vertebrae are dissolved, and the embryonic connective 
 tissue in this region gives rise to the costo-vertebral ligaments. The dissolu- 
 tion of the junctions leaves the ribs simply articulating with the vertebrae. 
 
THE CONNECTIVE TISSUES AND THE SKELETAL SYSTEM. 
 
 185 
 
 A chondrification center appears in each costal process, shortly after that in 
 the body of the vertebra, and from this point the formation of cartilage 
 gradually extends throughout the entire rib. 
 
 Ossification begins during the third month at a center which is situated near 
 the angle of the rib (Fig. 166). At the age of eight to fourteen years a second- 
 ary center appears in each capitulum and tuber culum and subsequently fuses 
 with the rest of the rib at the age of fourteen to twenty-five years. As the 
 tuberculum develops, the transverse process of the corresponding vertebra 
 grows ventrally and caudally to meet it and form the articulation. 
 
 The ribs reach the highest degree of development in the thoracic region 
 where one develops on each side, corresponding to each vertebra. The first 
 seven or eight thoracic ribs extend almost to the mid- 
 ventral line and are attached to the sternum; the last four 
 or five become successively shorter and are only indirectly 
 or not at all attached to the sternum. In the cervical 
 region the ribs do not reach a high degree of development. 
 Their tips simply fuse with the transverse processes of the 
 vertebras and their heads with the bodies of the vertebrae, 
 leaving a space the foramen transversarium through 
 which the vertebral vessels pass. The seventh cervical rib 
 may, however, reach a fairly high degree of development. 
 In the lumbar region also the ribs are reduced to small 
 pieces of bone which are firmly united with the transverse 
 processes and form the accessory processes. In the sacral 
 region the rudimentary ribs unite to form the lateral part 
 (pars lateralis) of the sacral bone. After the blastemal 
 stage there are no indications of ribs in the coccygeal region. 
 In the blastemal stage, however, there is a small bit of tissue FIG. 169. Sternum of 
 which probably represents the anlage of a rib, but soon 
 fuses with the transverse process. 
 
 The Sternum. The sternum is formed by the fusion 
 of the ventral ends of the first eight or nine thoracic ribs. 
 A longitudinal bar is first formed on each side of the medial 
 line by the fusion of the ventral ends of the ribs on each side; then the two bars 
 unite in the medial line to form a single piece of cartilage (Figs. 168 and 169). 
 Subsequently the last one or two ribs become separated from the sternum, 
 leaving only seven or eight connected with it. At the cephalic end of the 
 sternum two separate pieces of cartilage episternal cartilages appear, with 
 which the clavicles articulate (Fig. 168). These usually unite with the longi- 
 tudinal bar to form a part of the manubrium, but they may remain separate 
 and ossify to form the supr asternal bones (ossa suprasternalia). 
 
 old child, 
 centers of 
 ossification. Seven 
 ribs are attached on 
 the right side, 8 on 
 the left. Markcnvski, 
 Kollmann's Atlas. 
 
186 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 Ossification begins in the sternum about the end of the fifth month of foetal 
 life. In each of the two cephalic segments a single center appears; caudal to the 
 second segment a series of paired centers appears, and later the centers of each 
 pair fuse into a single center (Fig. 169). The paired centers possibly represent 
 epiphyses of the ribs. Sometimes, however, the centers appear as a single 
 series, that is, with no indication of a paired character. The ossification 
 of the most cephalic segment, along with the episternal cartilages, produces the 
 manubrium sterni. Ossification of the following six or seven segments and their 
 union produce the corpus sterni. The bars formed from the most caudal ribs 
 (excluding the false ribs) form the xyphoid process. This process remains car- 
 
 Olfactory organ 
 Hypophysis 
 Visual organ 
 
 Prechordal plate 
 
 Auditory organ 
 
 Parachordal plate 
 
 Notochord 
 
 Nasal septum 
 
 Olfactory organ 
 Hypophysis 
 Visual organ 
 
 Prechordal plate 
 Auditory organ 
 
 Basal (parachordal) 
 plate 
 
 Notochord 
 
 FIG. 170. FIG. 171. 
 
 FIG. 170. Diagram of first stage in the development of the cartilaginous 
 
 primordial cranium. Wiedersheim. 
 FIG. 171. Diagram of later stage of same. Wiedersheim. 
 
 tilaginous for a long period, and may be single, perforated, or bifurcated, de- 
 pending upon the degree of fusion between the two primary bars. 
 
 The Head Skeleton. Topographically the skeleton of the head appears 
 as the cephalic part of the axial skeleton. Structurally it is decidedly different, 
 for it is adapted to different conditions. The neural tube here becomes differ- 
 entiated into the brain with its many and dissimilar parts. In connection with 
 the brain the complicated sense organs (nose, eye and ear) arise. A part of 
 the alimentary tract and portions of the visceral arches are also inclosed 
 within the head. The head skeleton is specially modified to accommodate 
 these highly developed organs, and becomes extremely complicated. In 
 general the skeleton in any part of the body adapts itself to the other structures 
 and not the other structures to the skeleton. 
 
 The anlage of the skull is a mass of embryonic connective tissue which sur- 
 
THE CONNECTIVE TISSUES AND THE SKELETAL SYSTEM. 
 
 187 
 
 rounds the cephalic end of the notochord, extends from there into the nasal 
 region and also extends around the sides and dorsal part of the neural tube 
 (brain). Unlike the anlage of the vertebral column, the anlage of the skull 
 shows no distinct division into primitive segments. The only indications of a 
 segmental character are referred to in a succeeding paragraph (small print, 
 p. 189). 
 
 The next step in the development of the skull is the appearance of cartilage 
 in certain regions of the embryonic connective tissue. On account of the com- 
 plicated arrangement of the cartilage in the human skull, it is best to consider 
 
 Palatoquadrate 
 
 Palatoquadrate 
 Meckel's cartilage 
 
 Palatoquadrate 
 Hypophysis 
 
 Nasal fossa 
 Preorbital process 
 
 Roof of skull 
 Marginal bar 
 
 Prechordal plate 
 Prootic incisure 
 Jugular foramen 
 
 } Foramina (VII Nerve) 
 
 Notochord 
 >Otic (auditory) capsule 
 
 Synotic tectum 
 
 FIG. 172. Primordial cranium of Salmo salar (salmon) embryo of 25 mm. Dorsal view. Gaupp. 
 Compare with Fig. 171 and note further elaboration of parts surrounding the sense organs. 
 
 first its more simple arrangement in the lower Vertebrates. In these there ap- 
 pear in the embryonic connective tissue around the cephalic end of the notochord 
 two bilaterally symmetrical pieces of cartilage, which extend as far as the 
 hypophysis. Then two other bilaterally symmetrical pieces appear, extending 
 from the hypophysis to the nasal region. Subsequently all these pieces fuse 
 into a single mass which extends from the cephalic end of the vertebral column 
 to the tip of the nose, enclosing the end of the notochord and, to a certain ex- 
 tent, the ear, eye and olfactory apparatus. There is left, however, an opening 
 for the hypophysis. From this mass of cartilage, chondrification extends into 
 the embryonic connective tissue along the sides and roof of the cranial 
 
188 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 cavity, so that the brain and sense organs are practically enclosed. To this 
 capsule the term cartilaginous primordial cranium has been applied. (See 
 Figs. 170, 171, 172.) 
 
 In the higher Vertebrates, chondrification is limited to the basal region of the 
 skull, while the side walls and roof are formed later by intramembranous bone. 
 
 Meckel's cartilage 
 Malleus 
 
 Incus 
 
 Int. acoustic pore 
 Jugular foramen 
 
 Subarcuate fossa 
 
 Ala magna (sphenoid) 
 Optic foramen 
 
 Ala parva (sphenoid) 
 
 Sella turcica 
 Dorsum sellae 
 
 Foramina 
 (VII Nerve) 
 
 Auditory 
 capsule 
 
 Foramen 
 
 Foramen (XII Nerve) 
 
 Large occipital foramen Occipital 
 
 (foramen magnum) (synotic tectum) 
 
 FIG. 173. Dorsal view of primordial cranium of human embryo of 80 mm. 
 
 (3rd month). Gaupp. Hertwig. 
 
 The membrane bones of the roof of the skull have been removed. Through the large occipital 
 foramen can be seen the first three cervical vertebrae. 
 
 In the human embryo chondrification occurs first in the occipital and sphenoidal 
 regions, and then gradually extends into the nasal (ethmoidal) region. A little 
 later it spreads somewhat dorsally in the occipital and sphenoidal regions to form 
 part of the squamous portion of the occipital and the wings of the sphenoid. At 
 the same time cartilage develops in the embryonic connective tissue surround- 
 
THE CONNECTIVE TISSUES AND THE SKELETAL SYSTEM. 
 
 189 
 
 ing the internal ear to form the periotic capsule which subsequently unites with 
 the occipital and sphenoidal cartilages. The pieces of cartilage thus formed con- 
 stitute the chondrocranium. 
 
 In connection with the development of the caudal part of the occipital cartilage there is 
 an interesting feature which is at least indicative of a segmental character. In some of the 
 lower Mammals there are four fairly distinct condensations of embryonic connective tissue 
 just cranial to the first cervical vertebra, corresponding to the first cervical nerve and the 
 three roots of the hypoglossal. These condensations bear a general resemblance to the 
 primitive segments and indicate the existence of four vertebrae which are later taken up into 
 the chondrocranium. In the human embryo the condensations are less distinct, but the 
 existence of a first cervical and a three-rooted hypoglossal nerve in this region suggests an 
 original segmental character. If this is true, then the base of the human skull is formed 
 from the unsegmented chondrocranium plus four vertebrae which become incorporated in 
 the occipital region. 
 
 Optic foramen 
 
 Ala magna (sphenoid) 
 
 Ala parva (sphenoid) 
 
 Vomer 
 Palate bone 
 
 Mandible 
 
 Meckel's cartilage 
 
 Cricoid cartilage 
 
 \ Styloid process 
 Cochlear fenestra 
 
 Foramen (XII Nerve) 
 
 Thyreoid cartilage 
 
 FIG. 174. Lateral view of primordial cranium of human embryo of 80 mm. 
 
 (3rd month). Gaupp, Hert-wig. 
 
 The membrane bones of the roof of the skull have been removed. Compare with FIG. 173. 
 maxilla, vomer, palate, and mandible are membrane bones. 
 
 The 
 
 In addition to the chondrocranium, other cartilaginous elements enter into 
 the formation of the skull, all of which are derived from the visceral arches. 
 Not all the arches, however, produce cartilage; for in the maxillary process of 
 the first arch, which forms the upper boundary of the mouth, cartilage does not 
 appear, and the bones which later develop in it are of the membranous type. 
 The mandibular process of the first arch produces a rod of cartilage Meckel's 
 cartilage. This gives rise, at its proximal end, to a part of the auditory ossicles, 
 but the cartilage in the jaw proper soon wholly or almost wholly disappears. 
 The cartilage of the second arch becomes connected with the skull in the region 
 
190 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 of the periotic capsule. The cartilages of the other three arches are only 
 indirectly connected with the skull and will be considered later. 
 
 Figs. 1 73 and 174 show the condition of the chondrocranium in a human 
 embryo of 80 mm. (third month) . Although at first glance it seems exceedingly 
 complicated, a careful study and comparison of the various parts will aid the 
 student in his comprehension of the cartilaginous foundation upon which the 
 skull is built. 
 
 OSSIFICATION OF THE CHONDROCRANIUM. 
 
 In the human foetus ossification begins in the occipital region during the 
 third month. Four centers appear which correspond to the four parts of the 
 adult occipital bone (Fig. 175). (i) An unpaired center situated ventral to the 
 foramen magnum. From this center ossification proceeds in all directions to 
 
 Interparietal 
 (of lower forms) 
 
 Squamous part 
 ' (intramemb.) 
 
 Squamous 
 part 
 
 Kerkringius' bone 
 
 Squamous part 
 (intracartilag.) 
 
 Lateral part 
 
 Basilar part 
 
 FIG. 175. Occipital bone of human embryo of 21.5 cm. Kollmann's Atlas. 
 
 form the pars basilaris (basioccipital). (2 and 3) Two lateral centers, one 
 on each side. From these, ossification proceeds to produce the partes laterales 
 (exoccipital) which bear the condyles. (4) A center dorsal to the foramen, 
 magnum. This produces the pars squamosa (supraoccipital) as far as the supe- 
 rior nuchal line. Beyond this line the pars squamosa is of intramembranous 
 origin. (See p. 192.) At birth the four parts are still separated by plates of 
 cartilage. During the first or second year after birth the partes laterales 
 unite with the pars squamosa, and about the seventh year the pars basilaris 
 unites with the rest of the bone. 
 
THE CONNECTIVE TISSUES AND THE SKELETAL SYSTEM. 191 
 
 In the sphenoidal region ossification begins at a number of centers which, 
 as in the occipital region, correspond generally to the parts of the adult sphenoid 
 bone (Fig. 176). (i and 2) About the ninth week an ossification center 
 appears on each side in the cartilage which corresponds to the ala magna 
 (alisphenoid). (3 and 4) About the twelfth week a center appears on each 
 side which corresponds to the ala parva (orbitosphenoid). (5 and 6) A 
 short time after this a center appears on each side of the medial line in the 
 basal part of the cartilage, and the two centers subsequently fuse to produce the 
 corpus (basisphenoid). (7 and 8) Lateral to each basal center, another center 
 appears which represents the beginning of the lingula. (9 and 10) Finally 
 two centers appear in the basal part of the cartilage, in front of the other 
 basal centers, and then fuse to form the presphenoid. As in the case of the oc- 
 cipital bone, not all of the adult sphenoid is of intracartilaginous origin; for the 
 
 Ala parva- 
 
 Ala magna 
 
 Lingula 
 
 corpus 
 ' (basisphenoid) 
 
 FIG. 176. Sphenoid bone of embryo of 3^-4 months. Sappey. 
 The parts that are still cartilaginous are represented in black. 
 
 upper anterior angle of each ala magna is of intramembranous origin, as are also 
 the medial and lateral laminae of the pterygoid process. The pterygoid hamulus, 
 however, is formed by the ossification of a small piece of cartilage which de- 
 velops on the tip of the medial lamina. The fusion of these various parts oc- 
 curs at different times. The lateral pterygoid lamina unites with the alisphe- 
 noid before the sixth month of foetal life; about the sixth month the lingula fuses 
 with the basisphenoid, and the presphenoid with the orbitosphenoid. The 
 alisphenoid and medial pterygoid lamina fuse with the rest of the bone during 
 the first year after birth. The union of the basisphenoid and basioccipital 
 usually occurs when the growth of the individual ceases, though the two bones 
 may remain separate throughout life. 
 
 In the region of the periotic capsule, several centers of ossification appear in 
 the cartilage during the fifth month. During the sixth month these centers 
 unite to form a single center which then gradually increases to form the pars 
 petrosa and pars mastoidea of the adult temporal bone. The mastoid process is 
 
192 TEXT-BOOK OF EMBRYOLOGY. 
 
 formed after birth by an evagination from the pars petrosa, and is lined by an 
 evaginated portion of the mucosa of the middle ear. The other parts of the 
 temporal bone are of intramembranous origin, except the styloid process which 
 represents the proximal end of the second branchial arch. 
 
 In the ethmoidal region, conditions become more complicated on account of 
 the peculiarities of the nasal cavities, and on account of the fact that the cartilage 
 is never entirely replaced by bone, and that "membrane" bones also enter into 
 more intimate relations with the "cartilage" bones. The ethmoidal cartilage 
 at first consists of a medial mass, which extends from the presphenoid region to 
 the end of the nasal process, and of a lateral mass on each side, which is situated 
 lateral to the nasal pit (Fig. 1 74) . Ossification in the lateral mass on each side 
 produces the ethmoidal labyrinth (lateral mass of ethmoid). It is perhaps not 
 quite correct to say that ossification produces the ethmoidal labyrinth, for at 
 first there is only a mass of spongy bone with no indication of the honey-combed 
 structure characteristic of the adult. The latter condition is produced by a 
 certain amount of dissolution of the bone and the growth of the nasal mucosa 
 into the cavities so formed. By the same process of dissolution and ingrowth of 
 nasal mucosa the superior, middle and inferior concha (turbinated bones) are 
 formed. The medial mass of cartilage begins to ossify after birth and then only 
 in its upper (superior) edge. It forms the lamina perpendicularis and crista 
 galli and extends into the nose as the nasal septum. The lower (inferior) edge 
 remains as cartilage until the vomer, which is a membrane bone (p. 194), 
 develops, after which it is partly dissolved. The lamina cribrosa (cribriform 
 plate) is formed by bony trabeculae which extend across between the medial 
 mass and the lateral masses and surround the bundles of fibers of the olfactory 
 nerve. 
 
 MEMBRANE BONES OF THE SKULL. 
 
 Under this head we shall consider only those bones which develop apart 
 from the visceral arches, those which involve the arches being considered later. 
 It has been seen that by far the greater parts of the bones forming the base of the 
 skull are of intracartilaginous origin. On the other hand, those forming the 
 sides and roof of the skull are largely of intramembranous origin. In the case 
 of the occipital bone, two centers of ossification appear in the membrane dorsal 
 to the supraoccipital, and the bone so formed begins to unite with the supra- 
 occipital during the third month of fcetal life. At birth the union is usually 
 complete, though for a time an open suture may persist on each side. The bone 
 derived from the two centers forms that part of the occipital squama which is 
 situated above the superior nuchal line; the part below the line is of intracarti- 
 laginous origin (p. 190). The adult occipital is thus a composite bone, partly 
 of intramembranous, partly of intracartilaginous origin. 
 
THE CONNECTIVE TISSUES AND THE SKELETAL SYSTEM. 
 
 193 
 
 The temporal is also a composite bone, the petrous and mastoid parts 
 and the styloid process being of intracartilaginous origin, while the temporal 
 squama and the tympanic part- are of intramembranous origin. During the 
 eighth week of foetal life a center of ossification appears in the membrane in the 
 temporal region, and the bone formed from this center subsequently unites 
 with the petrous part and becomes the temporal squama. Another center ap- 
 pears in the membrane to the outer side of the periotic capsule and produces a 
 ring of bone around the external auditory meatus, which fuses with the petrous 
 
 Parietal 
 
 Occipital 
 
 fontanelle 
 
 Occipital -7 
 
 Mastoid - 
 fontanelle 
 
 Occipital 
 
 Petrous 
 
 Occipital 
 
 Tympanic 
 
 Styloid process 
 
 Stylohyoid lig. 
 
 Hyoid (greater horn) 
 
 Sphenoidal 
 fontanelle 
 
 Cricoid 
 
 Zygoma tic 
 Maxilla 
 
 Mandible 
 
 Meckel's cartilage 
 Hyoid (lesser horn) 
 
 Thyreoid 
 
 FIG. 177. Diagram of skull of new-born child. Combined from McMnrrich and Kollmann. 
 White areas represent bones of intramembranous origin: dotted areas represent bones (not derived 
 from branchial arches) of intracartilaginous origin; black areas represent derivatives of 
 branchial arches. 
 
 part and forms the tympanic part of the adult bone. It gives attachment at its 
 inner border to the tympanic membrane. While the union of the different 
 parts begins during foetal life, it is usually completed after birth. 
 
 The sphenoid bone is also composed of parts which have different 
 origins. The body, small wings and large wings are of intracartilaginous 
 origin, the pterygoid process of intramembranous origin. About the eighth 
 week of development a center of ossification appears in the mesenchyme in the 
 lateral wall of the posterior part of the nasal cavity and gives rise to the medial 
 pterygoid lamina. On the tip of the latter a small piece of cartilage appears in 
 
194 TEXT-BOOK OF EMBRYOLOGY. 
 
 which ossification later takes place to form the pterygoid hamulus (p. 191). 
 The lateral pterygoid lamina is also of intramembranous origin and fuses with 
 the medial lamina, the two laminae forming the pterygoid process which subse- 
 quently unites with the body of the sphenoid. (See Fig. 176.) 
 
 In the ethmoidal region, only the vomer is of intramembranous origin. An 
 ossification center appears in the embryonic connective tissue on each side of 
 the perpendicular plate (lamina perpendicularis) and these two centers produce 
 two thin plates of bone which unite at their lower borders and invest the lower 
 part of the perpendicular plate. The portion of the latter thus invested 
 undergoes resorption. 
 
 The frontal and parietal bones are purely of intramembranous origin. About 
 the eighth week two centers of ossification, one on each side, appear for the 
 frontal. The bones produced by these centers unite in the medial line to form 
 the single adult bone. In the event of an incomplete union an open suture 
 remains the metopic suture. A single center of ossification appears for each 
 parietal bone at about the same time as those for the frontal. The union of 
 the bones which form the roof and the greater part of the sides of the skull does 
 not occur till after birth. The spaces between them constitute the sutures and 
 fontanelles so obvious in new-born children (Fig. 177). 
 
 A single center of ossification appears in the embryonic connective tissue 
 for each zygomatic, lachrymal and nasal bone, all of which are of intramem- 
 branous origin. 
 
 BONES DERIVED FROM THE BRANCHIAL ARCHES. 
 
 The first branchial arch becomes divided into two portions. One of these, 
 the maxillary process, is destined to give rise to the upper jaw and much of the 
 upper lip and face region. The other, the mandibular process, is destined to 
 give rise to the lower jaw, the lower lip and chin region, and two of the auditory 
 ossicles. The angle between the two processes corresponds to the angle of the 
 mouth, and the cavity enclosed by the processes is the forerunner of the mouth 
 and nasal cavities. (See Fig. 134, also p. 147.) So far as the skeletal elements 
 are concerned, cartilage develops only in the mandibular process where it 
 forms a slender bar or rod known as MeckeVs cartilage. Only a small part of 
 this becomes ossified, the greater portion of the mandible being of intramem- 
 branous origin. No cartilage develops in the maxillary process. This 
 probably indicates a condensation of development in man and the higher 
 animals, for among the lower animals cartilage precedes the bone. In man the 
 maxilla and palate bone also are of intramembranous origin. 
 
 The palate bone develops from a single center of ossification which appears 
 at the side of the nasal cavity in embryos of about 18 mm. This center 
 
THE CONNECTIVE TISSUES AND THE SKELETAL SYSTEM. 195 
 
 represents the perpendicular part, the horizontal part appearing in embryos of 
 about 24 mm. as an outgrowth from the perpendicular and not as a separate 
 center of ossification. The orbital and sphenoidal processes also represent out- 
 growths from the primary center and appear much later. 
 
 Opinions regarding the development of the maxilla are at variance. One 
 view is that it arises from five centers of ossification. One of these centers gives 
 rise to that part of the alveolar border which bears the molar and premolar 
 teeth; a second center forms the nasal process and that part of the alveolar bor- 
 der which bears the canine tooth; a third produces the part which bears the 
 incisor teeth; and the two remaining centers give rise to the rest of the bone. 
 All these parts effect a firm union at an early stage, with the exception of the 
 part bearing the incisor teeth which remains more or less distinct as the incisive 
 bane (premaxilla, intermaxilla) . Another view arising from recent work on 
 
 Incisive bone Upper lip 
 
 (intermaxillary) 
 
 Primitive choan* ^Kdfl "" Lip 8roove 
 
 Cut surface Palatine processes 
 
 FIG. 178. Head of human embryo of 7 weeks. His. 
 Ventral aspect of upper jaw region. Lower jaw and tongue have been removed. 
 
 human embryos is that there are primarily only two ossification centers; one of 
 these gives rise to the incisive bone, the other to the rest of the maxilla (Mall). 
 These centers appear at the end of the sixth week (embryos of 18 mm.). 
 
 A very important feature in the development of the maxilla is its agency in 
 separating the nasal cavity from the mouth cavity. The palatine process of the 
 bone grows medially and meets and fuses with its fellow of the opposite side in 
 the medial line, the two processes together thus constituting about the an- 
 terior three-fourths of the bony part of the hard palate. It should be observed, 
 however, that the palatine processes do not meet at their anterior borders, for 
 the incisive bone is insinuated between them (see Figs. 178, 179). 
 
196 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 The incisive bone is probably not derived from the maxillary process of the first visceral 
 arch, but from the fronto-nasal process. The question thus arises as to whether it is derived 
 from both the middle and lateral nasal processes or only from the middle. According to 
 Kolliker's view, the lateral nasal process takes no part in the formation of the incisive bone. 
 It is derived from the middle process, hence genetically it is a single bone on each side. 
 According to Albrecht's view the incisive bone is genetically composed of two parts, one 
 derived from the lateral, the other from the middle nasal process. While the matter is not 
 one of great importance merely from the standpoint of development, it has an important 
 bearing on the question of certain congenital malformations, e. g., hare lip, and will be 
 discussed further under that head (p. 212). 
 
 In the mandibular process of the first visceral arch, the mandible develops as 
 a bone which is partly of intramembranous and partly of intracartilaginous 
 origin. In the first place a rod of cartilage, known as Meckel's cartilage, 
 forms the core of the mandibular process and extends from the distal end of the 
 process to the temporal region of the skull, where it passes between the tympanic 
 
 Medial line 
 Canine alveolus 
 
 Molar alveolus 
 
 Incisive bone 
 
 Incisive suture 
 
 Palatine process 
 
 Palate bone 
 (horizontal part) 
 
 FIG. 179. Ventral aspect of hard palate of human embryo of 80 mm. Kollmann's Atlas. 
 
 bone and the periotic capsule and ends in the tympanic cavity of the ear (Fig. 
 174). During the sixth week of foetal life, intramembranous bone begins to 
 develop in the mandibular process. In the region of the body of the mandible 
 the bone encloses the cartilage, but in the region of the ramus and coronoid 
 process the cartilage lies to the inner side of the bone. Development is further 
 complicated by the appearance of cartilage in the region of the middle incisor 
 teeth and on the coronoid and condyloid processes. These pieces of cartilage 
 form independently of Meckel's cartilage and subsequently are replaced by the 
 bone which constitutes the corresponding parts of the mandible. The part of 
 Meckel's cartilage enclosed in the bone disappears; the part to the inner side of 
 the ramus is transformed into the sphenomandibular ligament. (See Fig. 180.) 
 In each half of the second branchial arch a rod of cartilage develops, which 
 extends from the ventro-medial line to the region of the periotic capsule. The 
 
THE CONNECTIVE TISSUES AND THE SKELETAL SYSTEM. 197 
 
 proximal end of this rod is then replaced by bone which fuses with the temporal 
 bone and forms the styloid process. The distal (ventral) end is replaced by 
 bone which forms the lesser horn of the hyoid bone. Between the styloid proc- 
 ess and the lesser horn, the cartilage is transformed into the stylohyoid liga- 
 ment (see Figs. 177 and 180). 
 
 In each half of the third branchial arch a piece of cartilage develops and 
 subsequently is replaced by bone to form the greater horn of the hyoid bone. 
 The two horns become connected at their ventral ends by the body of the hyoid 
 bone which is also a derivative of the third arch. Later the lesser horn fuses 
 with the greater horn to bring about the adult condition (Fig. 180). 
 
 In the ventral parts of the fourth and fifth arches pieces of cartilage develop 
 
 Incus Malleus 
 
 ^^^^m^^^^^^^ 
 
 Tympanic ring 
 Stylohyoid lig. 
 
 Cricoid cartilage 
 
 Thyreoid cartilage | Meckel's cartilage 
 
 Hyoid cartilage (greater horn) 
 
 FIG. 180. Lateral dissection of head of human foetus, showing derivatives of branchial 
 arches in natural position. Kollmann's Atlas. 
 
 and form the skeletal elements of the larynx. A more detailed account of these 
 will be found under the head of the larynx (p. 361). 
 
 The auditory ossicles are also derived largely from the branchial arches, the 
 incus and malleus being derived from the proximal end of Meckel's cartilage (first 
 arch) , the stapes having a double origin from the second arch and the embryonic 
 connective tissue surrounding the periotic capsule. But since they form inte- 
 gral parts of the organ of hearing, a discussion of their formation is best in- 
 cluded in the development of the ear (p. 589). 
 
 The accompanying table indicates the types of development in the different 
 bones of the head skeleton. 
 
198 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 Bones 
 
 Of Intracartilaginous 
 Origin 
 
 Of Intramembranous 
 Origin 
 
 Derived from Visceral 
 Arches 
 
 Occipitale. 
 
 Pars basilaris. 
 Pars lateralis. 
 Squama occipitalis below 
 sup. nuchal line. 
 
 Squama occipitalis above 
 sup. nuchal line. 
 
 
 Temporale. 
 
 Pars mastoidea. 
 Pars petrosa, with proc- 
 essus sty-oideus. 
 
 Pars tvmpanica. 
 Squama temporalis. 
 
 Processus styloideus (second 
 arch). 
 
 Sphenoidale. 
 
 Corpus. 
 Ala parva. 
 Ala magna. 
 Hamulus pterygoideus. 
 
 Processus pterygoideus, ex- 
 cept hamulus pterygoi- 
 deus. 
 
 
 Ethmoidale. 
 
 Crista galli. 
 Lamina cribrosa. 
 Lamina perpendicularis. 
 Labyrinthus ethmoidalis. 
 
 
 
 Vomer. 
 
 
 Vomer. 
 
 
 Parietale. 
 
 
 Parietale. 
 
 
 Frontale. 
 
 
 Frontale. 
 
 
 Lacrimale. v 
 
 
 Lacrimale. 
 
 
 Nasale. 
 
 
 Nasale. 
 
 
 Zygoma. 
 
 
 Zygoma. 
 
 
 Maxilla. 
 
 
 Maxilla, with incisivum. 
 
 Maxilla, except mcisivum( ?) 
 (first arch). 
 
 Palatinum. 
 
 
 Palatinum. 
 
 Palatinum. 
 
 Mandibula. 
 
 Processus condyloideus, 
 tip of. 
 Processus coronoideus, 
 tip of. 
 Corpus, distal end of. 
 
 Processus condyloideus, ex- 
 cept tip. 
 Processus coronoideus, ex- 
 cept tip. 
 Corpus, except distal end. 
 Ramus. 
 
 Mandibula (first arch). 
 
 Hyoideum. 
 
 Hyoideum 
 
 
 Cornu majus (third arch). 
 Cornu minus (second arch). 
 Corpus (third arch). 
 
 Ossicula 
 auditus. 
 
 Incus. 
 Malleus. 
 Stapes, except basis (?). 
 
 Basis stapedis. 
 
 Incus (first arch). 
 Malleus (first arch). 
 Stapes, except basis (?) 
 (second arch). 
 
 The Appendicular Skeleton. 
 
 The growth of the limb buds and their differentiation into arm, forearm 
 and hand, thigh, leg and foot, along with the rotation which they undergo during 
 development, have been discussed in the chapter on the external form of the 
 body (p. 149). The metameric origin of the muscles of the extremities is 
 
THE CONNECTIVE TISSUES AND THE SKELETAL SYSTEM. 
 
 199 
 
 discussed in the chapter on the muscular system (Chap. XI). It has been 
 seen that the greater part of the axial skeleton is derived from the sclerotomes, 
 is preformed in cartilage, and maintains its segmental character throughout life. 
 It has also been seen that the head skeleton is in part preformed in cartilage, is in 
 part of intramembranous origin, and shows but a trace of segmental character, 
 and that only in the occipital region at a very early stage. The appendicular 
 skeleton is derived wholly from the embryonic connective tissue which forms the 
 cores of the developing extremities, and shows no trace of a segmental character. 
 Here also, as in the axial skeleton, three stages may be recognized a blastemal, 
 a cartilaginous (Fig. 181), and a final osseous. 
 
 Acromion Coracoid process 
 
 Scapula &fi 
 
 Radius 
 
 Metacarpal I 
 
 __ . : Large multangular 
 
 & (trapezium) 
 
 Navicular (scaphoid) 
 Lunate (semilunar) 
 
 Small multangular 
 (trapezoid) 
 
 Metacarpal IV 
 Capitate (os magnum) 
 Triquetral (cuneiform) 
 Hamatate (uncifonn) 
 
 FIG. 181. Cartilages of left upper extremity of a human embryo of 17 mm. Hagen. 
 
 In the region of the shoulder girdle a plate of cartilage appears in the em- 
 bryonic connective tissue which lies among the developing muscles dorso-lateral 
 to the thorax. This plate of cartilage is the forerunner of the scapula, and in 
 general resembles it in shape. During the eighth week of fcetal life a single 
 center of ossification appears and gives rise to the body and spine of the scapula. 
 After birth certain accessory centers appear and produce the coracoid process, the 
 supragknoidal tuber osity, the acromion process, and the inferior angle and verte- 
 bral margin (Fig. 182). Later the supraglenoidal fuses with the coracoid and 
 forms part of the wall of the glenoid cavity. About the seventeenth year the 
 single center formed by the union of these two fuses with the rest of the scapula. 
 
200 TEXT-BOOK OF EMBRYOLOGY. 
 
 At the age of twenty to twenty-five years all the other accessory centers unite 
 with the rest of the scapula to form the adult bone. 
 
 There are two views concerning the development of the da-vide: one that it 
 is of intracartilaginous origin, the other that it is of intramembranous origin. 
 Ossification begins during the sixth week, possibly from two centers. It is true 
 that the cartilage that appears around the centers is of a looser character than 
 the ordinary embryonic cartilage, but whether the centers appear in cartilage 
 seems not to have been determined. At the age of fifteen to twenty years a 
 sort of secondary center appears at the sternal end of clavicle and fuses with 
 the body about the twenty-fifth year. 
 
 The humerus, radius and ulna are preformed in cartilage (Fig. 181) and 
 develop as typical long bones. Ossification begins in each during the seventh 
 
 Bone 
 
 Cartilage 
 
 FIG. 182. Scapula of new-born child, showing primary center of ossification, and cartilage 
 (lighter shading) in which secondary centers appear. Bonnet. 
 
 week at a single center and proceeds in both directions to form the shaft. 
 During the first four years after birth epiphyseal centers appear for the head, 
 greater and smaller tuberdes, trochlea and epicondyles. All these secondary 
 centers unite with the shaft of the humerus when the growth of the individual 
 ceases. In the case of the radius and ulna a secondary center appears at each 
 end of each bone to form the epiphysis; and in the ulna another secondary 
 center appears to form the olecranon. (For the growth of bones, see page 176). 
 The carpal bones are all preformed in cartilage (Fig. 181) but their develop- 
 ment is somewhat complicated owing to the fact that pieces of cartilage appear 
 which subsequently may disappear, or ossify and become incorporated in other 
 bones. Primarily seven distinct pieces of cartilage develop and become ar- 
 ranged transversely in two rows; these represent seven of the carpal bones. 
 The proximal row consists of three large pieces which are the forerunners of the 
 navicular (radial, scaphoid), lunate (intermediate, semilunar) and triquetral 
 
THE CONNECTIVE TISSUES AND THE SKELETAL SYSTEM. 
 
 201 
 
 (ulnar, pyramidal, cuneiform) . The distal row is composed of four elements 
 which are the forerunners of the large multangular (trapezium), small multangu- 
 lar (trapezoid), capitate (os magnum), and hamatate or hooked (unciform). In 
 addition to the cartilages mentioned, several others also appear in an inconstant 
 way in different individuals. Two of these are important. One appears on 
 the ulnar side of the proximal row and is the forerunner of the pisiform; the 
 other is situated between the two rows and may either disappear entirely or fuse 
 with the navicular. Ossification does not begin in the carpal cartilages until 
 after birth; it begins in the hamatate and capitate during the third year, in the 
 
 Phalanges 
 
 Metacarpals 
 
 Large 
 multangular 
 
 Capitate 
 Navicular 
 
 Radius 
 
 FIG. 183. Skiagram of right hand of 5 year old girl. (Courtesy of Dr. Edward Learning). 
 The ossification centers are indicated by the darker areas. 
 
 others at later periods, and is completed only when the growth of the individ- 
 ual ceases. The fact that the hamatate ossifies from two centers indicates 
 that it is probably derived phylogenetically from two bones. Comparative 
 anatomy teaches that the accessory cartilages in the human wrist are repre- 
 sentatives of structures which are normally present in the lower forms. 
 
 The metacarpals and phalanges are preformed in cartilages which correspond 
 in shape to the adult bones. A center of ossification appears in each cartilage 
 and produces the shaft of the bone. Only one epiphysis develops on each 
 metacarpal and phalanx. In each metacarpal it develops at the distal end, 
 
202 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 Ilium 
 
 . 
 
 Crural nerve 
 
 Pubic bone (cartilage) 
 
 FIG. 184. Cartilage of right side of pelvic girdle of a human embryo of 13.6 mm. 
 
 (5 weeks). Peter sen. 
 The numerals indicate the vertebrae; the first sacral being opposite the ilium. 
 
 Ilium I 
 
 Crural nerve 
 
 Pubic bone (cartilage) 
 
 Obturator nerve 
 Ischium 
 
 Ischiadic nerve 
 
 FIG. 185. Cartilage of right side of pelvic girdle of a human embryo of 18.5 mm. 
 
 (8 weeks). Petersen. 
 
 The numerals indicate the vertebrae; the first and second sacral being opposite the ilium. 
 
 Compare with Fig. 184. 
 
THE CONNECTIVE TISSUES AND THE SKELETAL SYSTEM. 203 
 
 except in the thumb where it appears at the proximal end. In each phalanx it 
 develops at the proximal end (Fig. 183). 
 
 The skeletal elements of the low er extremities, including the pelvic girdle, are 
 of intracartilaginous origin. Each hip bone (os coxae, innominate bone) is pre- 
 formed in cartilage which, in a general way, resembles in shape the adult bone. 
 The ventral part of the pubic cartilage does not at first join the ischial; but by the 
 eighth week the junction is complete, leaving dorsal to it the obturator foramen. 
 In the earliest stages the long axis of the cartilage is nearly at right angles to the 
 vertebral column, and the ilium lies close to the fifth lumbar and first sacral 
 vertebras; later (eighth week) the long axis lies nearly parallel with the vertebral 
 column and the whole cartilage has shifted so that the ilium is associated with 
 the first three sacral vertebrae (Figs. 184 and 185). 
 
 Pubic bone 
 
 Ilium 
 
 Cartilage 
 
 FIG. 186 Right os coxae (innominate bone) of new-born child. Bonnet. 
 Bone is indicated by darker areas, cartilage by lighter areas. 
 
 Ossification begins at three centers which correspond to the ilium, ischium 
 and pubis; the center for the ilium appears during the eighth week, the centers 
 for the ischium and pubis several weeks later (Fig. 186). The process of ossifi- 
 cation is slow, and is far from complete at the time of birth, for at that time the 
 entire crest of the ilium, the bottom of the acetabulum and all the region ventral 
 to the obturator foramen are cartilaginous. During the eighth or ninth year 
 the ventral parts of the pubis and ischium become partly ossified, but up to the 
 time of puberty the pubis, ischium and ilium remain separated by plates of car- 
 tilage which radiate from a common center at the bottom of the acetabulum. 
 Soon after this, the three bones unite to form the single os coxae, leaving only the 
 crest of the ilium, the pubic tubercle and the sciatic tuber (tuberosity of the 
 ischium) cartilaginous. In each of these regions an accessory ossification cen- 
 
204 TEXT-BOOK OF EMBRYOLOGY. 
 
 ter appears and finally fuses with the corresponding bone about the twenty- 
 fourth year. 
 
 The femur, tibia andfibula are preformed in cartilage. In the femur a center 
 ,of ossification appears about the end of the sixth week and gives rise to the 
 shaft; similar centers appear in the tibia and fibula during the seventh and 
 eighth week, respectively. In the femur a distal epiphyseal center appears 
 shortly before birth, and during the first year after birth a proximal center 
 appears for the head. These centers do not unite with the shaft until the individ- 
 ual ceases to grow. The great and lesser trochanters also have accessory ossifica- 
 tion centers. In the tibia the center of ossification for the proximal epiphysis 
 appears about the time of birth, the one for the distal during the second year. In 
 
 Fibula \ -/-- Tibia 
 
 Calcaneus 
 
 .Talus 
 
 Cuboid ~^/7>N~NJ ^ 
 
 Cuneiform III*-J /f- / 7/V\ * Cuneiform I 
 
 Cuneiform II 
 
 Metatarsals 
 FIG. 187. Diagram of cartilages of left leg and foot of human embryo of 17 mm. Hagen. 
 
 the fibula the epiphyseal centers appear during the second and sixth years after 
 birth. The cartilage of the patella appears during the third or fourth month 
 of fcetal life, and ossification begins two or three years after birth. 
 
 The bones of the tarsus, like those of the carpus, are preformed in pieces of 
 cartilage which are arranged in two transverse rows. The proximal row con- 
 sists of three pieces, one at the end of the tibia (tibial), one at the end of the 
 fibula (fibular), and the third between the two (intermedial) . At an early stage 
 the tibial and intermedial fuse to form a single piece of cartilage which corre- 
 sponds to the talus (astragalus) bone. The fibular cartilage corresponds to the 
 calcaneus (os calcis). The distal row is composed of four pieces of cartilage 
 which correspond to the first cuneiform (internal), second cuneiform (middle), 
 third cuneiform (external), and cuboid (Fig. 187). Between the two rows is a 
 
THE CONNECTIVE TISSUES AND THE SKELETAL SYSTEM. 
 
 205 
 
 piece of cartilage which corresponds to the navicular (scaphoid). Ossification 
 begins relatively late in the metatarsals. A center for the calcaneus appears 
 during the sixth month of foetal life, and one for the talus shortly before birth. 
 Centers appear in the cuboid and third cuneiform during the first year after 
 birth, and in the first cuneiform, navicular and second cuneiform in order during 
 the third and fourth years (Figs. 188 and 189). At the age of puberty ossifica- 
 tion is nearly complete in all the metatarsals. In the talus two centers, cor- 
 responding to the tibial and intermedial, appear, but soon fuse into a single 
 center. Occasionally the intermedial remains separate and forms the trigonum. 
 
 Calcaneus 
 
 Phalanges 
 
 FIG. 188. Ossification centers in foot of a child 9 months old. Hassel-wander. 
 
 An accessory center appears in the calcaneus at the insertion of the tendon of 
 Achilles. 
 
 The metatarsals and phalanges develop in a manner corresponding to the 
 metacarpals and phalanges (of fingers). Ossification begins in the metatarsals 
 about the ninth week, in the first row of (proximal) phalanges about the 
 thirteenth week, in the second row about the sixteenth week and in the third 
 row (distal) about the beginning of the ninth week. Epiphyseal centers ap- 
 pear from the second to the eighth year after birth. 
 
 Development of Joints. 
 
 The embryonic connective tissue from which the connective tissues, includ- 
 ing cartilage and bone, are developed, at first forms a continuous mass. When 
 cartilage appears it may form a continuous mass, as in the chondrocranium, or 
 
206 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 it may form a number of distinct and separate pieces, as in the vertebral column, 
 the pieces being united by a certain amount of the undifferentiated embryonic 
 connective tissue. 
 
 SYNARTHROSIS. Syndesmosis. When ossification begins at one or more 
 centers, either in cartilage or in embryonic connective tissue, the centers grad- 
 ually enlarge and approach each other, and the bone so formed comes in contact 
 with the bone formed in neighboring centers, (a) In a case where more than one 
 center appears for any single adult bone, they may come in contact and fuse so 
 completely that the line of fusion becomes indistinguishable, (b) In the case of 
 
 Talus (astragalus) 
 
 Cuneiform II 
 
 Cuneiform I 
 
 Epiphysis of 
 metatarsal I 
 
 Metatarsal I 
 
 Calcaneus - , |_j / *\ 
 
 (oscalcis) \'& ft^ T7vT~~ 
 
 Cuboid 
 
 Metatarsal V 
 
 Epiphysis of 
 metatarsal V 
 
 Phalanx 
 
 Epiphyses of 
 phalanges 
 
 FIG. 189. Skeleton of right foot of a boy 3 years old, showing ossification centers. Toldt. 
 
 adjacent bones the fusion may not be so complete; that is, the two bones may 
 simply articulate, leaving a visible line of junction or suture. Such joints are 
 immovable and are represented in the sutures of the skull. 
 
 Synchondrosis. In some cases a small amount of embryonic connective 
 tissue remains between adjacent bones, (a) In time, this embryonic connective 
 tissue gives rise to cartilage which unites the bones quite firmly, thus producing 
 a practically immovable joint, as in the case of the sacro-iliac joint, (b) Or the 
 cells in the center of the cartilage disintegrate or become liquefied so that a small 
 cavity is produced (articular cavity). This type of joint makes possible a slight 
 degree of mobility and is exemplified by the symphysis of the pubic bones. Such 
 a type is also represented by the joints of the vertebral column. In place of 
 cavities, however, are the pulpy nuclei which are remnants of the notochord. 
 
THE CONNECTIVE TISSUES AND THE SKELETAL SYSTEM. 
 
 207 
 
 DIARTHROSIS. Where a great degree of mobility is necessary, the arrange- 
 ment of the joint is different. The cells in the central part of the embryonic 
 connective tissue between the ends of adjacent bones (or cartilages) (Fig. 190) 
 liquefy so that a relatively large cavity, the joint cavity, is formed (Fig. 191). 
 The liquefaction of the connective tissue cells may also extend for a short dis- 
 tance along the sides of the bones so that the joint cavity surrounds the ends 
 of the bones (Figs. 192 and 193). The origin of the synovial fluid is not known 
 
 Humerus 
 
 Radius 
 
 FIG. 190. Section through axilla and arm of a human embryo of 26 mm. (2 months). Photograph. 
 Note the mesenchymal tissue between the humerus and the radius the site of the elbow joint. 
 
 with certainty, but it is probably in part the product of liquefaction of the con- 
 nective tissue cells. The more peripheral part of the connective tissue which 
 encloses the joint cavity is transformed into a dense fibrous tissue, the joint 
 capsule. The cells lining the cavity become differentiated into oval or irregular 
 cells, among which is a considerable amount of intercellular substance. By 
 some it is held that these cells form a continuous single layer like endothelium, 
 but the most recent researches tend to disprove this. The cells lining the 
 
208 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 Joint cavity 
 
 FlG. 191. Longitudinal section of finger of human embryo of 26 mm. (2 months), showing beginning 
 of joint cavity between adjacent ends of phalanges. (Photograph from preparation by 
 Dr. W. C. Clarke.) 
 
 FIG. 192. From longitudinal section of finger of child at birth, showing developing joint cavity 
 between adjacent ends of phalanges. The darker portion at each end of the figure indicates 
 the ossification center in the phalanx, the end of the latter (lighter area) being yet cartilagi- 
 nous. The dark bands at each side of the joint indicate developing ligaments. Photograph. 
 
THE CONNECTIVE TISSUES AND THE SKELETAL SYSTEM. 209 
 
 cavity are the most highly differentiated, the cell bodies being large and ap- 
 parently swollen, and there is gradually less differentiation as the distance from 
 the surface increases, until finally they merge with the ordinary type of con- 
 nective tissue cells of the joint capsule (Clarke). The more mobile joints of 
 the body are all representatives of this type. 
 
 Joint cavity 
 
 Synovial membrane 
 
 FIG. 193. From longitudinal section of finger of child at birth, showing joint cavity and synovial 
 membrane between adjacent ends of the first metacarpal and proximal phalanx. Other 
 description same as in Fig. 192. Photograph. 
 
 Anomalies. 
 THE AXIAL SKELETON. 
 
 THE VERTEBRAE. The number of cervical vertebras in man is remarkably 
 constant. Cases where the number is but six are extremely rare. The 
 thoracic vertebrae may vary in number in different individuals from eleven to 
 thirteen, twelve being the usual number. The lumbar vertebrae may vary 
 from four to six, five being the usual number. The sacral vertebrae, fused in the 
 adult to form the sacrum, are usually five in number, sometimes four, sometimes 
 
210 TEXT-BOOK OF EMBRYOLOGY. 
 
 six. Occasionally a vertebra between the lumbar region and sacral region 
 lumbo-sacral vertebra possesses both lumbar and sacral characters, one 
 side being fused with the sacrum, the other side having a free transverse process. 
 Variation occurs frequently in the coccygeal vertebrae; four and five are present 
 with about equal frequency, more rarely there are only three. 
 
 The total number of true (presacral) vertebrae may be diminished by one or 
 increased by one. In the former case the first sacral is the twenty-fourth ver- 
 tebra, and, if the number of ribs remains normal, there are only four lumbar 
 vertebrae. In case the total number is increased by one, the first sacral is the 
 twenty-sixth vertebra, and there are twelve thoracic and six lumbar or thirteen 
 thoracic and five lumbar. 
 
 From these facts it is seen that variation occurs most frequently in the more 
 caudal portion of the vertebral column in the lumbar, sacral and coccygeal 
 regions. According to a hypothesis advanced by Rosenberg, the sacrum in the 
 earlier embryonic stages is composed of a more caudal set of vertebrae than those 
 which belong to it in the adult, and during development lumbar vertebras are 
 converted into sacral and sacral vertebrae into coccygeal. In other words, the 
 hip bone moves headward during development and finally becomes attached to 
 vertebrae which are situated more cranially than those with which it was pri- 
 marily associated. This change in the position of the pelvic attachment, and the 
 corresponding reduction in the total number of vertebrae, during the develop- 
 ment of the individual (i.e., during ontogenetic development) is believed to 
 correspond to a similar change in position during the evolution of the race (i.e., 
 during phylogenetic development). 
 
 According to Rosenberg, variation in the adult is due largely to a failure 
 during ontogeny to carry the processes of reduction in the number of vertebrae 
 as far as they are usually carried in the race, or to their being carried beyond this 
 point. 
 
 The coccygeal vertebrae apparently represent remnants of the more exten- 
 sively developed caudal vertebrae in lower forms. In human embryos of 8 to 
 16 mm., when the caudal appendage is at the height of its development, there 
 are usually seven anlagen of coccygeal vertebrae. During later development this 
 number becomes reduced by fusion of the more distally situated anlagen to the 
 smaller number in the adult. This process of reduction varies in different in- 
 dividuals, so that five or four, rarely three, coccygeal vertebrae may be the result. 
 In cases where children are born with distinct caudal appendages there is no 
 good evidence that the number of coccygeal vertebrae is increased, although the 
 coccyx may extend into the appendage. 
 
 THE RIBS. Occasionally in the adult a rib is present on one side or on 
 each side in connection with the seventh cervical vertebra (cervical rib), or in 
 connection with the first lumbar vertebra (lumbar rib). There seems to be no 
 
THE CONNECTIVE TISSUES AND THE SKELETAL SYSTEM. 211 
 
 case on record where cervical and lumbar ribs are present in the same individual. 
 The cervical rib may vary between a small piece of bone connected with the 
 transverse process of the vertebra and a well developed structure long enough to 
 reach the sternum. There are also great variations in the size of the lumbar rib. 
 In case the number of ribs is normal, the last (twelfth) may be rudimentary. 
 
 The eighth costal cartilage not infrequently unites with the sternum. Oc- 
 casionally the seventh costal cartilage fails to fuse with the sternum, owing to 
 the shortening of the latter, but meets and fuses with its fellow of the opposite 
 side in the midventral line. 
 
 The above mentioned anomalies can be referred back to aberrant develop- 
 ment. Primarily costal processes appear in connection with the cervical, lum- 
 bar and sacral vertebrae. Normally these processes fuse with and finally form 
 parts of the vertebrae (p. 185). In some cases, however, the seventh cervical or 
 the first lumbar processes develop more fully and form more or less distinct ribs. 
 
 As an explanation of these variations in the number of ribs, it has been sug- 
 gested that there is a tendency toward reduction in the total number of ribs, and 
 that supernumerary ribs represent the result of a failure to carry the reduction as 
 far as the normal number. In case the twelfth rib is rudimentary, the reduction 
 has been carried beyond the normal limit. This hypothesis is a corollary to the 
 hypothesis regarding the variations in the number of vertebrae. (See under 
 "The Vertebrae.") 
 
 THE STERNUM. Certain anomalous conditions of the sternum can also be 
 explained by reference to development. The condition known as cleft sternum, 
 in which the sternum is partially or wholly divided into two longitudinal bars 
 by a medial fissure, represents the result of a failure of the two bars to unite in 
 the midventral line (p. 185, see also Fig. 168). This is sometimes associated 
 with ectopia cordis (p. 286). The xyphoid process may also be bifurcated or 
 perforated, according to the degree of fusion between the two primary bars 
 (p. 186). 
 
 Suprasternal bones may be present. They represent the ossified episternal 
 cartilages which have failed to unite with the manubrium (p. 186). Morpho- 
 logically the suprasternal bones possibly represent the omosternum, a bone 
 situated cranially to the manubrium in some of the lower Mammals. 
 
 THE HEAD SKELETON. The skull is sometimes decidedly asymmetrical. 
 Probably no skull is perfectly symmetrical. The condition which most fre- 
 quently accompanies the irregular forms of skulls is premature synosteosis or 
 premature closure of certain sutures. The cranial bones increase in size prin- 
 cipally at their margins, and when a suture is prematurely closed the growth of 
 the skull in a direction at right angles to the line of suture is interfered with. 
 Consequently compensatory growth must take place in other directions. Thus 
 if the sagittal suture is prematurely closed and transverse growth prevented, 
 
212 TEXT-BOOK OF EMBRYOLOGY. 
 
 increase occurs in the vertical and longitudinal directions. This results in the 
 vault of the skull becoming heightened and elongated, like an inverted skiff, a 
 condition known as scaphocephaly. After premature closure of the coronal 
 suture, growth takes place principally upward and gives rise to acrocephaly. In 
 case only one-half the coronal or lambdoidal suture is closed, the growth is 
 oblique and results in plagiocephaly. 
 
 A suture the metopic suture sometimes exists in the medial line between 
 the two halves of the frontal bone, a condition known as metopism. This is due 
 to an imperfect union of the two plates of bone produced by the two centers of 
 ossification in the frontal region (p. 194). 
 
 Certain malformations in the face region and in the roof of the mouth are 
 brought about by defective fusion or complete absence of fusion between certain 
 structures during the earlier embryonic stages. The maxillary process of the 
 first branchial arch sometimes fails to unite with the middle nasal process 
 (Kolliker's view, p. 196; see also Fig. 136). The result is a fissure in the 
 upper lip, a condition known as hare lip, which may or may not be accompanied 
 by a cleft in the alveolar process of the maxilla, extending as far as the incisive 
 (palatine) foramen. The same result may be produced by a defective fusion 
 between the middle nasal process and the lateral nasal process (Albrecht's view, 
 p. 196; see also Fig. 136). Hare lip may be either unilateral (single) or bilateral 
 (double), accordingly as defective fusion occurs on one or both sides, but never 
 medial. 
 
 Occasionally the palatine process of the maxillary process fails to meet not 
 only its fellow of the opposite side, but also the vomer (see Fig. 1 79) . The result 
 is a cleft in the hard palate, a condition known as cleft palate. This malforma- 
 tion may be unilateral or bilateral, but not medial. Sometimes the cleft extends 
 into the soft palate where it occupies, however, a medial position. 
 
 Cleft palate may accompany hare lip, or either may exist without the other, 
 depending upon the degree of fusion between the processes mentioned above. 
 In bilateral hare lip, with or without cleft palate, the incisive (intermaxillary) 
 bone is sometimes pushed forward by the vomer and projects beyond the surface 
 of the face, a condition known as "wolf's snout." 
 
 The causes underlying the origin of hare lip and cleft palate are very obscure. 
 
 THE APPENDICULAR SKELETON. 
 
 THE HUMERUS. On the medial side of the humerus, just proximal to the 
 medial condyle, there is not infrequently a small hook-like process directed 
 distally the supracondyloid process. This process represents a portion of bone 
 which in some of the lower mammals (cat, for example) joins the internal 
 condyle and completes the supracondyloid foramen, through which the median 
 nerve and brachial artery pass. 
 
THE CONNECTIVE TISSUES AND THE SKELETAL SYSTEM. 213 
 
 THE CARPAL BONES. Occasionally an os centrale is present in addition to 
 the usual carpal bones. It is situated on the dorsal side of the wrist between the 
 navicular, capitate and small multangulum. In the embryo an additional piece 
 of cartilage is of constant occurrence in this location, but usually disappears 
 during later development; in cases where it persists, ossification takes place 
 to form the os centrale. In some of the apes the os centrale is of constant 
 occurrence in the adult. 
 
 THE FEMUR. The gluteal tuberosity (ridge) sometimes projects like a 
 comb, forming the so-called third trochanter, a structure homologous with the 
 third trochanter in the horse and some other mammals. 
 
 THE TARSAL BONES. Cases have been recorded in which the total number 
 of tarsal bones was reduced, owing to congenital synosteosis (fusion) of the 
 calcaneus (os calcis) and scaphoid (navicular), of the talus (astragalus) and 
 calcaneus, or of the talus and scaphoid. Occasionally an additional bone the 
 trigonum is present at the back of the talus. In the embryo, the talus ossifies 
 from two centers which normally fuse at an early stage into a single center. 
 The trigonum probably represents a bone produced by one of the centers which 
 has remained separate. 
 
 POLYDACTYLY. This anomaly consists of an increase in the number of 
 fingers or toes, or both. Any degree of variation may exist from a supernum- 
 erary finger or toe to a double complement of fingers or toes. The causes under- 
 lying the origin of such anomalies are not clear. Some assign the supernumer- 
 ary digits to the category of pathological growths or neoplasms, linking them 
 with partial duplicate formations. Others explain the extra digits on the ground 
 of atavism or reversion to an ancestral type. The latter explanation assumes 
 an ancestral type with more than five digits. But neither zoology nor paleon- 
 tology has found any vertebrate form, above the Fishes, which normally pos- 
 sesses more than five digits on each extremity. Consequently one must refer to 
 the Fishes for some ancestral type to explain the existence of more than five 
 digits. Going back so far in phylogenetic history, no certainty whatever can be 
 attached to the origin of supernumerary digits, for it is not even known from 
 what fins the extremities of the higher forms are derived. Still another view 
 regarding the origin of supernumerary digits is that they are due to certain ex- 
 ternal influences among which the most important is the mechanical impression 
 of amniotic folds or bands. This, however, could not be the sole cause of 
 polydactylism, since such malformations are common in amphibian embryos 
 where no amnion is present. 
 
 References for Further Study. 
 
 ADOLPHI, H. : Ueber die Variationen des Brustkorbes und der Wirbelsaule des Menschen. 
 Morph. Jahrbuch, Bd. XXIII, 1905. 
 
214 TEXT-BOOK OF EMBRYOLOGY. 
 
 BADE, P.: Die Entwickelung des menschlichen Skeletts bis zur Geburt. Arch. /. mik. 
 Anat. t Bd. LV, 1900. 
 
 BARDEEN, C. R.: Numerical Vertebral Variations in the Human Adult and Embryo. 
 Anat. Anz., Bd. XXV, 1904. 
 
 BARDEEN, C. R.: Studies of the Development of the Human Skeleton. American 
 Jour, of Anat., Vol. IV, 1905. 
 
 BARDEEN, C. R.: The Development of the Thoracic Vertebra in Alan. American 
 Jour, of Anat., Vol. IV, 1*905. 
 
 BARTELS, M.: Ueber Menschenschwanze. Arch. /. Anthropol., Bd. XII. 
 
 BERNAYS, A.: Die Entwickelungsgeschichte des Kniegelenkes des Menschen mit 
 Bemerkungen iiber die Gelenke im allgemeinen. Morph. Jahrbuch, Bd. IV, 1878. 
 
 BOLL, F.: Die Entwickelung des fibrillaren Bindegewebes, Arch. /. mik. Anat., Bd. 
 VIII, 1872. 
 
 BOLK, L.: Beziehungen zwischen Skelett, Muskulatur und Nerven der Extremitaten, 
 etc. Morph. Jahrbuch, Bd. XXI, 1894. 
 
 BONNET, R.: Lehrbuch der Entwickelungsgeschichte. Berlin, 1907. 
 
 BRATJS, H.: Die Entwickelung der Form der Extremitaten und des Extremitatenskeletts. 
 In Hertwig's Handbuch der vergleich. u. experiment. Entwickelungslehre der Wirbeltiere, Bd. 
 Ill, Teil II, 1904. 
 
 BROWN, ALFRED J.: The Development of the Vertebral Column in the Domestic 
 Cat. Anat. Record, Vol. X, No. 3, 1916. 
 
 FAWCETT, E.: On the Early Stages in the Ossification of the Pterygoid Plates of the 
 Sphenoid Bone of Man. Anat. Anz., Bd. XXVI, 1905. 
 
 FAWCETT, E. : Ossification of the Lower Jaw in Man. Jour. Amer. Med. Assoc., Bd. XLV, 
 1905. 
 
 FAWCETT, E.: On the Development, Ossification and Growth of the Palate Bone. Jour, 
 of Anat. and Physiol., Bd. XL, 1906. 
 
 FLEMMING, W. : Die Histogenese der Stiitzsubstanzen der Bindesubstanzgruppe. In 
 Hertwig's Handbuch der vergleich. u. experiment. Entwickelungslehre der Wirbeltiere, Bd. Ill, 
 Teil II, 1901. 
 
 FLEMMING, W.: Morphologic der Zelle. Ergebnisse der Anat. u. Entwick., Bd. VII, 
 1897. 
 
 GAUPP, E.: Alte Probleme und neuere Arbeiten iiber den Wirbeltierschadel. Ergebnisse 
 der Anat. u. Entwick., Bd. X, 1901. 
 
 GAUPP, E.: Die Entwickelung des Kopfskeletts. In Hertwig's Handbuch der vergleich. 
 u. experiment. Entwickelungslehre der Wirbeltiere, Bd. Ill, Teil II, 1905. 
 
 GEGENBAUR, C.: Die Metamerie des Kopfes und die Wirbeltheorie des Kopfskeletts. 
 Morph. Jahrbuch, Bd. XIII, 1887. 
 
 GR^EFENBERG, E.: Die Entwickelung der Knochen, Muskeln und Nerven der Hand 
 und der fiir die Bewegungen der Hand bestimmten Muskeln des Unterarms. Anat. Hefte, 
 Heft XC, 1905. 
 
 HAGEN, W.: Die Bildung des Knorpelskeletts beim menschlichen Embryonen. Arch. 
 j. Anat. u. Physiol., Anat. Abth., 1900. 
 
 HANSEN, C.: Ueber die Genese einiger Bindegewebsgrundsubstanzen. Anat. Anz., 
 Bd. XVI, 1899. 
 
 HASSELWANDER, A.: Untersuchungen iiber die Ossification des menschlichen Fuss- 
 skeletts. Zeitschr. f. Morphol. u. Anthropol., Bd. V, 1903. 
 
 HERTWIG, O.: Lehrbuch der Entwickelungsgeschichte des Menschen u. der Wirbeltiere. 
 Jena, 1906. 
 
THE CONNECTIVE TISSUES AND THE SKELETAL SYSTEM. 215 
 
 JAKOBY, M.: Beitrag zur Kenntniss des menschlichen Primordialcraniums. Arch. f. 
 mik. Anal., Ed. XLIV, 1894. 
 
 KEIBEL, F.: Ueber den Schwanz des menschlichen Embryo. Arch. f. Anal. u.Physiol., 
 Anat. Abth., 1891. 
 
 KEIBEL, F.: Zur Entwickelungsgeschichte der Chorda bei Saugern. Arch. f. Anat. 
 u. Physiol., Anat. Abth., 1889. 
 
 KEIBEL, F., and MALL, F. P.: Manual of Human Embryology, Vol. I, 1910. Chap. XI. 
 
 KJELLBERG, K.: Beitrage zur Entwickelungsgeschichte des Kiefergelenks. Morph. 
 Jahrbuch, Ed. XXXII, 1904. 
 
 KOLLHAXX, J.: Entwickelung der Chorda dorsalis bei dem Menschen. Anat. Anz., 
 Ed. V, 1890. 
 
 KoLLiiANN, J.: Lehrbuch der Entwickelungsgeschichte des Menschen. Jena, 1898. 
 
 KOLLMANN, J.: Handatlas der Entwickelungsgeschichte des Menschen. Jena, 1907. 
 
 MALL, F. P.: The Development of the Connective Tissues from the Connective-tissue 
 Syncytium. American Jour, of Anat., Bd. I, 1902. 
 
 ]\IALL, F. P. : On Ossification Centers in Human Embryos less than One Hundred Days 
 Old. American Jour, of Anat., Ed. V, 1906. 
 
 McMuRRicn, J. P.: The Development of the Human Body. Philadelphia, 1907. 
 
 PATERSOX, A.: The Sternum: Its early Development and Ossification in Man and 
 Mammals. Jour, of Anat. and Physiol., Vol. XXXV, 1901. 
 
 PETERSEX, H.: Untersuchungen zur Entwickelung des menschlichen Beckens. Arch, 
 f. Anat. u. Physiol., Anat. Abth., 1893. 
 
 RABL ? C.: Theorie des Mesoderms. Morph. Jahrbuch, Ed. XV, 1889. 
 
 ROSEXBERG, E.: Ueber die Entwickelung der Wirbelsaule und das Centrale carpi des 
 Menschen. Morph. Jahrbuch, Ed. I, 1876. 
 
 SCHAUIXSLAXD, H.: Die Entwickelung der Wirbelsaule nebst Rippen und Brustbein. 
 In Hertwig's Handbuch der vergleich. u. experiment. Entwickelungslehre der Wirbeliiere, 
 Ed. Ill, Teil II, 1905. 
 
 SPULER, A.: Beitrage zur Histologie und Histogenese der Binde- und Stiitzsubstanz. 
 Anat. He jte, Heft XXI, 1896. 
 
 THILEXIUS, G.: Untersuchungen iiber die morphologische Bedeutung accessorischer 
 Elemente am menschlichen Carpus (und Tarsus). Morph. Arbeiten, Bd. V, 1896. 
 
 THOMSOX, A.: The Sexual Differences of theFcetal Pelvis. Jour, of Anat. and Physiol., 
 Vol. XXXIII, 1899. 
 
 TORXIER, G.: Das Entstehen der Gelenkformen. Arch. /. Entw.-Mechanik, Bd. I, 
 1895. 
 
 WALDEYER, W.: Kittsubstanz und Grundsubstanz, Epithel und Endothel. Arch. f. 
 mik. Anat., Ed. LVII, 1900. 
 
 WEISS, A. : Die Entwickelung der Wirbelsaule der weissen Ratte, besonders der vorder- 
 sten Halswirbel. Zeitschr. f. ivissensch. Zool., Ed. LXIX, 1901. 
 
 ZIMMERMANN, K.: Ueber Kopfhohlenrudimente beim Menschen. Arch. f. mik. Anat., 
 Ed. LIII, 1899. 
 
CHAPTER X. 
 
 THE DEVELOPMENT OF THE VASCULAR SYSTEM. 
 THE BLOOD VASCULAR SYSTEM. 
 
 The blood vessels constitute such an extensive and complex system that 
 it is obviously beyond the scope of this book to consider the entire system in 
 detail. Consequently attention must be directed only to the develop- 
 ment of the main channels, including the heart, and to the principles of 
 vessel formation. 
 
 a b 
 
 FIG. 194. Surface views of chick blastoderms. Rtickert, Hertwig. 
 
 a, Blastoderm with primitive streak and head process; showing blood islands (dark spots in 
 
 crescent-shaped area in lower part of figure). 
 
 b, Blastoderm with 6 pairs of primitive segments. Reticulated appearance is due to blood 
 
 islands (dark spots) and to developing vessels, the entire reticulated area being the area 
 vasculosa. 
 
 The formation of blood vessels in all the higher vertebrates including 
 mammals begins in the opaque area of the blastoderm (area opaca) while 
 the germ layers still lie flat. Toward the end of the first day of incubation 
 in the chick, about the time the primitive streak reaches the height of its 
 
 216 
 
THE DEVELOPMENT OF THE VASCULAR SYSTEM 
 
 217 
 
 development, the peripheral part of the area opaca caudal and lateral to the 
 primitive streak presents a mpttled appearance (Fig. 1940). This indicates 
 the beginning of the area vasculosa, which subsequently extends forward in 
 the peripheral portion of the opaque area, lateral to the developing body, 
 and becomes reticulated in appearance (Fig. 1946). 
 
 Sections of the blastoderm show that the mottled surface appearance is 
 due to clusters of cells amidst the mesoderm, known as blood islands (Fig. 
 195). These are composed of rounded cells which have developed from the 
 branched mesodermal (mesenchymal) cells, and are situated in close apposi- 
 tion to the entoderm. Subsequently, when the ccelom appears in this region, 
 they lie in the visceral, or splanchnic, layer of mesoderm (Fig. 196). 
 
 Ectoderm' 
 Mesoderm 
 
 Entoderm 
 (yolk cells) 
 
 Blood island 
 
 FIG. 195. Section of blastoderm (area opaca) of chick of 27 hours' incubation. Photograph. 
 
 The early changes that occur in the blood islands are important as re- 
 gards both developing vessels and blood cells. The superficial cells of an 
 island are transformed into flat cells placed edge to edge which surround 
 the remaining rounded cells. The flat cells constitute the endothelium of a 
 primitive blood space, while the cells within the space comprise primitive 
 blood cells (Fig. 196). These early spaces in the area vasculosa join one 
 another and become continuous to form a net-work, or plexus, of channels 
 to which is due the reticulated appearance referred to above (Fig. 1946). 
 This is known as the vitelline plexus. The groups of primitive blood cells 
 within the channels will be considered in detail in a subsequent section 
 (page 268). 
 
 During the second day of incubation in the chick the peripheral 
 
218 
 
 TEXT-BOOK OF EMBRYOLOGY 
 
 channels of the vascular area unite to form a vessel the sinus terminalis 
 which is continuous around the border except at the head end of the embryo 
 (Fig. 197). At the same time the vascularization of the visceral layer of 
 mesoderm gradually extends through the clear area of the blastoderm 
 (area pellucida) toward and finally into the embryonic body. Reaching 
 the region just lateral to the notocord, the vessels unite longitudinally in the 
 embryo to form a continuous channel, the primitive aorta, which thus con- 
 stitutes a natural selvage to the vascular area on each side of the blastoderm 
 (Fig. 197). Some of the channels of the vitelline plexus increase in size 
 and coalesce to form a large trunk which is a branch of the primitive aorta 
 
 Ccelom 
 
 Parietal mesoderm 
 
 Ectoderm 
 
 
 Visceral mesoderm 
 
 Blood islands 
 
 FIG. 196. Section of blastoderm of chick of 42 hours' incubation. Photograph. The cells of 
 the blood islands are differentiated into primitive blood cells and the endothelium of 
 the vessels. 
 
 on each side and leads off into the smaller vessels in the peripheral part of 
 the vascular area. This trunk is known as the vitelline, or omphalomesenteric, 
 artery and is at first located near the caudal end of the embryo. When cir- 
 culation is established through contractions of the heart it carries blood 
 from the aorta to the surface of the yolk sac (Fig. 197). Other channels of 
 the vitelline plexus nearer the head end of the embryo likewise form a large 
 trunk, the vitelline, or omphalomesenteric, vein which collects the blood from 
 the surface of the yolk sac and conveys it to the heart (Fig. 197). 
 
 So long as the germ layers lie flat the two primitive aortae remain separate, 
 but with the ventral flexion and fusion of the germ layers to form the tubular 
 body the aortae fuse into a single medial vessel, the dorsal aorta, except in 
 the cervical region where the two original vessels persist as the dorsal aortic 
 roots. The proximal ends of the vitelline arteries also fuse into a single 
 
THE DEVELOPMENT OF THE VASCULAR SYSTEM 
 
 219 
 
 trunk, the two vitelline veins, however, remaining separate. In each 
 branchial arch on each side a vessel develops which joins with the corre- 
 sponding dorsal aortic root. These vessels the aortic arches arise from a 
 single vessel on each side ventral to the pharynx which is known as the 
 ventral aortic root. The two ventral aortic roots arise from a single medial 
 
 FIG. 197. Dorsal surface view of chick embryo with 18 segments, including the area vasculosa. 
 Photograph, X 15. The blood vessels were injected with India ink, the dark blotch in 
 the upper left corner indicating some ink which escaped during the injection. 
 
 vessel, the aortic trunk, or truncus arteriostis, which in turn is a continuation 
 of the early tubular heart. 
 
 The heart, having developed and become a contractile organ in the 
 meantime, receives the blood in its caudal end through the vitelline veins 
 and ejects it from its cephalic end through the aortic trunk. The blood 
 then passes through the aortic arches to the dorsal aorta whence it is dis- 
 tributed to the vitelline plexus by the vitelline arteries. The blood is 
 
220 
 
 TEXT-BOOK OF EMBRYOLOGY 
 
 collected by tributaries of the vitelline veins and carried to the heart. Thus 
 the vitelline (yolk) circulation is completed (Fig. 198). From this time on, 
 the area vasculosa gradually enlarges, as the germ layers extend farther and 
 farther around the yolk, until it eventually surrounds the whole yolk mass. 
 In mammals, as in the chick, the vascular rudiments develop first in the 
 extraembryonic portion of the mesoderm as clusters of cells which give the 
 area opaca a mottled appearance on surface view. This soon changes to a 
 reticulated appearance as the cell clusters give rise to primitive blood spaces 
 which join one another to form a plexus of channels. This plexus gradually 
 
 Aortic arches 
 
 Sinus terminalis 
 
 Heart 
 
 Sinus // 
 terminalis ' /;/ 
 
 Ant. cardinal 
 vein 
 
 Aorta 
 
 Right vitelline vein 
 
 Right vitelline artery 
 
 If Duct cf Cuviev 
 
 Pest, cardinal vein 
 Left vitelline artery 
 
 Left vitelline vein 
 
 FIG. 198. Diagram of the vitelline (yolk) circulation of a chick embryo at the end of 
 the third day of incubation. Ventral view. Balfotir. 
 
 extends across the area pellucida toward the embryo and terminates in a 
 natural selvage as the primitive aorta on each side of the median line. The 
 vitelline arteries and veins are formed out of the plexus and, with the heart, 
 aortic arches and dorsal aorta as in the chick, constitute the vitelline cir- 
 culatory system (Fig. 199). The vascular area in some mammals gradually 
 enlarges until it embraces the entire yolk sac (Fig. 200). 
 
 It is seen from the foregoing account that the earliest circulation is asso- 
 ciated with the yolk sac. In animals below the mammals, where a large 
 amount of yolk is present in the sac, the vitelline circulation is of prime 
 
THE DEVELOPMENT OF THE VASCULAR SYSTEM 
 
 221 
 
 FIG. 199. Surface view of area vasculosa of a rabbit embryo of 1 1 days, van Beneden and Julin. 
 The vessel around the border is the sinus terminalis; the two large vessels above the embryo are 
 
 the vitelline (omphalomesenteric) veins ; the two large vessels converging below the 
 
 embryo are the vitelline (omphalomesenteric) arteries. 
 
 Chorionic villi 
 
 FIG. 200. Human embryo of 3.2 mm. His. The arrows indicate the direction 
 
 of the blood current. 
 
222 
 
 TEXT-BOOK OF EMBRYOLOGY 
 
 importance in supplying the growing embryo with nutritive materials. In 
 mammals the vitelline circulatory system develops as extensively as in the 
 lower forms but, since little yolk is present, does not assume the same impor- 
 tant role of carrying food supply ; yet the portions of the vessels inside the em- 
 bryo, viz. : the heart, aortic arches, aorta, the proximal part of the vitelline 
 artery, and the vitelline veins, form parts of the permanent vascular system. 
 In reptiles and birds a second set of vessels develops in connection with 
 the allantois and serves to carry away the waste products of the body and 
 deposit them in that sac-like structure. Two arteries, one on each side, 
 
 Gut 
 
 Umbilical vein 
 
 Amnion 
 
 Allantois 
 
 Yolk stalk 
 
 Umbilical artery 
 Umbilical vein 
 
 Amnion 
 
 Chorionic villi 
 
 FIG. 201. Diagram of the umbilical vessels in the belly stalk and chorion. Kollmann's Atlas. 
 
 arise as branches of the dorsal aorta near its caudal end and pass out of the 
 body along with the allantoic duct to ramify upon the surface of the allantois. 
 These are the umbilical, or allantoic, arteries. The blood is collected and 
 carried back by the umbilical veins which pass along the allantoic duct to the 
 body and then forward, one on each side, through the somatic layer of 
 mesoderm to join the ducts of Cuvier. The duct of Cuvier, formed on each 
 side by the junction of the anterior and posterior cardinal veins, which will 
 be considered in a subsequent section, pour their blood into the sinus venosus. 
 This venous trunk is formed by the junction of the ducts of Cuvier with the 
 vitelline veins and empties directly into the heart. 
 
THE DEVELOPMENT OF THE VASCULAR SYSTEM 
 
 223 
 
 In mammals in general the allantois is a rudimentary structure incapable 
 of receiving the total waste of the embryo. The umbilical (allantoic) 
 vessels develop, however, as in reptiles and birds but become associated 
 through the belly stalk with the placenta which establishes communication 
 between the embryo and the mother (Fig. 201). The vessels within the 
 embryo are at first disposed in the same manner as in the lower forms, 
 
 Int. carotid artery 
 
 Vertebral artery 
 
 Vitelline vein 
 Vitelline artery 
 
 Umbilical vein 
 
 Umbilical 
 
 arteries 
 
 Duct of Cuvier 
 
 Post, cardinal 
 vein 
 
 \ 
 
 'Aorta 
 
 Post, cardinal vein 
 
 FIG. 202. Reconstruction of a human embryo of 7 mm. Mall. 
 
 Arteries represented in black. A.V., Auditory vesicle; B, bronchus;!,, liver; K, anlage of 
 kidney; T, thyreoid gland; III-XII, cranial nerve roots; i, 2, 3, 4, branchial grooves; i, 
 8, 12, 5 (on spinal nerve roots), ist and 8th cervical, i2th dorsal, 5th lumbar spinal nerves 
 respectively. Dotted outlines represent limb buds. 
 
 the umbilical arteries arising from the caudal portion of the aorta and the 
 umbilical veins passing forward in the ventro-lateral body wall to join the 
 ducts of Cuvier. With the formation of the umbilical cord the two umbilical 
 veins within this structure fuse into a single vessel (Fig. 202). The later 
 changes in the umbilical veins are most conveniently considered subsequently. 
 In mammals in general the umbilical (allantoic) circulatory system 
 performs a two-fold function. The blood carries to the placenta the waste 
 
224 TEXT-BOOK CF EMBRYOLOGY 
 
 products of the embryo for deposition in the maternal circulation, the waste 
 in the lower forms (reptiles and birds) being deposited in the allantois. 
 The blood carries from the placenta the food materials derived from the 
 maternal circulation, the food in the lower forms being taken from the yolk 
 sac and conveyed to the embryo by the vitelline vessels. 
 
 Principles of Vasculogenesis. Upon the thesis that tissues in general 
 must receive materials which they build up into their own substances and 
 must discharge the products of their activities, the vascular channels of 
 the body can be considered as structural expressions of this functional 
 necessity. For instance, a muscle which acts must receive materials to 
 compensate it for its loss and must discharge the waste products that result 
 from its action, and the blood vessels are peculiarly adapted to these func- 
 tions. The lymph vessels, too, similar in structure to the blood vessels, 
 although efferent relative to the tissues, play their part in conveying the 
 products of metabolism. 
 
 Much controversy has arisen over the actual genesis, or origin, of blood 
 vessels and lymphatics, and as yet the opposing views have not been recon- 
 ciled. In brief there are two views: One that with a few exceptions every 
 vessel in the body develops as a sprout from another vessel, that is, the 
 endothelium arises from preexisting endothelium by proliferation of its own 
 cells; the other that vessels in general arise in situ, that is, the lumen of a 
 vessel represents an intercellular tissue space, or several such spaces, whose 
 bordering cells have been transformed into the characteristic endothelial 
 cells, and as a corollary, the continuity of a given vessel results from the 
 union of such spaces. According to the latter view, the whole vascular 
 system represents intercellular tissue spaces which, with their lining of 
 flattened cells, have united to form a set of continuous channels. 
 
 In the case of either view it is recognized that the first vessels appear 
 in the opaque area of the blastoderm. Here the blood islands originate as 
 clusters of cells amidst the mesoderm, differentiating from mesenchymal 
 elements in close approximation to the entoderm (Fig. 195). The superficial 
 cells of the clusters are then transformed into flat cells placed edge to edge 
 to form the endothelial wall of a primitive blood space. These blood 
 spaces join one another and thus form a net-work of channels. From this 
 point in development the two views diverge. 
 
 The evidence adduced in favor of either theory is too great in volume 
 to set down here. The advocates of the theory of sprouting of the endo- 
 thelium lay stress upon the evidence of injected specimens. By injecting 
 developing blood vessels at successive stages it is found that the vascular 
 field gradually becomes larger, and the inference is that the individual 
 channels are extending farther and farther from the focus of origin through 
 
THE DEVELOPMENT OF THE VASCULAR SYSTEM 225 
 
 proliferation and migration of the endotheiial elements. This method, of 
 course, would demonstrate vessels only so far as the lumina are continuous. 
 Solid cords of cells which extend beyond the field of injection are interpreted 
 as cords of endotheiial cells which subsequently acquire lumina and become 
 capillary tubes. If this theory is correct then the vascularization of the 
 area pellucida and of the embryonic body would be effected through true 
 outgrowths of the original endothelium of the opaque area. Possible 
 exceptions to this, as noted above, are the rudiments of the heart, the aorta 
 and the cardinal veins which arise in situ as do the first vascular rudiments. 
 Observations upon growing vessels in living embryos, in which strands 
 of cells were seen to extend from the endothelium already present, have 
 also been accepted as evidence in favor of this view. 
 
 The evidence afforded by injected specimens has been attacked by those 
 who believe in the in situ origin of vessels, on the ground that the injection 
 shows only vessels with continuous lumina and does not prove the non- 
 existence of isolated vascular rudiments beyond the field of injection. It is 
 claimed that the vascular field becomes more extensive through the gradual 
 addition of such isolated spaces to the channels already continuous, in the 
 same manner that the primitive blood spaces unite to form a network, and 
 the claim is supported by demonstration of these spaces in the mesenchymal 
 tissue with every gradation between the bordering flattened cells (endo- 
 thelium) and the branching irregular mesenchymal cells. The actual 
 formation of intercellular spaces with flat bordering cells and their union 
 with vascular channels have been observed in the living chick blastoderm. 
 Experimental evidence has also been brought to bear in favor of the view 
 that vessels arise in situ. The area opaca was entirely removed from the 
 chick blastoderm before any vascular rudiments had appeared in the area 
 pellucida and the blastoderm was then allowed to develop further; it was 
 found that vascular rudiments appeared both in the area pellucida and 
 embryonic body with practically the same disposition as in the normal 
 embryo. 
 
 The concept that the vascular channels are structural expressions of the 
 functional necessity of carrying nutritive materials to the tissues and waste 
 products away from them leads to consideration of such factors as may be 
 involved in the formation of vessels; that is, factors that would cause plastic 
 cells, like those of the mesenchyme in which the earliest and simplest vessels 
 appear, to change in character and rearrange themselves to form capillary 
 tubes. In a mass of mesenchymal tissue, in which there is a resemblance 
 to a sponge with the cellular elements representing the parenchyma of the 
 sponge and the intercellular tissue spaces the interstices, the products of 
 cell activity naturally accumulate in the intercellular spaces. Incident 
 
226 TEXT-BOOK OF EMBRYOLOGY 
 
 to this accumulation, pressure would be exerted upon the cells bordering 
 the spaces. Seeking outlet from the confines of the spaces, the waste 
 products would move, or now, and cause friction against the cells past 
 which they flow. Similarly, pressure and friction would result from the 
 movement of nutritive materials to and through the tissue. The plastic 
 mesenchymal cells, reacting to these mechanical influences, would tend to 
 become flat, and the continued operation of the factors would result in a 
 smooth-walled tube in which the movement of fluid is greatly facilitated. 
 
 The reaction of the irregular mesenchymal cells to the mechanical in- 
 fluences of pressure and friction is, of course, the crux of the question. It 
 has been shown experimentally that cells of this type do react to mechanical 
 stimuli. Smooth non-irritating foreign bodies have been imbedded in the 
 loose connective tissue of an animal and the cells in contact therewith be- 
 came flat and formed a mosaic apparently identical with simple squamous 
 epithelium or endothelium. In the growth of mesenchymal tissue outside 
 of the body (in vitro) it has been observed that the cells flatten against 
 foreign substances which may be present. 
 
 In the embryo it has been observed that where blood vessels disappear, 
 which they do in certain regions, the endothelium does not degenerate but 
 that the cells assume irregular branching forms. This would indicate that 
 endothelium comprises merely modified mesenchymal cells and that upon 
 removal of the factors incident to the pressure and friction of blood flow 
 the cells reassume the indifferent character of mesenchyme, thus reverting 
 to the mesenchymal type. It militates, therefore, against the view that 
 endothelium is a specific tissue. 
 
 It is generally recognized, whether or not the endothelium originates 
 in situ, that a capillary network precedes the formation of larger vessels. 
 For instance, the vitelline plexus of capillaries (p. 217) antedates any of the 
 larger vitelline vessels which later carry blood to and from the embryo. 
 The establishment of vascular trunks in this plexus of small vessels seems to 
 be dependent upon the same mechanical factors that were considered as 
 operative in the origin of vessels; viz.: pressure and friction. If the volume 
 of blood that flows through a given capillary network at a given rate is in- 
 creased the flow will naturally follow the channels that offer the least re- 
 sistance, and these channels will increase in size sufficiently to accommodate 
 the greater volume. A few channels, or perhaps even only one, will form the 
 most direct course, and the angles in the course will be still further reduced 
 as the blood stream impinges upon the walls of the vessels. In this manner 
 a large vessel, or main vascular trunk, is established and the remaining 
 smaller vessels constitute its branches or tributaries. A rather crude analogy 
 would be the draining of a swamp in which a small rivulet, once gaining 
 
THE DEVELOPMENT OF THE VASCULAR SYSTEM 227 
 
 slight supremacy over its fellows, would gradually cut its way deeper into 
 the soil and pursue a straighter course, with the result that the other rivulets 
 would flow into it as the main channel. 
 
 The concept that the main vascular trunks are preceded by a capillary 
 plexus, out of which they develop in response to certain mechanical stimuli, 
 offers a simple explanation of the numerous variations found in the vascular 
 system. In the incipient stages of the larger vessels but slight influences, 
 due to variations in the development of surrounding structures, would be 
 sufficient to deflect their courses and cause them to occupy positions which 
 do not accord with the normal. So far as the thickened walls of the larger 
 vascular channels are concerned, they may be regarded as structural adapta- 
 tions to the functions they perform. For example, the large amount of 
 elastic tissue in the wall of the aorta and other large arteries tends to main- 
 tain a uniform diameter in these vessels against the force exerted by the 
 blood expelled from the heart at each contraction. 
 
 The Heart. The heart has a peculiar origin in that it arises as two sep- 
 arate parts or anlagen which unite secondarily. In the chick, for example, 
 it appears during the first day of incubation, at a time when the germ layers 
 are still flat. The coelom in the cephalic region becomes dilated to form the 
 so-called primitive pericardial cavity (parietal cavity), and at the same time 
 a space appears on each side, not far from the medial line, in the mesodermal 
 layer of the splanchnopleure (Fig. 203) . These spaces at first are filled with 
 a gelatinous substance in which lie a few isolated cells. These cells then 
 take on the appearance of endothelium and line the cavities, and the meso- 
 thelium in this vicinity is changed into a distinct, thickened layer of cells. 
 Now by a bending ventrally of the splanchnopleure the cavities or vessels 
 are carried toward the midventral line (Fig. 203). The bending continues 
 until the entoderm of each side meets and fuses with that of the opposite 
 side, thus closing in a flat cavity the fore-gut. The entoderm ventral 
 to the cavity breaks away and allows the medial walls of the two endothelial 
 tubes to come in contact. These walls then break away and the tubes are 
 united in the midventral line to form a single tube (Fig. 203), which extends 
 longitudinally for some distance in the cervical region of the embryo. The 
 mesothelial layers of opposite sides meet dorsal and ventral to the endo- 
 thelial tube, forming the dorsal and ventral mesocardium (Fig. 203). In 
 the meantime the cephalic end of the tube has united with the arterial system, 
 and the caudal end with the venous system ; and in a short time the dorsal 
 and ventral mesocardia disappear and leave the heart suspended by its 
 two ends in the primitive pericardial cavity. The conditions at this point 
 may be summarized thus: The heart is a double-walled tube the inner wall 
 composed of endothelium and destined to become the endocardium, the 
 
228 
 
 TEXT-BOOK OF EMBRYOLOGY 
 
 outer wall of a thicker mesothelial layer and destined to become the myo- 
 cardium the two walls separated by a considerable space. The organ 
 hangs, as it were, in the primitive pericardial cavity (ccelom), connected 
 
 Dors, ryesocardiuy 
 sotr/ elluiy) 
 
 Priry, 
 
 fieri ca. ret,. 
 
 Cavity 
 
 FIG. 203. Diagrams showing the two anlagen of the heart and their union to form a single 
 structure; made from camera lucida tracings of transverse sections of chick embryos. 
 In C the ventral mesocardium has disappeared (see text). 
 
 at its cephalic end with the ventral aortic trunk and at its caudal end with 
 the omphalomesenteric veins. 
 
 In all Mammals thus far studied the principle of development in the 
 earlier stages is essentially the same as in the chick. The double origin 
 of the heart is even more marked because of the relatively late closure of 
 
THE DEVELOPMENT OF THE VASCULAR SYSTEM 
 
 229 
 
 the fore-gut. There are no observations on the origin of the heart in human 
 embryos, but it is reasonable to assume that it has the same double origin 
 
 Dorsal aortic root 
 
 Gut (pharynx) 
 
 Pericardial 
 cavity (ccelom) 
 
 Endocardium 
 (endothelium) 
 
 Myocardium 
 
 FIG. 204. Transverse section of a human embryo of 2.69 mm. von Spee, Kollmann's Atlas. 
 
 Oral fossa 
 
 Ventral aortic, 
 
 trunk" " 
 
 Ventricle 4 
 
 Ant. cardinal vein 
 Duct of Cuvier 
 Umbilical vein 
 
 Ventricle 
 
 Atrium 
 
 Diaphragm 
 
 Duct of Cuvier 
 
 Liver 
 
 Duct of liver 
 
 FIG. 205. Ventral view of reconstruction of human embryo of 2.15 mm. His. 
 
 The ventral body wall has been removed. The vessels (in black) at the sides of the duct 
 
 of the liver are the omphalomesenteric veins. 
 
 as in other Mammals, although in embryos of 2 to 3 mm. the organ has 
 already become a single tube (Figs. 204 and 205). At this stage the tube is 
 somewhat coiled. 
 
230 
 
 TEXT-BOOK OF EMBRYOLOGY 
 
 While the double origin of the heart is characteristic of all amniotic Vertebrates 
 (Reptiles, Birds, Mammals), in all the lower forms the organ arises as a single anlage. In 
 the region of the fore-gut the two halves of the coelom are separated by a ventral mesentery 
 which extends from the gut to the ventral body wall, and which is composed of two layers 
 of mesothelium with a small amount of mesenchyme between them. In the mesenchyme 
 a cavity appears and is lined by a single layer of flat (endothelial) cells. This cavity 
 extends longitudinally for some distance in the cervical region and with its endothelial 
 and mesothelial walls constitutes the simple cylindrical heart. On the dorsal side it is 
 connected with the gut by a portion of the mesentery which is called the dorsal meso- 
 cardium; on the ventral side it is connected with the ventral body wall by the ventral 
 mesocardium (Fig. 206). Thus the heart is primarily a single structure. The difference 
 between the two types of development is not a fundamental one but simply depends upon 
 the difference in the germ layers. In the lower forms the germ layers are closed in ven- 
 
 Entoderm 
 Mesoderm (visceral) 
 
 Heart 
 
 Pericard. cavity 
 (ccelom) 
 
 Dorsal mesocardium 
 
 Endothelium 
 Mesoderm (parietal) 
 Ventral mesocardium 
 Ectoderm 
 
 FIG. 206. Ventral part of transverse section through the heart region of Salamandra 
 maculosa embryo with 4 branchial arches. RabL 
 
 trally from the beginning, and the heart appears in a medial position. In the higher 
 forms the germ layers for a time remain spread out upon the surface of the yolk or yolk 
 sac, and the heart begins to develop before they close in on the ventral side of the embryo. 
 Consequently the heart arises in two parts which are carried ventrally by the germ layers 
 and unite secondarily. 
 
 The further development of the heart consists of various changes in the 
 shape of the tube and in the structure of its walls. At the same time the dila- 
 tation of the coelom (primitive pericardial cavity) in the cervical region is of 
 importance in affording room for the heart to grow. In the chick, for ex- 
 ample, the tube begins, toward the end of the first day of incubation, to 
 bend to the right; during the second day it continues to bend and assumes 
 an irregular S-shape. This bending process has not been observed in 
 human embryos, but other Mammals show the same process as the chick. 
 In a human embryo of 2.15 mm. the S-shaped heart is present (Fig. 205). 
 The venous end, into which the omphalomesenteric veins open, is situated 
 somewhat to the left, extends cranially a short distance and then passes 
 over into the ventricular portion. The latter turns ventrally and extends 
 obliquely across to the right side, then bends dorsally and cranially to join 
 the aortic bulb which in turn joins the ventral aortic trunk in the medial 
 
THE DEVELOPMENT OF THE VASCULAR SYSTEM 231 
 
 line. The endothelial tube, which is still separated from the muscular wall 
 by a considerable space, becomes somewhat constricted at its junction with 
 the aortic bulb to form the so-called f return Halleri. During these changes 
 the heart as a whole increases in diameter, especially the ventricular portion. 
 Gradually the venous end of the heart moves cranially and in embryos of 
 
 Vent, aortic tmnlr 
 
 FIG. 207. Ventral view heart of human embryo of 4.2 mm. His. 
 The atria are hidden behind the ventricular portion. 
 
 4.2 mm. lies in the same transverse plane as the ventricular portion. The 
 latter lies transversely across the body (Fig. 207). At the same time two 
 evaginations appear on the venous end, which represent the anlagen of the 
 atria. In embryos of about 5 mm. further changes have occurred, which are 
 represented in Fig. 208. The two atrial anlagen are larger than in the 
 
 Right atrium [M .: JH "^KSfc* Left atrium 
 
 Right ventricle '({.' Left ventricle 
 
 Interventricular furrow 
 FIG. 208. Ventral view of heart of human embryo of 5 mm. His. 
 
 preceding stage and surround, to a certain extent, the proximal end of the 
 aortic trunk. As they enlarge still more in later stages, they come in con- 
 tact, their medial walls almost entirely disappear, and they form a single 
 chamber. The ventricular portion of the heart becomes separated into a 
 right and a left part by the interventricular furrow (Fig. 208) ; the right part 
 
232 
 
 TEXT-BOOK OF EMBRYOLOGY 
 
 is the anlage of the right ventricle, the left part, of the left ventricle. At the 
 same time the atrial portion has moved still farther cranially so that it lies 
 to the cranial side of the ventricular portion. The venous and arterial 
 ends of the heart have thus reversed their original relative positions. At 
 this point it should be noted that the atrial end of the heart is connected 
 with the large venous trunk formed by the union of the omphalomesenteric 
 veins and the ducts of Cuvier the sinus venosus. 
 
 During the changes in the heart as a whole, certain changes also occur in 
 the endothelial and muscular walls. The walls of the atria are composed 
 of compact plates of muscle with the endothelium closely investing the inner 
 surface. The walls of the ventricular portion, on the other hand, become 
 thicker and are composed of an outer compact layer of muscle and an inner 
 layer made up of trabeculcc which are closely invested by the endothelium. 
 
 Septum spurium 
 
 Atrial septum 
 (septum superius) 
 
 Opening of sinus venosus 
 
 Right atrium 
 Left atrium 
 Atrio-ventricular canal 
 
 Right ventricle 
 Ventricular septum 
 Left ventricle 
 
 FIG. 209. Dorsal half of heart (seen from ventral side) of a human embryo of 10 mm. His. 
 
 Everywhere the endothelium is closely applied to the inner surface of the 
 myocardium, the space which originally existed between the endothelium 
 and mesothelium being obliterated. 
 
 The embryonic heart in Mammals in the earlier stages resembles that of the adult in 
 the lower Vertebrates (Fishes). The atrial portion receives the blood from the body veins 
 and conveys it to the ventricular portion which in turn sends it out through the arteries 
 to the body. The circulation is a single one. This condition changes during the fcetal 
 life of Mammals with the development of the lungs. The same transition occurs in the 
 ascending scale of development in the vertebrate series in those forms in which gill breath- 
 ing is replaced by lung breathing. The change consists of a division of the heart and 
 circulation, so that the single circulation becomes a double circulation. In other words, 
 the heart is so divided that the lung (pulmonary) circulation is separated from the 
 general circulation of the body. This division first appears in the Dipnoi (Lung Fishes) 
 and Amphibians in which gill breathing stops and lung breathing begins, although here 
 
THE DEVELOPMENT OF THE VASCULAR SYSTEM 
 
 233 
 
 the division is not complete. In Reptiles the division is complete except for a small 
 direct communication between the ventricles. 
 
 Fig. 209 represents the dorsal half of the heart at a stage when all the 
 chambers are in open communication, and shows the conditions in a single 
 circulation but with the beginning of a separation. The atria are rather 
 thin- walled chambers, the ventricles have relatively thick walls. Between 
 the atrial and ventricular portion is a canal the atrio-ventricular canal 
 which affords a free passage for the blood. From the cephalic side of the 
 atrial portion a ridge projects into the cavity. This ridge represents a 
 remnant of the original medial walls of the two atria and marks the begin- 
 ning of the future atrial septum. The opening of the sinus venosus is seen 
 on the dorsal wall of the right atrium. Primarily both atria communicated 
 
 Septum superius " 
 Sinus venosus 
 
 Valvulse venossc 
 Right atrium -- 
 
 Right ventricle / 
 
 Ventricular septum . 
 
 FIG. 210. Dorsal half of heart showing chambers and septa. 
 
 Modified from Born. 
 
 Foramen ovale 
 
 Atrial septum 
 
 Left atrium 
 
 Atrio-ventricular valves 
 
 _ Atrio-ventricular canals 
 Left ventricle 
 
 (Semidiagrammatic.) 
 
 directly with the sinus venosus,but in the course of development the open- 
 ing of the latter migrated to the right and at this stage is found in the wall 
 of the right atrium. The opening is guarded, as it were, by a lateral and a 
 medial fold the significance of which will be described later. The vetricular 
 portion also shows a ridge projecting from the caudal side, which corresponds 
 to the interventricular groove and represents the beginning of the ventricular 
 septum. 
 
 The Septa. The further changes are largely concerned with the separa- 
 tion of the heart into right and left sides, and with the development of the 
 valves. The atria become separated by the further growth on the cephalic 
 side, of the ridge which has already been mentioned and which is known as 
 the septum superius (Figs. 209 and 210). This septum grows across the 
 cavity of the atria until it almost reaches the atrio-ventricular canal, form- 
 ing the septum atriorum. A portion of the septum then breaks away, leav- 
 ing the two atria still in communication. This secondary opening is the 
 
234 
 
 TEXT-BOOK OF EMBRYOLOGY 
 
 foramen ovale which persists throughout foetal life, but closes soon after 
 birth. The atrio-ventricular canal also becomes divided into two passages 
 
 Sinus venosus 
 Left valvula venosa 
 Right valvula venosa 
 
 Right ventricle ~~! 
 
 Right atrio- 
 ventricular canal 
 
 Right ventricle 
 
 Atrial septum 
 
 Pulmonary vein 
 
 Left atrium 
 
 Left atrio- 
 ventricular canal 
 
 Left ventricle 
 
 Interventricular furrow Ventricular septum 
 
 FIG. 211. Dorsal half of heart (ventral view) of rabbit embryo of 5.8 mm. Born. 
 
 by a ridge from the dorsal w.all and one from the ventral wall uniting with 
 each other and finally with the septum atriorum (Fig. 210). Thus the two 
 atria would be completely separated if it were not for the foramen ovale. 
 
 Aorta 
 
 Aortic septum 
 
 Interventricular opening .;/_ 
 
 Right atrio-ventricu- 
 lar orifice 
 
 Right ventricle 
 Ventricular septum 
 
 Pulmonary artery 
 
 Aorta 
 
 Left atrio-ventricular orifice 
 
 - Left ventricle 
 
 FIG. 212. Ventricles and proximal ends of aorta and pulmonary artery of a 7.5 mm. human 
 embryo. Lower walls of ventricles have been removed. Kollmann's Atlas. 
 
 During the separation of the atria, a division of the ventricular portion 
 of the heart also occurs. On the caudal side of the ventricular portion a 
 
THE DEVELOPMENT OF THE VASCULAR SYSTEM 235 
 
 septum appears and gradually grows across the cavity forming the septum 
 ventriculorum (Figs. 209 and 210). This septum is situated nearer the right 
 side and is indicated on the outer surface by a groove which becomes the 
 sulcus longitudinalis anterior and posterior. The dorsal edge of this septum 
 finally fuses with the septum dividing the atrio-ventricular canal, but for a 
 time its ventral edge remains free, leaving an opening between the two 
 ventricles (Figs. 211 and 212). 
 
 This opening then becomes closed in connection with the division of the 
 aortic bulb and ventral aortic trunk. On the inner surface of the aortic 
 trunk, at a point where the branches which form the pulmonary arteries 
 arise, two ridges appear, grow across the lumen and fuse with each other, 
 thus dividing the vessel into two channels. This partition the septum 
 aorticum (Fig. 213) gradually grows toward the heart through the aortic 
 bulb and finally unites with the ventral edge of the ventricular septum, thus 
 closing the opening between the two ventricles. Corresponding with the 
 
 FIG. 213. Diagrams representing the division of the ventral aortic trunk into aorta and 
 pulmonary artery- and the development of the semilunar valves. Hochstetter. 
 
 edges of the septum aorticum, a groove appears on each side of the aortic 
 trunk and gradually grows deeper and extends toward the heart, until finally 
 the trunk and aortic bulb are split longitudinally into two distinct vessels, 
 one of which is connected with the right ventricle and becomes the pulmonary 
 artery, the other with the left ventricle and becomes the proximal part of the 
 aortic arch (Fig. 212). The result of the formation of these various septa is 
 the division of the entire heart into two sides. The atrium and ventricle 
 of each side are in communication through the atrio-ventricular foramen, the 
 two sides are in communication only by the foramen ovale which is but a 
 temporary opening. 
 
 After the opening of the sinus venosus is shifted to the right atrium, the 
 left atrium for a short period has no vessels opening into it. As soon, how- 
 ever, as the pulmonary veins develop, they form a permanent union with the 
 left atrium (Fig. 211). At first two veins arise from each lung, which unite 
 to form a single vessel on each side; the two single vessels then unite to form 
 a common trunk which opens into the left atrium on the cephalic side. As 
 
236 TEXT-BOOK OF EMBRYOLOGY 
 
 development proceeds, the wall of the single trunk is gradually absorbed in 
 the wall of the atrium, until the single vessel from each side opens separately. 
 Absorption continuing, all four veins, two from each lung finally open 
 separately. This is the condition usually found in the adult. A partial 
 failure in the absorption may leave one, two, or three vessels opening into 
 the atrium. Such variations are not infrequently met with in the pulmonary 
 veins. 
 
 The Valves. If all the passageways between the different chambers of 
 the heart and the large vascular trunks were to remain free and clear, there 
 would be nothing to prevent the blood from flowing contrary to its proper 
 course. Consequently five sets of valves develop in relation to these orifices, 
 and are so arranged that they direct the blood in a certain definite direction. 
 These appear (a) at the openings of the large venous trunks into the right 
 atrium, (b) at the opening between the right atrium and right ventricle, 
 (c) at the opening between the left atrium and left ventricle, (d) at the 
 opening between right ventricle and pulmonary artery and (e) at the open- 
 ing between the left ventricle and aorta. No valves develop at the openings 
 of the pulmonary veins into the left atrium. 
 
 (a) The sinus venosus (which is formed by the union of the large body 
 veins) opens into the right atrium on its cranial side, as has already been 
 mentioned (p. 232). By a process of absorption, similar to that in the case 
 of the pulmonary veins, the wall of the sinus is taken up into the wall of the 
 atrium. The result is that the vena cava superior, vena cava inferior, and 
 sinus coronarius (a remnant of the left duct of Cuvier) open separately into 
 the atrium. As the sinus is absorbed, its wall forms two ridges on the 
 inner surface of the atrium, one situated at the right of the opening and one 
 at the left (Figs. 210 and 211). These two ridges valvulcz venosce are 
 united at their cranial ends with the septum spurium (Fig. 209), a ridge 
 projecting from the cephalic wall of the atrium. The septum spurium 
 probably has a tendency to draw the two valves together and prevent the 
 blood from flowing back into the veins. The left valve and the septum 
 spurium later atrophy to a certain extent and probably unite with the septum 
 atriorum to form part of the limbus fosses ovalis (Vieussenii) . The right 
 valve is the larger and in addition to its assistance in preventing a backward 
 flow of blood into the veins, it also serves to direct the flow toward the 
 foramen ovale. As the veins come to open separately, the cephalic part 
 of the right valve disappears; the greater part of the remainder becomes 
 the valvula vence cavcz inferioris (Eustachii) and during foetal life directs the 
 blood toward the foramen ovale. In the adult it becomes a structure of 
 variable size. A small part of the remainder of the right valve forms the val- 
 vula sinus coronarii (Thebesii) which guards the opening of the coronary sinus. 
 
THE DEVELOPMENT OF THE VASCULAR SYSTEM 237 
 
 (b) and (c) The valves between the atrium and ventricle on each side 
 develop for the most part from the walls of the triangular atrio-ventricular 
 opening (ostium atrio-ventriculare) . Elevations or folds appear on the rims 
 of the openings and project into the cavities of the ventricles where they 
 become attached to the muscle trabeculas of the ventricle walls (Figs. 214 
 and 215). On the right side three of these folds appear, and develop into the 
 vahula tricuspidalis which guards the right atrio-ventricular orifice. On 
 the left side only two folds appear, and these become the valvula biscuspidalis 
 (mitralis) which guards the left atrio-ventricular orifice. These valves, 
 which are at first muscular, soon change into dense connective tissue. The 
 muscle trabeculae to which they are attached also undergo marked changes. 
 Some become condensed at the ends which are attached to the valves into 
 slender tendinous cords the chorda tendinece, while at their opposite ends 
 
 Muscle trabeculae 
 
 Trabeculae carneae 
 
 FIG. 214. Diagrams representing the development of the atrio-ventricular valves, chordae, 
 tendinese, and papillary muscles. Gcgcnbaur. 
 
 they remain muscular as the Mm. papillares; others remain muscular and 
 lie in transverse planes in the ventricles, or fuse with the more compact 
 part of the muscular wall, or form irregular, anastomosing bands and con- 
 stitute the trabecula carnea (Fig. 214). 
 
 (d) and (e) The valves of the pulmonary artery and aorta develop at the 
 point where originally the endothelial tube was constricted to form the 
 f return Halleri (p. 231) where the ventricular portion of the heart joined 
 the aortic bulb. Before the aortic trunk and bulb are divided into the aortic 
 arch and pulmonary artery, four protuberances appear in the lumen (Fig. 
 213). The septum aorticum then divides the two which are opposite so that 
 each vessel receives three (Fig. 213). These then become concave on the 
 side away from the heart, in a manner which has not been fully determined, 
 and at the same time enlarge so that they close the lumen. Those in the 
 pulmonary artery are known as the valvula semilunares arterice pulmonalis, 
 those in the aorta as the valvula semilunares aorta. 
 
 Changes after Birth. The migratory changes of the heart from its origi- 
 nal position in the cervical region to its final position in the thorax will be con- 
 
238 
 
 TEXT-BOOK OF EMBRYOLOGY 
 
 sidered in connection with the development of the pericardium (Chap. XIV). 
 With the exception of the septum atriorum, the heart acquires during foetal 
 life practically the form and structure characteristic of the adult (Fig. 
 216). So long as the individual continues to grow, the heart, generally 
 speaking, increases in size accordingly. This increase takes place by in- 
 tussusception in the endocardium and myocardium. At the time of birth 
 the two atria are in communication through the foramen ovale which is 
 
 Dorsal aortic roots 
 
 Amnion 
 
 Upper limb bud 
 
 Atrial septum 
 
 Right atrium 
 
 Right atrio- 
 
 ventricular 
 
 (tricuspid) valves 
 
 Right ventricle 
 
 Pericardial cavity 
 
 Left atrium 
 
 Left atrio- 
 ventricular 
 (bicuspid) valves 
 
 Left ventricle 
 
 FIG. 215. Transverse section of pig embryo of 14 mm. Photograph. 
 
 simply an orifice in the atrial septum (Fig. 217). Thus the blood which is 
 brought to the right atrium by the body veins is allowed to pass directly 
 into the left atrium, thence to the left ventricle, and thence is forced out to 
 the body again through the aorta. A certain amount of blood also passes 
 from the right atrium into the right ventricle and thence into the pulmonary 
 artery; but this blood does not enter the lungs but passes directly into the 
 aorta through the ductus arteriosus (Fig. 216). After birth the lungs begin 
 
THE DEVELOPMENT OF THE VASCULAR SYSTEM 
 
 239 
 
 Innominate artery 
 
 Branches of right 
 pulmonary artery " 
 
 Arch of aorta 
 Pulmonary artery 
 
 Right auricular appendage- - -j- --- 7 
 
 Left carotid artery 
 Left subclavian artery 
 
 Ductus arteriosus 
 
 Branches of left 
 pulmonary artery 
 
 Left auricular appendage 
 
 --- Left ventricle 
 
 Right ventricle i-_--\- - - 
 
 Descending aorta 
 
 FIG. 216. Ventral view of heart of foetus at term. Kollmann's Atlas. 
 
 Sup. vena cava- 
 
 Inf . vena cava 
 
 Right atrium- 
 
 Right ventricle .- . _ 
 
 Inf. vena cava 
 
 Left ventricle 
 
 FIG. 217. Dorsal half of foetal heart. Bumm, Kollmann's Atlas. 
 
240 
 
 TEXT-BOOK OF EMBRYOLOGY 
 
 to function and the placental blood is cut off, so that the right atrium receives 
 venous blood only and the left arterial blood only. If the foramen ovale were 
 to persist it would allow a mingling of venous and arterial blood. Con- 
 sequently the foramen ovale closes soon after birth and the two currents of 
 blood are completely separated. At the same time the ductus arteriosus 
 atrophies and becomes the ligamentum arteriosum. Consequently there is 
 no direct communication between the pulmonary artery and aorta. 
 
 Certain features of development have an important bearing on the theories regarding 
 the physiology of the heart, particularly on the theory that the heart is an automatic 
 organ. Whether the theory that the heart beats automatically, i.e., independently of 
 stimuli from the nervous system, is true or not, it is a fact that in the embryo it begins to 
 beat before any nerve cells appear in it and before any nerve fibers are connected with it. 
 At least no technic has yet been devised by which it is possible to demonstrate nerve cells 
 in, or fibers connected with it, at the time when it begins to perform its characteristic 
 function. And, furthermore, at the time when the heart begins to beat, no heart muscle 
 cells are developed. This last fact seems to indicate an inherent contractility in the 
 mesothelial cells which form the anlage of the myocardium. 
 
 The Arteries. The simplest condition of the arterial system, following 
 the establishment of the vitelline and allantoic circulation (p. 220 and p. 
 
 Dors, aortic root 
 
 Dors, aortic root 
 
 Vent, aortic root ' ^^ , ^ / ^ , ,^^_ ^ 
 
 (Esophagus 
 
 Vent, aortic trunk "" "^W \ ^^ " Trachea 
 
 \ - - : Pulmonary artery 
 
 FIG. 218. From reconstruction of aortic arches (i, 2, 3, 4, 6) of left side and pharynx 
 
 of a 5 mm. human embryo. Tandler. 
 
 I-IV, Inner branchial grooves. 
 
 222), is as follows: The single ventral aortic trunk is given off from the 
 cephalic end of the heart. This is a short vessel, soon dividing into the 
 two ventral aortic roots which pass forward beneath the pharynx (Fig. 218). 
 Each ventral aortic root gives rise to branches which pass dorsally, one in 
 each branchial arch, as the aortic arches to unite in a common stem along 
 the dorsal wall of the pharynx. This common stem is the dorsal aortic 
 root (Fig. 218) which fuses with its fellow of the opposite side in the mid- 
 dorsal line to form the dorsal aorta. The single dorsal aorta, situated 
 ventral to the notochord, extends from the cervical region to the caudal 
 end of the embryo. Somewhat caudal to the middle of the embryo a branch 
 
THE DEVELOPMENT OF THE VASCULAR SYSTEM 
 
 241 
 
 of the aorta passes ventrally through the mesentery as the vitelline artery 
 which enters the umbilical cord (Fig. 202). Still farther caudally the 
 paired umbilical (allantoic) arteries are given off from the aorta and pass 
 out into the umbilical cord (Fig. 202). 
 
 The conditions which exist at this stage in the region of the aortic arches" 
 in mammalian embryos are indicative of the conditions which persist as a' 
 whole or in part throughout life in the lowest Vertebrates. The changes' 
 which occur in Mammals, however, are profound and the adult condition 
 bears no resemblance to the embryonic. Yet certain features in the adult 
 are intelligible only from a knowledge of their development. In the human ( 
 
 Vent, aortic roots 
 
 Ventral aortic trunk 
 
 Gubclavian arteries 
 
 Aorta 
 
 FIG. 219. Diagram of the aortic arches of a Mammal. Modified from Ilochstettcr. 
 
 embryo six aortic arches appear on each side. The first, second, third, and 
 fourth pass through the corresponding branchial arches. The fifth arch, 
 which is merely a loop from the fourth, seems to pass through the fourth 
 branchial arch. The sixth aortic arch passes through the region behind 
 the fourth branchial. All these arches are present in embryos of 5 mm. 
 (Fig. 218). In Fishes and larval Amphibians, where the branchial arches 
 develop into the gills, the aortic arches are broken up into capillary net- 
 works which ramify in the gills, and the ventral aortic root becomes the 
 afferent vessel, the dorsal aortic roots the efferent vessels. In the higher 
 Vertebrates and in man the aortic arches begin, at a very early period, to 
 
242 
 
 TEXT-BOOK OF EMBRYOLOGY 
 
 undergo changes; some disappear and others become portions of the large 
 arterial trunks which leave the heart. In connection with the following 
 description, constant reference to Figs. 219 and 220 will assist the student in 
 understanding the changes. 
 
 The first and second arches soon atrophy and disappear. The third 
 arch on each side becomes the proximal part of the internal carotid artery, 
 while the continuation of the dorsal aortic root, cranially to the third arch, 
 becomes its more distal part. The continuation of the ventral aortic root 
 cranially to the third arch, becomes the proximal part of the external carotid 
 
 Common carotid arteries 
 
 Int. carotid artery (right) 
 Ext. carotid artery (right) 
 
 n , 
 
 Int. carotid III 
 
 Subclavian IV 
 
 V 
 
 VI 
 
 Innominate artery 
 
 Subclavian artery (right) 
 
 Int. carotid artery (left) 
 
 Ext. carotid artery (left) 
 
 II 
 
 III Int. carotid 
 ' IV Arch of aorta 
 V 
 
 VI Ductus arteriosus 
 
 Pulmonary artery 
 Subclavian artery (left) 
 Aorta 
 
 FIG. 220. Diagram representing the changes in the aortic arches of a Mammal. 
 Compare with Fig. 219. Modified from Hochstetter. 
 
 artery, while the portion of the ventral aortic root between the third and 
 fourth arches becomes the common carotid artery. The portion of the dorsal 
 aortic root between the third and fourth arches disappears. The fourth 
 aortic arch on the left side enlarges and becomes the arch of the aorta (arcus 
 aorta) which is then continued caudally through the left dorsal aortic root 
 into the dorsal aorta. On the right side, the fourth arch becomes the proxi- 
 mal part of the Subclavian artery. Since the third, fourth, fifth, and sixth 
 arches really leave the ventral aortic trunk as a single vessel, it will be seen 
 that these changes bring it about that the common carotid and subclavian 
 
THE DEVELOPMENT OF THE VASCULAR SYSTEM 243 
 
 on the right side arise by a common stem, the innominate artery, which in 
 turn is a branch of the arch of the aorta. On the left side, for the same 
 reason, the common carotid is a branch of the arch of the aorta. The fifth 
 aortic arch from the beginning is rudimentary and disappears very early. 
 The sixth arch on each side undergoes wide changes. A branch from each 
 enters the corresponding lung. On the right side the portion of the sixth 
 arch between the branch which enters the lung and the dorsal aortic root 
 disappears, as does also that portion of the right dorsal aortic root between 
 the subclavian artery and the original bifurcation of the dorsal aorta. On 
 the left side, however, that portion of the sixth arch between the branch 
 which enters the lung and the dorsal aortic root persists until birth as the 
 ductus arleriosiis (Botalli). This conveys the blood from the right ventricle 
 to the aorta until the lungs become functional (Fig. 216); it then atrophies 
 
 Int. carotid artery 
 
 Vertebral artery 
 
 Segmental cervical artery 
 
 ^' r Pulmonary artery 
 
 FIG. 221. Diagram cf the aortic arches (III, IV, VI) and segmented cervical arteries 
 cf a 10 mm. human embryo. His. 
 
 and becomes the ligamentum arteriosum. In the meantime the septum 
 aorticum has divided the original ventral aortic trunk into two vessels (see 
 P- 2 35)j one of the vessels communicates with the left ventricle and is the 
 proximal part of the arch of the aorta, the other communicates with the right 
 ventricle and becomes the large pulmonary artery (Fig. 212). 
 
 In human embryos of 10 mm. the dorsal aortic root on each side gives off 
 several lateral branches the segmental cervical vessels (Fig. 221). The 
 first of these (first cervical, suboccipital), which arises nearly opposite the 
 fourth aortic arch, is a companion, as it were, to the hypoglossal nerve, and 
 sends a branch cranially which unites with its fellow of the opposite side in- 
 side the skull to form the basilar artery. The basilar artery again bifurcates 
 and each branch unites with the corresponding internal carotid by means of 
 the circulus arteriosus (Fig. 223). The other segmental cervical vessels 
 arise from the aortic root at intervals, the eighth arising near the point of 
 
244 
 
 TEXT-BOOK OF EMBRYOLOGY 
 
 bifurcation of the aorta. In a short time a longitudinal anastomosis appears 
 between these segmental arteries, which extends as far as the seventh (Fig. 
 222). The proximal ends of the first six disappear, and the longitudinal 
 
 r. carotid 
 xt carotid 
 
 -Sub. inter- 
 art. 
 
 FIG. 222. Diagram illustrating the formation of the vertebral and superior intercostal arteries. 
 The broken lines represent the portions of the original segmental vessels that disappear. 
 Modified from Hochstetter. 
 
 vessel forms the vertebral artery which then opens into the aortic root through 
 the seventh segmental artery, and which is continued cranially as the 
 basilar artery (Fig. 223). The seventh (it is held by some to be the sixth) 
 
 Circulus arteriosus 
 
 Middle cerebral 
 artery 
 
 Basilar artery 
 Int. carotid artery 
 
 FIG. 223. Brain and arteries of a human embrvo of o mm. Matt. 
 
 segmental artery becomes the subclavian, and consequently the vertebral 
 opens into the subclavian, as in the adult (Fig. 222). But it should be 
 borne in mind that the right subclavian artery is more than equivalent to 
 the left, since the proximal part of the former is made up of the fourth 
 
THE DEVELOPMENT OF THE VASCULAR SYSTEM 
 
 245 
 
 aortic arch and a part of the aortic root (see Figs. 219 and 220). Further- 
 more, changes occur in the position of the heart during development, which 
 alter the relations of the vessels. The heart migrates from its original 
 position in the cervical region into the thorax, and this produces an elonga- 
 tion of the carotid arteries and an apparent shortening of the arch of the 
 aorta; consequently the subclavian artery on the left side arises relatively 
 nearer the heart. 
 
 The arteries of the brain arise as branches of the internal carotid and circu- 
 lus arteriosus. The anterior cerebral artery and the middle cerebral artery 
 arise primarily from a common stem which in turn is a branch of the most 
 cranial part of the internal carotid (Figs. 223 and 224). The posterior 
 cerebral artery arises as a branch of the circulus arteriosus (Fig. 224). 
 
 Post, cerebral vein 
 (sup. petrosal sinus) 
 
 irculus arteriosus 
 Transverse sinus 
 
 Basilar artery 
 Int. jugular vein 
 
 Confluence of sinuses 
 
 Inf. sagittal sinus 
 Sup. sagittal sinus 
 Post, cerebral artery 
 
 Ant. cerebral artery 
 Int. carotid artery 
 
 FIG. 224. Brain, arteries and veins of a human embryo of 23 mm. Mali 
 
 From the point of its bifurcation to its caudal end the aorta gives off 
 paired, segmental branches which accompany the segmental nerves. The 
 last (eighth) cervical branch and the first two thoracic branches undergo 
 longitudinal anastomoses, similar to those between the first seven cervical, 
 to form the superior intercostal artery (A. intercostalis suprema) which opens 
 into the subclavian (Fig. 222). The other thoracic branches persist as the 
 intercostal arteries; the lumbar branches persist as the lumbar arteries. At 
 the same time anastomoses are formed between the distal ends of the inter- 
 costal and lumbar arteries in the ventro-lateral region of the body wall, 
 which give rise, on the one hand, to the internal mammary artery and, on 
 the other hand, to the inferior epigastric artery. Of these two the former 
 opens into the subclavian, the latter into the external iliac. By a further 
 anastomosis the distal ends of the internal mammary and inferior epigastric 
 are joined, thus forming a continuous vessel from the subclavian to the 
 external iliac (Fig. 225). It is interesting to note that while originally all 
 the lateral branches of the aorta are arranged segmentally, many of them 
 
246 
 
 TEXT-BOOK OF EMBRYOLOGY 
 
 lose their segmental character and are replaced or supplemented by longi- 
 tudinal vessels. 
 
 In addition to the dorsal segmental branches of the aorta, which have 
 been described, other branches develop which carry blood to the viscera. 
 A number of these, or possibly all, are also primarily segmental vessels, 
 although they lose every trace of their segmental character during develop- 
 ment. The first of the visceral branches to appear is the omphalomesenteric 
 artery which arises from the ventral side of the aorta and which has been 
 mentioned in connection with the vitelline circulation. Originally it passes 
 
 Int. mammary artery 
 
 Inf. epigastric artery 
 
 Umbilical artery 
 
 Femoral artery 
 
 FIG. 225. Diagram of human embryo of 13 mm., showing the mode of development 
 of the internal mammary and inferior epigastric arteries. Mall. 
 
 out through the mesentery and follows the yolk stalk to ramify on the surface 
 of the yolk sac. But since the yolk sac is of slight importance, the distal 
 part of the artery soon disappears, while the proximal part becomes the 
 superior mesenteric artery (Fig. 226) . The codiac artery arises from the ventral 
 side of the aorta a short distance cranially to the omphalomesenteric (Fig. 
 226) and gives rise in turn to the gastric, hepatic and splenic arteries. The 
 inferior mesenteric artery also arises from the ventral side of the aorta some 
 distance caudal to the omphalomesenteric (Fig. 226). In the early stages 
 these visceral arteries arise relatively much farther cranially than in the 
 
THE DEVELOPMENT OF THE VASCULAR SYSTEM 
 
 247 
 
 adult. During development they gradually migrate caudally to their normal 
 positions. 
 
 Other branches of the aorta develop in connection with the urinary and 
 genital organs. Several lateral branches supply the mesonephroi, but when 
 the latter atrophy and disappear the vessels also disappear. A periaortic 
 plexus of vessels, with many branches from the aorta, supplies the develop- 
 ing kidneys until these organs reach their definitive position, when one of 
 the branches on each side enlarges to become the renal artery. The de- 
 veloping genital glands are likewise supplied by several branches from the 
 aorta. Later the majority of these vessels disappear, one pair only per- 
 sisting as the internal spermatic arteries which differ in accordance with the 
 
 Coeliac artery 
 
 Sup. mesenteric 
 (vitelline) artery 
 
 Umbilical artery 
 
 Aorta 
 
 Duodenum 
 
 Inf. mesenteric artery 
 Int. iliac artery 
 
 FIG. 226. Diagram of the visceral arteries in a human embryo of 12.5 mm. Tandler. 
 Numerals indicate segmental arteries. 
 
 sex of the individual. In both sexes they are at first very short; in the 
 female, as the ovaries move farther into the pelvic region, they become 
 considerably elongated to form the ovarian arteries; in the male, with the 
 descent of the testes, they become very much elongated to form the testicular 
 arteries. 
 
 The fifth (or fourth?) pair of segmental lumbar arteries primarily gives 
 rise to the vessels which supply the lower extremities, viz., the iliac arteries. 
 These then would be serially homologous to the subclavians. But certain 
 changes occur in this region, which are due to the relations of the umbilical 
 arteries. The latter, as has already been noted, arise as paired branches of 
 the aorta in the lumbar region, pass ventrally through the genital cord 
 (Chap. XV) and then follow the allantois (urachus) to the umbilical cord. 
 
248 TEXT-BOOK OF EMBRYOLOGY 
 
 During foetal life they carry all the blood that passes to the placenta. At an 
 early period a branch from each iliac artery anastomoses with the corre- 
 sponding umbilical, and the portion of the umbilical artery between the 
 aorta and the anastomosis then disappears. This makes the umbilical 
 artery a branch of the iliac; and the blood then passes from the aorta into 
 the proximal part of the liiac which becomes the common iliac artery of the 
 adult. At birth, when the umbilical cord is cut, the umbilical arteries no 
 longer carry blood to the placenta, and their intraembryonic portions, 
 often called the hypogastric arteries, persist only in part; their proximal 
 ends persist as the superior vesical arteries, while the portions which accom- 
 panied the urachus degenerate to form the lateral umbilical ligaments. 
 
 So far as a complete history of the growth of the arteries of the extremities 
 is concerned, knowledge is lacking. The facts of comparative anatomy and 
 the anomalies which occur in the human body have led to certain conclusions 
 which have been largely confirmed by embryological observations; but much 
 more work on the development of the arteries is yet necessary to complete 
 their history. The extremities represent outgrowths from several segments 
 of" the body, the nerve supply is derived from several segments, and the 
 limb buds are likewise primarily supplied by plexuses of vessels arising from 
 several branches of the aorta. In the upper extremity the subclavian, which 
 represents the seventh cervical branch of the aortic root, is the single vessel 
 which eventually develops out of the original plexus. In the lower extremity 
 the common iliac, which represents the fifth lumbar branch of the aorta, 
 is the single vessel which develops out of the plexus supplying the lower 
 limb bud. 
 
 In the upper extremity the subclavian grows as a single vessel to the wrist 
 and then divides into branches corresponding to the fingers. In the forearm 
 it lies between the radius and ulna. In a short time a branch is given off 
 just distal to the elbow and accompanies the median nerve. As this branch 
 increases, the original vessel in the forearm diminishes to form the -uolar 
 interosseous artery; and at the same time the branch unites again with the 
 lower end of the interosseous, takes up the digital branches and becomes 
 the chief vessel of the forearm at this stage, forming the median artery. 
 Later, however, it diminishes in size as another vessel develops, the ulnar 
 artery, which arises a short distance proximal to the origin of the median and, 
 passing along the ulnar side of the forearm, unites with the median to form 
 the superficial volar arch. From the artery of the arm, which is called the 
 brachial artery, a branch develops about the middle and extends distally 
 along the radial side of the forearm. A little later another branch grows out 
 from the brachial just proximally to the origin of the ulnar and extends across 
 to, and anastomoses with, the first branch. Then the portion of the first 
 
THE DEVELOPMENT OF THE VASCULAR SYSTEM 
 
 249 
 
 branch between its point of origin and the anastomosis atrophies, leaving 
 only a small vessel which goes to the biceps muscle. The second branch 
 and the remaining part of the first branch together form the radial artery 
 (Fig. 227) (McMurrich). 
 
 In the lower extremity the primary artery is a continuation of the common 
 iliac which, in turn, is a branch of the aorta. This primary vessel, the sciatic 
 artery, passes distally as far as the ankle. Below the knee it gives off a short 
 branch which corresponds to the proximal part of the anterior tibial artery. 
 Just above the ankle it gives off another branch which corresponds to the 
 distal part of the anterior tibial. As will be seen, these two parts join at a 
 later period to form a continuous vessel. At this early stage the external 
 
 Brachial artei 1" 
 
 Superficial radia* artery- 
 
 Median artery 
 Interosseous artery 
 
 Ulnar artery y 
 
 A 
 
 Brachial artery 
 
 B 
 
 .... Median artery 
 
 -- Interosseous artery 
 ---- Ulnar artery 
 
 Radial artery 
 
 FIG. 227. Diagrams showing (A) an early and (5) a late stage in the development 
 of the arteries of the upper extremity. McMurrich. 
 
 iliac artery is but a small branch of the common iliac; but it gradually in- 
 creases in size, extends farther distally in the thigh as the femoral artery 
 and unites with the sciatic near the knee. Just proximal to its union with 
 the sciatic it gives off a branch which extends distally along the inner side 
 of the leg to the plantar surface of the foot, where it gives off the digital 
 branches. This vessel is the saphenous artery in the embryo, and disappears 
 in part during further development. From this time on, the femoral and its 
 direct continuation, the popliteal, increase in size; and at the same time the 
 sciatic loses its primary connection and becomes much reduced to form the 
 inferior gluteal artery. The direct continuation of the sciatic in the leg, which 
 is now the direct continuation of the popliteal, becomes reduced to form the 
 
250 
 
 TEXT-BOOK OF EMBRYOLOGY 
 
 peroneal artery. The branch of the original sciatic, which was given off just 
 below the knee, unites with the branch which was given off just above the 
 ankle to form a continuous vessel, the anterior tibial artery. A new branch 
 arises from the proximal portion of the peroneal, extends down the back of 
 the leg, and unites with the distal part of the embryonic saphenous to 
 form the posterior tibial artery. The proximal part of the saphenous then 
 atrophies, leaving but one of the small genu branches of the popliteal (Fig. 
 228) (McMurrich). 
 
 ~~ Sciatic artery 
 "Femoral artery 
 
 
 
 . 
 
 
 I 
 
 
 
 
 
 
 n 
 
 \\ 
 
 
 ( 
 
 
 \ 
 
 
 
 
 
 
 4 
 
 ors. artery of foot ^-'- -11 - - 
 
 ---I 
 
 n 
 
 I 
 
 Popliteal artery 
 
 v Ant. tibial artery 
 
 Peroneal artery 
 
 Post, tibial artery 
 
 FIG. 228. Diagrams showing three stages in the development of the arteries 
 of the lower extremity. McMurrich. 
 
 The Veins. The changes which occur during the development of the 
 venous system are so complicated, and in some cases so varied, that the scope 
 of this book permits only a brief outline of the growth of the more important 
 of the venous trunks. 
 
 Corresponding to the arterial system, the first veins to appear are the 
 omphalomesenteric veins. These vessels, which carry blood from the yolk sac 
 to the heart, arise in the area vasculosa, enter the embryonic body at the sides 
 of the yolk stalk, pass cranially along the intestinal tract, and join the caudal 
 end of the heart (Figs. 198, 200, 202 and 231). Next in point of time to ap- 
 pear are the umbilical veins which carry back to the heart the blood which 
 has been carried to the placenta by the umbilical arteries. These also are 
 paired veins within the embryo, although they form a single trunk in the 
 umbilical cord. They extend cranially on each side through the ventro- 
 lateral part of the body wall and join the duct of Cuvier (see below) in the 
 septum transversum (Figs. 201, 202 and 231). Very soon after the appear- 
 ance of the umbilical veins two other longitudinal vessels develop, one on 
 
THE DEVELOPMENT OF THE VASCULAR SYSTEM 
 
 251 
 
 each side of the aorta. In the cervical region they lie dorsal to the branchial 
 arches and are called the anterior cardinal veins (Figs. 200 and 231). The 
 more caudal parts of the vessels are situated in the region of the developing 
 mesonephros and are called the posterior cardinal veins (Figs. 200 and 231). 
 At a point about opposite the heart the anterior and posterior cardinals on 
 each side unite to form a single vessel, the duct of Cuvier, which turns medially 
 through the septum transversum and opens into the sinus venosus (Figs. 
 200 and 216). Thus three primary sets of veins are formed at a very early 
 stage of development: (i) The omphalomesenteric veins; (2) the umbilical 
 veins; (3) the cardinal veins. 
 
 The veins of the head and neck regions are derivatives of the anterior 
 cardinals. The proximal Darts of these vessels are present in embryos of 
 3.2 mm.; later they extend cranially along the ventro-lateral surface of the 
 
 N.V N.VII N.IX 
 
 Mid. cerebral vein 
 
 Sup. cerebral vein 
 
 Inf. cerebral vein 
 
 Lat. vein of head 
 
 FIG. 229. Veins of the head of a 9 mm. human embryo. Mall. 
 
 brain on the medial side of the roots of the cranial nerves. The position 
 relative to the nerves is only temporary, however, for collaterals arising from 
 the veins pass to the lateral side of the nerves and enlarge to form the main 
 channels. The original channels atrophy except in the region of the trigemi- 
 nal nerves where they still remain on the medial side of the nerves as the 
 forerunners of the cavernous sinuses. The vessel thus formed laterally to the 
 cranial nerves (except the trigeminal) on each side of the brain is known as 
 the lateral vein of the head (vena later alis capitis) (Fig. 229.) The blood is 
 collected from the brain region by small vessels which unite to form three 
 main stems; one of these, the superior cerebral vein, opens into the cranial end 
 of the cavernous sinus; another, the middle cerebral vein, opens into the op- 
 posite end of the cavernous sinus; and the third, the inferior cerebral vein, 
 opens into the lateral vein of the head behind the ear vesicle (Figs. 229 and 
 
252 
 
 TEXT-BOOK OF EMBRYOLOGY 
 
 224). The branches of the superior cerebral vein extend over the cerebral 
 hemispheres and unite with their fellows of the opposite side to form the 
 superior sagittal sinus which lies in the medial line (Figs. 224 and 230). 
 The superior sagittal sinus is at first naturally drained by the superior cere- 
 bral veins; but later, as the cerebral hemispheres enlarge and extend farther 
 toward the mid-brain region, it is carried back and joins the middle cerebral 
 vein; still later, for the same reason, it joins the inferior cerebral vein (Fig. 
 230, A and B). During these later changes the connection between the 
 
 C Ard. yety Sufi. SAf. 
 "Otic vesicle 
 
 MU.cerel). vely Cotft. of stf 
 
 vet? 
 
 Coijft.of si.rj uses 
 
 ^ _. 
 La,t.veip o 
 
 FIG. 230. Diagrams representing four stages in the development of the veins of the 
 head in human embryos. M all. 
 
 superior sagittal sinus and the superior cerebral vein is lost (Fig. 230). The 
 middle cerebral vein becomes the superior petrosal sinus which forms a com- 
 munication between the cavernous sinus and transverse sinus. The trans- 
 verse sinus represents the channel between the superior sagittal sinus and the 
 cranial end of the cardinal vein; or in other words, its cranial portion repre- 
 sents the connection between the superior sagittal sinus and the inferior 
 cerebral vein while its caudal portion represents the inferior cerebral vein 
 itself (Fig. 230, compare C and D). The caudal end of the superior sagittal 
 sinus becomes dilated to form the confluence of the sinuses (confluens 
 
THE DEVELOPMENT OF THE VASCULAR SYSTEM 
 
 253 
 
 si tin urn). From the latter a new vessel grows out to form the straight sinus, 
 and a further growth from the straight sinus forms the large vein of the 
 cerebrum (vein of Galen). The inferior sagittal sinus also represents a new 
 outgrowth at the point of junction of the large vein of the cerebrum and 
 inferior sagittal sinus (Fig. 230, D). During the course of development the 
 lateral vein of the head gradually atrophies and finally disappears, and the 
 inferior petrosal sinus probably represents a new formation which extends 
 from the cavernous sinus to the transverse sinus (Fig. 230, C and D). At 
 
 Ant. cardinal 
 (int. jugular) 
 
 Omphalomesenteric 
 (vitelline) 
 
 Mesonephro; 
 
 Subcardinal 
 
 Iliac 
 
 FIG. 231. Diagram of the venous system of a human embryo of 2.6 mm. 
 Slightly modified from Kollmann's Atlas. 
 
 the point where the inferior petrosal joins the transverse sinus the latter 
 passes out of the skull through the jugular foramen to become the internal 
 jugular vein (anterior cardinal). (Mall.) 
 
 As stated in a preceding paragraph, the anterior cardinal veins extend 
 from the ducts of Cuvier to the head region, passing to the dorsal side of the 
 branchial arches. They are at first paired and symmetrical, but, since the 
 heart is situated in the cervical region, are comparatively short and receive 
 blood from the cervical region through segmental branches which belong only 
 
254 
 
 TEXT-BOOK OF EMBRYOLOGY 
 
 to the most cranial of the cervical segments. The other segmental cervical 
 veins, including the subclavian veins, open at first into the posterior cardinals 
 (Fig. 231). Later, however, as the heart recedes into the thorax the anterior 
 cardinal veins are elongated and the segmental cervical veins, including the 
 subclavians, come to open into them (Fig. 233). The bilateral symmetry is 
 then broken by an anastomosing vessel which extends obliquely across from a 
 point on the left cardinal about opposite the subclavian to a point nearer the 
 heart on the right subclavian (Figs. 232, B, and 233). The portion of the left 
 cardinal cranial to the subclavian becomes the left internal jugular vein which 
 
 Ant. cardinal ...... 
 
 Duct of Cuvier 
 Subclavian 
 
 Inf. vena cava 
 
 Post, cardinal 
 Subcardinal.... 
 
 Hiac. 
 
 Ant. cardinal 
 (int. jugular) 
 
 Ext. jugular 
 
 Subclavian 
 Duct of Cuvier 
 Inf. vena cava 
 ..... Post, cardinal 
 
 Post, cardinal 
 Subcardinal 
 
 ... Iliac 
 
 FIG, 
 
 A B 
 
 232. Diagrams of two stages in the development of the anterior and posterior cardinal veins, 
 the Subcardinal veins (revehent veins of the primitive kidney), and the inferior vena cava. 
 The small branches of the cardinals and subcardinals ramify in the primitive kidneys 
 (mesonephroi). Slightly modified from Ilochstetter. 
 
 communciates with the intracranial sinuses. The anastomosis itself be- 
 comes the left innominate vein. The portion of the left cardinal between the 
 subclavian and the duct of Cuvier, the duct of Cuvier itself, and the left horn 
 of the sinus venosus together form the coronary sinus (Fig. 234). On the 
 right side the more distal part of the cardinal becomes the internal jugular 
 vein; the portion between the subclavian and the anastomosis (left innomi- 
 nate vein) becomes the right innominate vein; and the common stem formed 
 by the latter and the left innominate constitutes the superior vena cava 
 which opens into the right atrium (see p. 236). The external jugular vein 
 on each side appears later than the superior cardinal as an independent 
 
THE DEVELOPMENT OF THE VASCULAR SYSTEM 
 
 255 
 
 vessel which comes to lie parallel to the internal jugular and opens into it 
 near the subclavian. The opening, however, shifts to the subclavian, 
 where it is usually found in the adult (Figs. 323 and 234). 
 
 The changes which occur in the posterior cardinal veins are very extensive 
 and result in conditions which bear but little resemblance to those in the 
 earlier stages. In connection with these changes the development of the 
 inferior vena cava must be considered. The posterior cardinal veins appear 
 very early as paired, bilaterally symmetrical vessels which extend from the 
 duct of Cuvier to the tail region and are situated ventro-lateral to the aorta 
 
 Ant. cardinal 
 (int. jugular) 
 
 Ext. jugular - 
 
 Innominate (right) 
 
 Sup. vena cava - 
 
 Post, cardinal 
 (azygos) - 
 
 Inf. vena cava ... 
 
 Subcardinal 
 
 Subcardinal 
 
 Hiac 
 
 FlG. 233. Diagram representing a stage (later than Fig. 232) in the development of the superior 
 vena cava and the inferior vena cava, also of the azygos vein. Hochstetter. 
 
 (Fig. 231). From the first they receive blood from the body wall through 
 segmental branches, and as the primitive kidneys (mesonephroi) develop 
 they receive blood from them also, as well as from the mesentery. They 
 return practically all the blood from the region of the body situated caudal 
 to the heart, just as the anterior cardinals return the blood from the region 
 of the body situated cranial to the heart. In other words, the two sets of 
 cardinal veins are the body veins par excellence during the earlier stages of 
 development. While the anterior set persists for the most part as permanent 
 vessels and increases with the development of the body, the posterior set 
 
256 TEXT-BOOK OF EMBRYOLOGY 
 
 undergoes regressive changes, its function being taken by a new vessel 
 the inferior vena cava. 
 
 Not long after the appearance of the posterior cardinals, another pair of 
 longitudinal veins appears in the medial part of the mesonephroi. They 
 increase in size as the mesonephroi increase and receive blood from the 
 latter. They also communicate with the cardinals by means of transverse 
 channels which, however, are later broken up as the mesonephroi become 
 more complicated in structure. These vessels are known as the subcardinal 
 veins, or revehent veins of the primitive kidneys (Fig. 232, A). After 
 they have attained a considerable size, a large anastomosis is formed between 
 them ventral to the aorta and just caudal to the omphalomesenteric (superior 
 mesenteric) artery (Fig. 232, B). In the meantime, a branch of the ductus 
 
 Int. jugular 
 (ant. cardinal; J ^ 3 '"'Ext. jugular 
 
 .^^^ v.. Subclavian 
 
 Innominate (right) ^^^ 
 
 _ /-Innominate (left) 
 
 Sup. vena cava***" 
 
 ^^ ^~1 
 
 -Coronary sinus 
 
 Azygos ^ e .. 
 
 ...... *hemiazygos 
 
 (post, cardinal) m , Accessory 
 
 "Ty Hemiazygos 
 
 FIG. 234. Diagram of final stage in the development of the superior vena cava 
 and the azygos vein. (Compare with Fig. 233.) 
 
 venosus (see p. 260) grows caudally through the dorsal part of the liver and 
 the mesentery, and joins the right subcardinal vein a short distance cranial 
 to the above mentioned anastomosis (Fig. 232, A and B). This branch 
 forms the proximal part of the inferior vena cava. At the same time, also, 
 each subcardinal forms a direct connection with the corresponding cardinal 
 at a point opposite the first anastomosis; consequently the inferior vena 
 cava, the subcardinals and the cardinals are all in direct communication 
 (Fig. 232, B). Thus two ways are formed by which the blood may return 
 to the heart: It may return via the cardinals and ducts of Cuvier, and via 
 the inferior vena cava. 
 
 It is obvious that while these conditions exist, that is, while the mesonephros is func- 
 tional, and blood is carried to it by the cardinal veins and from it by the subcardinal veins, 
 there is a true renal portal system. The blood from the body walls and lower extremities 
 
THE DEVELOPMENT OF THE VASCULAR SYSTEM 
 
 257 
 
 is collected by the segmental vessels and poured into the cardinal veins and is then dis- 
 tributed in the mesonephros by smaller channels or sinusoids (Minot), whence it is 
 collected and carried off by the subcardinal veins. This passage of blood through purely 
 venous channels simulates the conditions in the liver where there is a true hepatic portal 
 system. 
 
 From this time on, the changes are largely regressions in the cardinal and 
 subcardinal systems, corresponding to the atrophy of the mesonephroi, and 
 rapid increase in the vena cava and its branches. The cranial end of each 
 cardinal becomes smaller; the left loses its connection with both the vena cava 
 and the duct of Cuvier, the right its connection with the vena cava only (Fig. 
 
 Aorta 
 
 Post, cardinal vein 
 Mesonephric duct' 
 
 Omphalomesenteric artery 
 Right umbilical vei 
 
 Intestine 
 
 Post, cardinal vein 
 
 Dorsal mesentery 
 Ccelom 
 
 Left umbilical vein 
 
 FIG. 235. From a transverse section of a 5 mm. human embryo, at the level of the 
 omphalomesenteric (vitelline, superior mesenteric) artery. 
 
 234;. Subsequent changes in these parts of the cardinals will be considered 
 in the following paragraph. For a time the caudal ends of the two cardinals 
 are of equal importance. Later, however, the right becomes larger, while the 
 left atrophies. The right thus becomes a direct continuation and really a 
 part of the vena cava (Figs. 233 and 236). This is brought about, of course, 
 by the original anastomosis between the vena cava and the subcardinal and 
 cardinal. On the left side the anastomosis persists simply as the proximal 
 part of the renal vein (Fig. 236) ; on the right side the renal vein is a new 
 structure which develops after the kidney has attained practically its final 
 position, and opens into the vena cava secondarily. The inferior vena cava 
 
258 
 
 TEXT-BOOK OF EMBRYOLOGY 
 
 itself is a composite vessel derived from four different anlagen. i. The 
 part which extends from the ductus venosus to the right subcardinal is of 
 independent origin. 2. A short portion is derived from a part of the right 
 subcardinal. 3. Another short portion is derived from the cross-anastomosis 
 between the subcardinals and cardinals. 4. The caudal end is a derivative 
 of the caudal part of the right cardinal (compare Figs. 232, 233, 236.) 
 
 Before the caudal end of the left cardinal vein atrophies, an interesting 
 and important change occurs in the relations of the ureters and cardinals. 
 Primarily the cardinal veins develop to the ventral side of the ureters. But 
 later a collateral of each cardinal develops to the dorsal side of the ureter. 
 These join the cardinal cranial and caudal to the ureter. In other words, a 
 
 Inf. vena cava "" 
 
 Suprarenal gland j'- 
 
 Suprarenal vein (right) 
 
 Renal vein (right) f " 
 
 Int. spermatic (right) 
 Ureter 
 
 Inf. vena cava 
 (right post, cardinal) 
 
 Common iliac (right) , 
 
 _ vena cava 
 
 ,-;X _______ Suprarenal gland 
 
 ._ ---- Suprarenal vein (lefti 
 .*... Kidney 
 
 \- ...... Renal vein (left) 
 
 Int. spermatic"(left) 
 (post, cardinal) 
 
 ^ ..... Ureter 
 
 Common iliac (left) 
 
 ..... Ext. iliac 
 '* Int. iliac 
 
 r?T^ Common iliac (right) 
 ^A B^ 
 
 FIG. 236. Diagrams representing final stages in the development of the inferior vena cava 
 (compare with Fig. 233). Slightly modified from Hochstetter. 
 
 venous loop is formed around the ureter (Fig. 233). The ventral arm of the 
 loop then atrophies and disappears, leaving the dorsal arm as the direct part 
 of the cardinal vein. On the right side, where the cardinal persists as a 
 portion of the vena cava, the latter vessel comes to lie ventral to the ureter 
 (Fig. 236, A). On the left side the cardinal atrophies, leaving only the por- 
 tion cranial to the loop as the proximal end of the internal spermatic (testicular 
 or ovarian ) vein (Fig. 236, B). Since on the left side the original anastomosis 
 between the subcardinals and cardinals persists as the renal vein, the left 
 internal spermatic is a branch of the renal. The right internal spermatic 
 vein probably represents a branch of the vena cava which is independent 
 of the cardinal. 
 
 In the cat embryo the venous loop around the ureter is much more 
 
THE DEVELOPMENT OF THE VASCULAR SYSTEM 
 
 259 
 
 extensive than in the other forms. The dorsal arm of the loop, named the 
 supracardinal vein, extends from the iliac vein to the original anastomosis 
 between the subcardinals and cardinals. In the course of further develop- 
 ment the supracardinals approach each other and finally fuse, forming a 
 large single vessel which becomes the portion of vena cava caudal to the 
 renal veins. In this event the portions of both cardinals forming the ventral 
 arms of the venous loops atrophy and disappear. 
 
 Xear the caudal end of each cardinal vein a branch arises which receives 
 the blood from the corresponding lower extremity. Then a transverse 
 anastomosis appears between the two cardinals at this point (Fig. 236, A). 
 Since the portion of the left cardinal caudal to the renal vein atrophies, the 
 anastomosis itself constitutes the left common iliac vein (Fig. 236, B). The 
 right common iliac is, of course, the original branch of the right cardinal. 
 As the iliacs enlarge they form the two great branches of the vena cava. 
 
 i)uct cf Cuvier.' 
 
 Duct of Cuviet- 
 
 Right umbilical - 
 
 Right omphalomesenteric - 
 
 Ductus venosus 
 
 ..Left umbilical 
 
 Left omphalomesenteric 
 
 FIG. 237. Diagrams illustrating two stages in the transformation of the omphalomesenteric 
 and umbilical veins in the liver. Hochstetter. 
 
 With the atrophy of the mesonephroi, the subcardinal veins diminish in 
 size and finally disappear for the greater part. The part of the right sub- 
 cardinal cranial to the point of junction with the vena cava disappears- 
 entirely. The portion of the left subcardinal cranial to the anastomosis 
 between the two subcardinals becomes much reduced in size, but persists 
 as the left suprarenal vein. The left suprarenal vein is thus a branch of the 
 left renal vein, since the latter represents the anastomosis itself (Figs. 232, 
 2 33? 236). The right suprarenal vein probably does not represent a per- 
 sistent right subcardinal, but is a new vessel opening into the vena cava. 
 The portion of each subcardinal caudal to the anastomosis probably dis- 
 appears entirely, but this has not been definitely determined. 
 
 The observations on the development of the azygos veins in the human 
 embryo are only fragmentary. In the rabbit the portions of the posterior 
 cardinal veins immediately cranial to the anastomosis between the sub- 
 
260 TEXT-BOOK OF EMBRYOLOGY 
 
 cardinals and cardinals, that is, just cranial to the renal veins, disappear. 
 The more cranial portion of the right cardinal persists as the azygos vein 
 which receives the intercostal (segmental) branches and opens into the 
 superior vena cava. An oblique anastomosis is formed, dorsal to the aorta, 
 between the two cardinals (Fig. 233). This anastomosis and the portion of 
 the left cardinal caudal to it together form the hemiazygos vein. The por- 
 tion of the left cardinal cranial to the anastomosis loses its connection 
 with the duct of Cuvier (or coronary sinus) and becomes the accessory 
 hemiazygos vein (Fig. 234). The ascending lumbar veins, which join the 
 azygos and hemiazygos, probably do not represent persistent parts of the 
 caudal ends of the cardinals, but are formed by longitudinal anastomoses 
 between the original segmental lumbar veins. 
 
 The changes which occur in the region of the liver are of much im- 
 portance and result in conditions which bear no resemblance to the primary 
 ones. As has already been noted, the omphalomesenteric veins enter the 
 body at the umbilicus, pass cranially along the intestine and open into the 
 caudal end of the heart. The umbilical veins, which appear soon after, 
 enter the body at the umbilicus and pass cranially, one on each side, in the 
 ventro-lateral part of the body wall; at the level of the heart they turn 
 mesially through the septum transversum and join the corresponding 
 omphalomesenteric veins to form a common trunk on each side, into which 
 the duct of Cuvier then opens (Fig. 231). When the liver grows out as an 
 evagination from the intestine, it comes in contact with the proximal ends 
 of the omphalomesenteric veins and, as it enlarges, breaks them up into 
 numerous smaller channels (Fig. 237). 
 
 The blood then, instead of having a direct channel, is forced to flow 
 through these smaller channels which have been termed sinusoids. When 
 the liver has attained a considerable size a more direct and definite channel 
 is formed, which extends through the substance of the liver from the proximal 
 end of the right omphalomesenteric vein obliquely caudally to the left 
 omphalomesenteric vein. This newly formed channel is the ductus venosus 
 (Figs. 237 and 238). In the meantime, three transverse anastomoses develop 
 between the omphalomesenteric veins just caudal to the liver. The middle 
 one is dorsal to the intestine, the other two ventral, so that the intestine is 
 surrounded by two venous loops or rings (Figs. 237 and 238). At the same 
 time a cross-anastomosis develops between the left umbilical vein, which is 
 primarily the smaller, and the corresponding omphalomesenteric. This 
 anastomosis joins the omphalomesenteric at about the point where the latter 
 joins the ductus venosus, so that it seems to be a continuation of the ductus 
 venosus. A similar cross-anastomosis also develops between the right um- 
 bilical and right omphalomesenteric (Figs. 327 and 238). Thus the blood 
 
THE DEVELOPMENT OF THE VASCULAR SYSTEM 
 
 261 
 
 that is brought in from the placenta by the umbilical veins may pass through 
 the liver. Then the portion of each umbilical between the anastomosis and 
 the duct of Cuvier atrophies and disappears (Fig. 238). The remaining 
 portion of the left umbilical, which was originally the smaller, gradually 
 increases in size and finally carries all the blood from the placenta. The 
 right umbilical, on the other hand, loses its connection with the liver and 
 persists only as a small vein in the body wall, which opens into the left 
 umbilical vein near the umbilical cord (Fig. 239). Thus there is the peculiar 
 phenomenon of a vessel carrying blood in different directions at different 
 periods of its history. During the course of development of the septum 
 
 CEsophagus 
 
 Ant. cardinal 
 
 Post, cardinal 
 
 Liver 
 Right umbilical 
 
 Venous ring 
 Venous ring 
 
 Duct of Cuvier 
 Left umbilical 
 Ductus venosus 
 
 Left umbilical 
 
 Om phalomesenteric 
 Intestine 
 
 FIG. 238. Veins in the liver region of a human embryo of 4 mm. His, Kollmann's Atlas. 
 
 transversum and diaphragm the left umbilical is withdrawn from the body 
 wall and passes directly from the umbilicus to the ventral side of the liver. 
 During foetal life it conveys all the blood from the placenta to the liver. A 
 part of the blood is distributed in the liver, a part is carried directly to the 
 inferior vena cava by the ductus venosus (Fig. 240). After birth the 
 placental blood is cut off and the umbilical vein degenerates to form 
 the round ligament of the liver. 
 
 The venous rings around the intestine also undergo marked changes. 
 The right side of the most caudal and the left side of the most cranial dis- 
 appear; the remaining vessel finally loses its connection with the ductus 
 venosus and becomes the portal vein (Figs. 237, 238, 239 and 240). The 
 
262 
 
 TEXT-BOOK OF EMBRYOLOGY 
 
 portal vein is thus a derivative of the omphalomesenterics. After birth, 
 when the placental blood is cut off, blood is distributed in the liver by 
 branches of the portal vein, which represent the advehent hepatic veins; 
 it is collected again by branches which unite to form the revehent hepatic 
 veins, or hepatic veins proper, and the latter open into the inferior vena 
 cava. The advehent and revehent hepatic veins are formed by the 
 enlargement of some of the original sinusoids (Figs. 237 and 239). 
 
 Observations on the development of the veins in the extremities of human 
 
 Ant. cardinal 
 (int. jugular) 
 
 Post, cardinal 
 
 Sinus venosus and 
 orifice of ductus venosus 
 
 Revehent hepatic 
 
 Advehent hepatic 
 
 Right umbilical 
 
 Omphalomesenteric 
 (portal) 
 
 Umbilical vein 
 
 Ant. cardinal 
 (int. jugular) 
 
 Post, cardinal 
 Bronchus 
 
 Revehent hepatic 
 Advehent hepatic 
 
 Left umbilical 
 Umbilical cord 
 
 FIG. 239. Veins in the liver region of a human embryo of 10 mm. Kollmann's Alias. 
 
 embryos are so fragmentary that it seems advisable to make use of the work 
 that has been done on the rabbit. In the upper extremity the first vein to 
 develop is the primary ulnar vein which begins in the radial (cranial) side of 
 the extremity near its proximal end, extends distally along the radial border, 
 thence proximally along the ulnar (caudal) border, and opens into the 
 anterior cardinal vein (internal jugular) near the duct of Cuvier (Fig. 241). 
 This condition is present in rabbit embryos of thirteen days. A little later a 
 second vessel, the cephalic vein, appears as a branch of the external jugular, 
 
THE DEVELOPMENT OF THE VASCULAR SYSTEM 
 
 263 
 
 extends along the radial side of the extremity and becomes connected with 
 the digital veins (Fig. 242). When the digital veins are taken up by the 
 cephalic, the distal portion^ of the primitive ulnar undergoes regression. 
 These changes have taken place in rabbit embryos of fifteen days, and for a 
 short period the cephalic vein is the chief vessel of the extremity. The 
 primitive ulnar vein, however, develops more rapidly than the cephalic and, 
 
 Heart- 
 
 Inf. vena cava - 
 
 Ductus venosus 
 
 Left lobe of liver- 
 
 Umbilical vein 
 
 Umbilical ring 
 
 Hepatic veins 
 
 Right lobe of liver 
 
 Gall bladder 
 
 Portal vein 
 (omphalomesenteric; 
 
 Intestine 
 
 Inf. vena cava 
 
 FIG. 240. Veins of the liver (seen from below) of a human foetus at term Kollmann's Atlas. 
 
 with its branches, soon becomes the chief vessel; the portion in the forearm 
 gives rise to either the ulnar or basilic vein; the portion in the arm becomes 
 the brachial vein which then passes over into the axillary, and the latter 
 in turn passes over into the subclavian. The cephalic vein of the embryo 
 persists as the cephalic of the adult, and, during the period when it forms the 
 chief vessel of the extremity, a branch arises from it which becomes the radial 
 vein. Primarily the cephalic vein opens into the external jugular, but later 
 
264 
 
 TEXT-BOOK OF EMBRYOLOGY 
 
 Atjt. ca.r<L. 
 
 a new connection is formed with the axillary, while the original connection 
 
 persists as the j ugulocephalic (Fig. 243). 
 
 In a rabbit embryo of ten and one-half days a vein follows the border of 
 the lower extremity all the way round, connecting 
 on the cranial side with the umbilical and on the 
 caudal side with the posterior cardinal. This is the 
 primitive fibular vein, and from its course is homol- 
 ogous with the primitive ulnar vein of the upper 
 extremity (Fig. 241). From this time on, how- 
 ever, the course of development in the lower ex- 
 tremity differs from that in the upper. The con- 
 nection of the fibular vein with the umbilical is 
 soon lost. In older embryos (fifteen days) two 
 branches of the fibular vein have appeared; one 
 of these, the anterior tibial vein, _ begins on the 
 embryo of 14 days (u mm.), dorsum of the foot and extends diagonally proxi- 
 
 Modified from Lewis. . . ., , , 
 
 mally, to open into the fibular in the caudal 
 
 border; the other, the so-called connecting branch, begins as twigs in the ab- 
 dominal wall and tibial side of the extremity and opens into the fibular just 
 proximal to the opening of the anterior tibial (Fig. 242). Later the distal 
 
 FIG. 242. FIG. 243. 
 
 FIG. 242. Diagram of the veins in the extremities of a rabbit embryo of 14 days 
 
 and 18 hours (14.5 mm.). Modified from Lewis. 
 
 FIG. 243. Diagram of the veins in the extremities of a rabbit embryo of 17 days 
 (21 mm.). Modified from Lewis. 
 
 part of the primitive fibular is broken up by the differentiation of the digits 
 (toes) and disappears almost up to the point of junction with the anterior 
 tibial. The latter enlarges and receives the digital branches, and appears 
 
THE DEVELOPMENT OF THE VASCULAR SYSTEM 
 
 265 
 
 as a continuation of the proximal part of the primitive fibular. The anterior 
 tibial and primitive fibular together thus constitute the sciatic vein (Fig. 
 243). Another vessel appears in embryos of fifteen days, which represents 
 the beginning of the femoral vein and opens into the cardinal, cranial to the 
 opening of the sciatic (Fig. 243). From this time on the femoral, with its 
 branches, enlarges at the expense of the other veins and becomes the principal 
 vein of the lower extremity. In the human embryo the femoral anastomoses 
 with the sciatic near the knee and the proximal portion of the sciatic then 
 atrophies, the distal portion persisting as the small scphenous vein. The 
 
 Sup. vena cava 
 Lungs 
 
 Right atrium 
 
 Right ventricle 
 
 Inf. vena cava 
 
 Liver 
 
 Ductus venosus 
 
 Placenta 
 
 Inf. vena cava 
 
 Umbilical vein 
 Umbilical artery 
 
 Ant. part cf body 
 
 Carotid and 
 subclavian arteries 
 
 Ductus arteriosus 
 
 Pulmonary artery 
 Left ventricle 
 
 Post, part of body 
 
 FIG. 244. Diagram illustrating the foetal circulation. Compare with Fig. 245. 
 
 Modified from Kollmann. 
 
 The shading represents the relative impurity of the blood in different regions, the 
 darkest shading representing the most impure blood 
 
 large saphenous vein and the posterior tibial vein possibly are derivatives of 
 the femoral, but this question has not been settled. 
 
 CHANGES IN THE CIRCULATION AT BIRTH. During fcetal life the course of 
 the blood is adapted to the placental circulation, since the placenta is the 
 only means by which the blood is purified and from which the foetus derives 
 its nutriment. The pure blood from the placenta passes through the umbil- 
 ical vein to the liver; there a part of it is distributed to the liver by some of 
 the advehent veins, is collected again by the revehent veins and poured into 
 the inferior vena cava; a part passes directly to the vena cava through the 
 
266 
 
 TEXT-BOOK OF EMBRYOLOGY 
 
 ductus venosus. At this point the blood acquires some impurity from the 
 stream brought in by the vena cava itself and the portal vein. The slightly 
 impure blood then flows into the right atrium, is directed by the Eustachian 
 valve through the foramen ovale into the left atrium, thence flows into the 
 left ventricle and is forced out into the aorta. A part of the blood flows on 
 through the aorta, a part is carried to the upper extremities and head and 
 neck regions by the subclavian and carotid arteries. The latter part, then 
 becoming impure, is carried back to the right atrium by the subclavian 
 
 Sup. vena cava 
 Lungs 
 
 Pulmonary veins 
 Right atrium 
 
 Right ventricle 
 Inf. vena cava 
 
 Hepatic vein 
 Liver 
 
 Inf. vena cav 
 
 Ant. part cf body 
 
 Carotid and 
 subclavian arteries 
 
 Pulmonary artery 
 
 Left ventricle 
 
 Aorta 
 
 Hepatic artery 
 
 Portal vein 
 
 Intestinal 
 circulation 
 
 Post, part of body 
 
 FIG. 245. Diagram illustrating the circulation in the adult. Compare with Fig. 244. The 
 shading represents the relative impurity of the blood, the white being the purest blood. 
 
 and jugular veins and superior vena cava; from the right atrium the greater 
 portion flows into the right ventricle and thence is forced out into the large 
 pulmonary artery. But since the lungs are non-functional, this blood passes 
 through the ductus arteriosus to join the stream in the aorta. The blood 
 received by the more cranial portion of the foetus is but slightly impure, 
 for the impure blood from the ductus arteriosus joins the aortic stream distal 
 to the origin of the subclavian and carotid arteries. This accounts for 
 the fact that the more cranial portion of the body generally is better devel- 
 oped than the more caudal portion. It is well to note here that the liver 
 
THE DEVELOPMENT OF THE VASCULAR SYSTEM 267 
 
 receives purer blood than any other part of the body, and this is undoubtedly 
 correlated with the relatively enormous size of that organ in the foetus. 
 The rather impure blood which starts through the dorsal aorta is in part 
 distributed to the viscera, body walls, and lower extremities by the visceral 
 and segmental arteries, and thence is collected by the branches of the portal 
 vein and inferior vena cava to be returned as impure blood to the umbilical 
 current at the liver; in part it is carried by the umbilical arteries to the pla- 
 centa, there to be purified and collected by the branches of the umbilical 
 vein (see Fig. 244). 
 
 At birth, when the placental circulation is cut ofT, the proximal end of the 
 umbilical vein atrophies to form the round ligament of the liver; the ductus 
 venosus also atrophies and becomes merely a connective-tissue cord in the 
 liver. The hepatic portal circulation is still maintained by the portal vein. 
 The foramen ovale is closed and the impure blood from the inferior vena cava 
 as well as that from the superior, passes from the right atrium into the right 
 ventricle and thence is forced out through the pulmonary artery to the lungs, 
 which at this time become functional, and is returned to the left atrium by the 
 pulmonary veins. The ductus arteriosus atrophies to form the ligamentum 
 arteriosum. From the left atrium the pure blood flows into the left ventricle, 
 thence is forced out through the aorta and its branches to all parts of the 
 body. At the same time the more distal portions of the umbilical arteries in 
 the embryo atrophy to form the lateral umbilical ligaments, their proximal 
 portions persisting as the superior vesical arteries (see Fig. 245). 
 
 Haemopoiesis Histogenesis of the Blood Cells. 
 
 Two sharply contrasting views are held regarding the origin and genetic 
 relationships of the different kinds of blood cells. The one view, expressed 
 in the monophyletic theory, holds that there is differentiated out of the mesen- 
 chyme a certain type of cells the primitive blood cells, or haemoblasts 
 and that from this single type all the cells of the blood arise through proc- 
 esses of development along divergent lines. The other view, expressed in 
 the polyphyletic theory, holds that while the blood cells are of mesenchymal 
 origin the red cells and white cells have a dual origin, each type arising from 
 its own mother-cells ; and further that perhaps each kind of white cells arises 
 from a distinct parent-cell. The recent extensive studies of the problem 
 have yielded evidence that turns the balance at present in favor of the mono- 
 phyletic theory, and the following account is based in the main upon these 
 studies, particularly those of Maximow on the rabbit and Dantschakoff on 
 the chick. 
 
 The sites of blood formation, or haemopoiesis, are (i) the area opaca 
 
268 
 
 TEXT-BOOK OF EMBRYOLOGY 
 
 (yolk sac), (2) the body mesenchyme, including the endotheiium of the early 
 blood vessels, (3) the liver and spleen, (4) bone marrow, and (5) the lymph 
 glands. These various structures are functional at successive periods of 
 development of the embryo, but overlap to a certain extent, the marrow and 
 lymph glands being probably the only foci of origin of blood cells in the adult. 
 In the area opaca blood-cell development is initiated in the formation of 
 the blood islands. Some of the mesenchymal cells become less irregular in 
 shape by retraction of their protoplasmic processes and isolation from the 
 general syncytium. They assume amoeboid properties and the cytoplasm 
 
 ** 
 
 FIG. 246. Mesenchyme from a rabbit embryo at the time of beginning blood formation. 
 
 Maximow. 
 
 m, Ordinary mesenchyme cells; m f , mesenchyme cell in mitosis; /, primitive blood cell 
 
 (primitive lymphocyte). 
 
 acquires a distinctly basophilic character (Fig. 246). These then represent 
 primitive blood cells, or hcemoblasts. Maximow has given them the name 
 primitive lymphocytes, or lymphoblasts, regarding them as the common an- 
 cestors of all the blood cells. Clusters of these cells constitute the blood 
 islands which are involved in the development of the primitive blood spaces, 
 the superficial cells being transformed into endotheiium (see p. 217) and the 
 central cells remaining as primitive lymphocytes. Other primitive lympho- 
 cytes also differentiate in the mesenchyme outside of the blood spaces, 
 afterward probably entering the vessels by virtue of their amoeboid properties. 
 
THE DEVELOPMENT OF THE VASCULAR SYSTEM 
 
 269 
 
 There is a view that both the blood cells and the endothelium of blood 
 vessels arise from certain mesamceboid cells of entodermal origin, which are 
 insinuated between the entoderm and mesoderm but are not in the strict 
 sense constituents of the latter, and which collectively have been called the 
 angioblast. While the mesamceboid cells are probably identical with the 
 primitive lymphocytes, the idea that they constitute a set of specific rudi- 
 ments of entodermal origin, from which both blood cells and endothelium 
 arise, has not been generally accepted. The view, however, is not discord- 
 ant with the monophyletic concept of the origin of blood cells. 
 
 FIG. 247. Portion of a blood vessel from the yolk sac of a rabbit embryo, showing various 
 
 stages in the formation of erythrocytes. Maximow. 
 0, megaloblasts; a', megaloblast in mitosis; b, normoblasts; b', normoblast in mitosis; c, erythro- 
 
 blasts; d, erythrocyte, not yet discoid; en, endothelium; /, primitive lymphocytes; 
 
 k, normoblast recently divided; n, shrunken erythroblasts (?); n', extruded nucleus. 
 
 The primitive lymphocytes (of Maximow), constituting the parent stem 
 from which all the blood cells arise according to the monophyletic theory, 
 specialize at first in two general directions. In one direction the specializa- 
 tion leads toward the erythrocytes, or red blood corpuscles, and in the other 
 toward the leucocyte, or white blood cell, series including the myelocytes. 
 In the former case the lymphocytes become modified in that the cytoplasm 
 becomes less basophilic and acquires a trace of haemoglobin; the nuclei become 
 
270 
 
 TEXT-BCOK OF EMBRYOLOGY 
 
 somewhat eccentric, the chromatin network a little denser and the nucleoli 
 less conspicuous. While these changes are in progress the cells multiply by 
 mitosis. The resulting cells are termed megaloblasts (Fig. 247, a). These 
 continue to multiply by mitosis, the cytoplasm acquiring more haemoglobin 
 and the nuclei becoming more dense, the resulting cells being somewhat 
 smaller and known as normoblasts (Fig. 247, b). The normoblasts, still divid- 
 ing by mitosis, acquire still more haemoglobin and become erythroblasts (Fig. 
 247, c). These lose their nuclei and thus become erythrocytes, the definitive 
 red blood corpuscles. The manner in which the nuclei are lost is a matter 
 of dispute. Some claim it is absorbed (karyolysis) ; others claim it is extruded 
 
 (karyorrhexis) (Fig. 248) ; recently the 
 observation has been made that the 
 nucleus with a small amount of sur- 
 rounding cytoplasm escapes from the cell 
 in a manner resembling constriction. 
 
 In the specialization leading to the 
 white blood cell series, the parent stem 
 cell (primitive lymphocyte) proliferates 
 by mitosis and undergoes certain di- 
 vergent changes in its nucleus and cyto- 
 plasm which yield the characters of the 
 various kinds of leucocytes. Some of 
 the cells become polymorphonuclear and 
 acquire neutrophile granules to become 
 neutrophile leucocytes; others acquire 
 acidophile granules as acidophiles; still 
 others, basophile granules as basophiles. 
 The large mononuclear leucocytes, with the transitional forms having the 
 horseshoe-shaped nuclei, possibly represent but slightly modified primitive 
 lymphocytes. The definitive lymphocytes are probably derived from the 
 primitive by division and but slight changes in character. Thus the vari- 
 ous forms of white blood cells would not represent different stages in a series 
 but divergent lines of specialization from a parent stem. 
 
 As mentioned before, the various blood forming organs function as such 
 at successive stages of development of the embryo. The mesenchyme 
 generally, both in the yolk sac and in the body, gives rise to blood cells during 
 the earlier stages and may continue to do so until relatively late in embryonic 
 life as has been demonstrated in the chick. It is interesting to note in this 
 connection that in certain regions endothelial cells may also be transformed 
 into primitive blood cells. In the earlier stages of liver development active 
 haemopoiesis is observed in the sinusoids, probably partly from cells carried in 
 
 FIG. 248. Showing the escape of the nuclei 
 from nucleated red blood cells. Howell. 
 
 I, 2, 3, 4, represent stages of extrusion 
 observed in living cells; a, from circulat- 
 ing blood of adult cat after bleeding four 
 times; b, from young kitten after bleed- 
 ing; c, from 90 mm. cat embryo; others 
 from marrow of adult cat. 
 
THE DEVELOPMENT OF THE VASCULAR SYSTEM 
 
 271 
 
 by the blood stream and partly from primitive blood cells derived from the 
 neighboring mesenchyme (Fig. 249). This function ceases in the liver in later 
 embryonic life. The formation of blood cells takes place in the developing 
 spleen but erythrocyte formation ceases after birth, although following severe 
 haemorrhage the function may be resumed even in adult life. The formation 
 of lymphocytes, however, goes on throughout life in the splenic corpuscles. 
 
 FIG. 249. From the liver of a rabbit embryo, showing formation of red blood cells. Maximow. 
 a, Megaloblasts; a', megaloblast in mitosis; b, normoblasts; c- erythroblasts; en, en', en", endothe- 
 lial cells; h, liver cells; I, primitive lymphocytes; /', primitive lymphocyte in mitosis; 
 , nucleus being extruded from small erythroblast. 
 
 The lymph glands are constant sources of lymphocytes, the parent cells being 
 the large mononuclear cells found in the germinal centers. These cells are 
 regarded as closely allied to the primitive lymphocytes, perhaps even 
 identical, although here in this particular environment giving rise only to the 
 lymphocyte line. 
 
 The bone marrow is an important source of blood cells in the embryo, 
 and in the adult under normal conditions is regarded as the only source of 
 
272 TEXT-BOOK OF EMBRYOLOGY 
 
 red corpuscles. The parent stem cells, here called myeloblasts, are recog- 
 nizable in the form of large mononuclear, non-granular cells, with the general 
 characters of primitive lymphocytes, which give rise to the red blood cells 
 through clearly distinguishable megaloblast and normoblast stages, and to 
 the various forms of leucocytes and lymphocytes. In addition the parent 
 
 m. ' .W - 
 
 m ^*'$j$f+ 
 
 / T^vi^W^^I^' w^ 
 
 \/S^. V^+P' l 
 
 *: *V 
 
 f * , J w i ,,_ ^P ^^ 
 
 " 
 
 m" 
 
 m * ^ } ' ^Ji M^jf^i ^ 
 
 .^S% . * ^ ' *T;" T " m/ 
 
 ^. 
 
 /w 
 
 FIG. 250. From a section of red marrow from the femur of a young rabbit. Schdfer. 
 e, Erythrocytes; e'. normoblasts; e", normoblast in mitosis; /, outlines of fat cells; /, polymor- 
 phonuclear leucocytes; m, neutrophile myelocytes; m', myelocytes in mitosis; m", 
 eosinophile myelocytes; m'", basophile myelocytes. 
 
 cells also give rise to certain other cells which are normally confined to the 
 marrow, viz., the myelocytes. These are large mononuclear cells, with 
 vesicular nuclei, the cytoplasm containing neutrophile, acidophile, or baso- 
 phile granules similar to those of the leucocyte series (Fig. 250). The 
 genetic relationships of the " giant" cells, or myeloplaxes, in the marrow are 
 not clear. The myeloplaxes are large masses (30 to 100 micra in diameter) 
 
THE DEVELOPMENT OF THE VASCULAR SYSTEM 
 
 273 
 
 of homogeneous or finely granular, slightly basophilic cytoplasm containing 
 either a single tabulated, annular nucleus (megakaryocytes , Fig. 250, meg) 
 or many nuclei (polykaryocytes). The polykaryocytes have been considered 
 identical with the osteoclasts, which may represent fused osteoblasts, but 
 this relationship has not been definitely established. Both kinds of cells 
 have been considered as derivatives of the myeloblasts, the polykaryocytes 
 being later stages of megakaryocytes. 
 
 The blood platelets are now regarded by some authors as derivatives of 
 the megakaryocytes; pseudopodia of the latter breaking off and gaining 
 access to the blood stream. By others they are not believed to be formed 
 constituents of the circulating blood, but appear only after shed blood 
 comes in contact with a foreign substance. 
 
 The accompanying table, which is a tentative graphic scheme of the 
 monophyletic theory, will assist the student in tracing the lineage of the 
 blood cells. 
 
 Primitive lymphocyte (Maximow) 
 Primitive blood cell Haemoblast 
 
 Primitive 
 blood cell 
 
 / 
 
 Lymphocytes 
 
 Polymorph 
 
 Granular Non-granular 
 \ l\ 
 
 Momonuclear \ Mononnclear 
 
 Transitional I Transitional 
 
 Neutrophile Basophile Basophile 
 Acidophile Neutrophile Acidophile 
 Acidophile Neutrophile 
 
 \ 
 Megaloblast 
 
 Normoblast 
 Erythroblast 
 
 Erythrocyie 
 \ 
 Megaloblast 
 
 etc. 
 
 Primitive 
 blood cell 
 
 Lymphocytes 
 
 Myelol 
 
 Neutrophile 
 myelocyte 
 Acido 
 myelo 
 
 alast Leucocyte series 
 \ (as above) 
 Basophile 
 myelocyte 
 
 plille 
 cyte 
 
 Primitive 
 blood cell 
 etc. 
 
 THE LYMPH VASCULAR SYSTEM. 
 
 A controversy has arisen over the origin of the lymph channels and their 
 endothelium, similar to the one that arose over the genesis of the blood vessels. 
 There are therefore two main views, viz.: (i) that the endothelium of the 
 lymph vessels arises as sprouts from the endothelium of veins and continues 
 to grow by proliferation and migration of its own cells, the lymphatics thus 
 
274 
 
 TEXT-BOOK OF EMBRYOLOGY 
 
 being direct derivatives of the venous channels; (2) that the lymph vessels 
 arise in situ through enlargement and coalescence of intercellular tissue 
 spaces, the mesenchymal cells bounding these spaces becoming flattened and 
 rearranged to form the endothelial walls of the vessels, and, as a corollary, 
 that the junction of the lymph vessels with the veins, which occurs at certain 
 definite points, is a secondary matter. 
 
 Here again the scope of the work does not permit presentation in detail 
 
 Ant. cardinal vein f~ 
 Subclavian vein 
 
 Post, cardinal vein --/-/-- 
 
 I 
 
 Diaphragm- 
 
 Suprarenal gland - 
 Mesonephros- 
 
 . Kidney- 
 
 Ant, lymph heart 
 
 Deep lymphatics 
 
 of arm 
 
 Branches to heart 
 
 Branches to lung 
 
 Aorta 
 
 Branch to oesophagus 
 
 Branches to stomach 
 
 Branch to duodenum 
 
 Branches to mesenteric plexus 
 Cisterna chyli 
 
 Post, lymph heart 
 
 Deep lymphatics 
 
 to leg 
 
 * / \l ^ * , 
 
 FIG. 251. Diagram showing the arrangement of the lymphatic vessels in a 
 pig embryo of 40 mm. Sabin. 
 
 of the evidence adduced in favor of either of these views. The advocates 
 of the first view have placed much dependence upon the method of in- 
 jection, which, as in the case of the origin of blood vessels, has been met 
 with the criticism that injection shows only those lymph channels with con- 
 tinuous lumina and leaves undetermined the field beyond the injected area 
 (see page 225). To supplement their studies by the injection method, the 
 investigators who maintain that lymphatic endothelium grows by sprouting 
 of preexisting endothelium have added studies on living tissues in which 
 the sprouting phenomena are claimed to be clearly observable. Those who 
 
THE DEVELOPMENT OF THE VASCULAR SYSTEM 
 
 275 
 
 maintain that the lymphatics and their endothelium arise in situ from 
 intercellular tissue spaces and the bordering cells, argue that the same 
 principles underlie the formation of lymphatics that determine blood-vessel 
 development and that it has been shown experimentally that blood vessels 
 develop in regions which have been entirely cut off from any source of endo- 
 thelium except the mesenchymal cells 
 in situ (see page 225). 
 
 According to the first view lym- 
 phatic development can be divided into 
 two stages: (i) the formation of isolated 
 lymph sacs, derived from veins, which 
 become united into a system, and (2) 
 the peripheral growth of lymph vessels 
 which sprout from the endothelium of 
 these sacs and spread through the body, 
 (i) The first sacs appear, one on each 
 side, along the jugular (anterior cardi- 
 nal) veins. The branches of these veins 
 at first form a plexus; a portion of the 
 plexus becomes cut off from the parent 
 stems and lies as a series of isolated 
 spaces in the mesenchyme ; these spaces 
 then enlarge and coalesce to form an en- 
 do thelial-lined sac the jugular lymph 
 sac or heart which afterward joins the 
 jugular vein by a new opening (Fig. 
 251). A second pair of sacs the pos- 
 terior lymph sacs or hearts develops 
 in the same manner from the more 
 caudal branches of the posterior cardi- 
 nal veins (Fig. 251). Two other sac- 
 like structures develop the cisterna 
 
 chyli and retroperitoneal sac the former in the region of the renal veins 
 and the latter in the vicinity of the suprarenal bodies. Through the longi- 
 tudinal fusion of the chain of sac-like structures, the axial lymphatic drain- 
 age line of the body is established (Fig. 251). The thoracic duct probably 
 represents the fused cisterna chyli and jugular lymph hearts. The lymph 
 hearts in the avian and mammalian embryo become relatively smaller as 
 development proceeds until in the adult they are barely discernible as slight 
 dilatations in the lymph vessels. The cisterna chyli, however, may persist 
 as a clearly distinguishable dilatation at the caudal end of the thoracic duct. 
 
 FIG. 252. Diagram showing network of 
 lymphatic vessels in skin of pig embryos. 
 Sabin. 
 
 Area marked A shows extent of network in 
 an embryo of 18 mm.; B, in embryo cf 
 20 mm.; C, in embryo of 30 mm.; D, in 
 embryo of 40 mm. 
 
276 
 
 TEXT-BOOK OF EMBRYOLOGY 
 
 (2) The peripheral lymph channels, which drain into the thoracic duct, 
 represent outgrowths from the lymph sacs. From the jugular sacs sprouts 
 
 FIG. 253. From cross-sections of cat embryos in successive stages (a, b, c, d) of development, 
 in the region of the jugular lymph sac ; diagrammatic but amply supported by studies of serial 
 sections and reconstructions. Huntington. 
 
 i, Anterior cardinal vein; 2, somatic tributary of same; 4, developing blood cells in the mesen- 
 chyme; 5, mesenchymal intercellular spaces rudiments of the jugular lymph sac; 6, rudi- 
 ments of brachio-cephalic venous anastomosis; 7, brachio-cephalic venous anastomosis; 8, 
 haemophoric lymphatic plexus forerunner of jugular lymph sac; n, thoracic duct- 
 'approach' of jugular lymph sac; 12, rudiments of thoracic duct; 13, jugular lymph sac pre- 
 paring to rejoin vein and to establish secondary connection with rudiments of thoracic 
 duct (12) and of other systemic lymphatics (14); 15, jugular lymph sac, which has re- 
 joined vein through permanent lymphatico-venous tap (16); 17, thoracic duct; 18, jugular 
 and cephalic systemic lymphatics. 
 
 invade the neck, head, shoulders, and finally the entire upper extremities 
 and upper part of the body wall (Fig. 252). Similarly, from the posterior 
 lymph hearts sprouts invade the lower extremities and lower portion of the 
 
THE DEVELOPMENT OF THE VASCULAR SYSTEM 
 
 277 
 
 body wall (Fig. 252) . Outgrowths from the original axial drainage line invade 
 the various visceral organs (Fig. 251). Thus the lymphatic drainage of the 
 body is effected through outgrowths from a few primary centers which 
 represent derivatives of the venous channels. The lymph glands are second- 
 ary foci of development along the lymph vessels (see page 280), 
 
 The view that lymphatics arise as enlarged isolated intercellular spaces 
 in the mesenchyinal tissue does not include any dispute as to the general 
 
 FIG. 254. From a photograph (X 600) of a cross-section through the caudal end of a chick 
 
 embryo of 15 mm., showing enlarged mesenchymal intercellular spaces as rudiments 
 
 of the posterior lymph sac. West. 
 3, Coccygeal vein; 6, caudal muscle plate; 8, isolated enlarged intercellular spaces, the bounding 
 
 cells becoming flattened; 9, lateral branch of coccygeal vein; 10, lymphatics containing 
 
 collections of developing blood cells. 
 
 disposition of the lymph channels in the body, but comprises a funda- 
 mentally different concept of the origin of these vessels. Upon a long and 
 exhaustive series of observations on closely graded series of embryos of 
 Fishes, Amphibia, Reptiles, Birds, and Mammals is based the conclusion 
 that not only the lymph sacs but the peripheral lymphatics as well originate 
 independently of the veins; and that the opening of the main lymphatic 
 drainage lines into the jugular or subclavian veins near their junction, 
 
278 
 
 TEXT-BOOK OF EMBRYOLOGY 
 
 and into the inferior vena cava and renal veins (in some monkeys) , is second^ 
 arily established. The same hydrodynamic mechanical factors regarded 
 as operative in the formation of blood vessels, viz.: pressure and friction 
 incident to blood flow (see page 226), are considered as effective likewise 
 in the development of lymphatics. Fundamentally, therefore, the lymph 
 vascular system from the viewpoint of development differs in no wise from 
 the blood vascular system/ 
 
 \ 
 
 FIG. 255. Diagrams showing three stages (a, b, c) in the development of the thoracic duct in 
 the cat embryo, in which the jugular lymph sac has established two permanent venous 
 connections (8 and 9). Huntington. 
 
 i, Anterior cardinal vein; 2, duct of Cuvier; 3, posterior cardinal vein; 4, external jugular- 
 cephalic vein; 5, subclavian vein; 6, jugular lymph sac; 7, thoracic duct 'approach' of 
 lymph sac; 8, common jugular opening of lymph sac; 9, jugulo-subclavian opening of lymph 
 sac; 10, rudiments of thoracic duct; n, thoracic duct. 
 
 The lymph sacs, both jugular and posterior, arise through enlargement 
 and confluence of mesenchymal intercellular spaces, the cells bounding the 
 spaces becoming flattened and rearranged to form endothelium. In the 
 case of the mammalian (cat) jugular sac, intercellular spaces in the region 
 dorso-lateral to the anterior cardinal vein unite into an intricate plexus of 
 channels which then opens into the vein (Fig. 253, a and b). Following 
 this the components of the plexus enlarge and coalesce to form the sac, 
 which then temporarily severs connection with the vein (Fig. 253, c). Finally 
 the sac effects a permanent connection with the vein through one or more 
 
THE DEVELOPMENT OF THE VASCULAR SYSTEM 279 
 
 openings which represent the lymphatico-venous communications of the 
 adult (Fig. 253, d). In the case of the posterior sac, intercellular spaces 
 dorsal to the posterior cardinal vein (.Fig. 254, 8) first form a plexus the 
 components of which then unite into a large endothelial-lined space which 
 opens into the dorsal tributaries of the vein. 
 
 The thoracic duct also arises as a chain of isolated endothelial-lined 
 spaces along the line of the aorta. These unite longitudinally into a con- 
 tinuous channel which joins the jugular lymph sac, thus forming the axial 
 lymphatic drainage line of the body (Fig. 255, a, b, c). In reptilian embryos 
 the spaces first fuse into a distinct periaortic plexus out of which the thoracic 
 duct is established. In the avian embryo the chain of spaces follows the 
 general line of the aorta but does not become so intimately associated with 
 the great arterial trunk as in reptiles. In the mammalian forms rudiments 
 of the thoracic duct follow the same general plan of development, but are 
 associated topographically with the ventro-medial tributaries of the azygos 
 veins. These tributaries finally become detached from the larger venous 
 trunks, atrophy and disappear, being replaced by the thoracic duct. 
 
 On the same principles laid down for the development of the lymph sacs 
 and thoracic duct, the peripheral lymphatics also are developed. In all 
 the regions of the body not immediately drained by the lymph sacs or 
 thoracic duct, mesenchymal intercellular spaces enlarge and coalesce, the 
 cells bounding the coalesced spaces being transformed directly into endo- 
 thelium; the spaces unite to form a plexus of endothelial-lined channels, 
 and in this plexus certain channels increase in size to form the larger lym- 
 phatics which converge and eventually join the main axial drainage line. 
 Thus the lymphatic drainage of the entire body is established. 
 
 One of the most interesting and significant phases of lymphatic develop- 
 ment, which has been brought out through recent studies of the problem, is 
 the role played by certain early lymph channels in conveying blood cells to 
 the general circulation. It has been found that, in the region subsequently 
 occupied by the lymph sacs, extensive blood cell formation (haemopoiesis) 
 occurs prior to the formation of lymphatic rudiments. As the lymph spaces 
 appear and unite into a plexus the developing blood cells are included within 
 them (Fig. 253, a and Fig. 254, 10). When the lymphatic plexus joins 
 the veins the blood cells are carried into the general circulation (Fig. 253, b). 
 This haemophoric function of the early lymph channels is especially prominent 
 in the case of the thoracic duct in the chick. Here extensive collections of 
 blood cells develop in the mesenchymal tissue along the line of the aorta 
 and become included within the rudiments of the thoracic duct and eventu- 
 ally, when the latter unites with the jugular lymph sac, are carried into the 
 veins and thus enter the general circulation. After these early lymphatics, 
 
280 
 
 TEXT-BOOK OF EMBRYOLOGY 
 
 which transport blood cells and which have been denned as haemophoric 
 lymphatics, or veno-lymphatics, fulfil their haemophoric function they are 
 retained as permanent lymph channels in the general lymphatic organiza- 
 tion. In a broader interpretation, the haemophoric function of certain 
 lymph vessels during ontogeny is particularly significant in that it indicates 
 essential and fundamental similarity of lymphatic vascular development to 
 haemal vascular development. 
 
 The Lymph Glands. 
 
 The lymph glands do not begin to develop for some time after the lym- 
 phatic vessels, since there are no indications of them in the human fcetus 
 until the latter part of the third month and none in pig embryos until thev 
 
 Efferent lymph, ves. 
 
 Blood vessel 
 
 -ji^Marginal sinus 
 $5'*' Capsule 
 
 *--l!7$ 
 
 Afferent 
 lymph, ves. 
 
 FIG. 256. From a section through the axilla of a human embryo of 125 mm. (4-5 months), 
 showing an early stage of a lymph gland. Kling. 
 
 have reached a length of 30 mm. While it is definitely settled that lymph 
 glands originate in very close relation with the lymphatic vessels, certain 
 points in their later development need further study. In the axilla and 
 groin, for example, the lymphatic vessels form a dense network in the meshes 
 of which are masses of connective tissue. These masses become more 
 cellular and with the surrounding vessels constitute the anlagen of lymph 
 glands (Fig. 256). The new cells which appear in the masses are lympho- 
 cytes which may pass through the walls of the neighboring blood vessels and 
 lodge here or may be derived directly from connective tissue (mesenchymal) 
 cells in situ. Whatever the origin of the lymphocytes may be, they have the 
 opportunity here to divide freely. The mass becomes still more cellular and 
 enlarges at the expense of the lymphatic vessels which then come to form a 
 
THE DEVELOPMENT OF THE VASCULAR SYSTEM 
 
 281 
 
 network around the mass. This network is the marginal plexus, and it 
 communicates freely with the neighboring lymphatic channels. Within 
 the mass of cells blood vessels are present from the beginning, and these 
 are destined to be the blood vessels of the lymph gland, and the point of their 
 entrance and exit marks the hilus. Outside of the marginal plexus the con- 
 nective tissue condenses to form the capsule. The gland at this stage thus 
 consists of a central compact cellular mass, made up of connective tissue 
 and lymphocytes, in which blood vessels ramify; a plexus of lymphatic 
 channels around the mass which communicate with the neighboring channels ; 
 and around the whole structure a capsule of connective tissue (Fig. 256). 
 Further development consists of the breaking up of the cell mass by 
 
 Afferent lymphatic vessels 
 
 Marginal sinus 
 
 Dense lymph, 
 tissue 
 
 Intermediary 
 plexus 
 
 Efferent lymph, vessel 
 
 Blood vessels 
 
 FIG. 257. Diagram illustrating a stage (later than Fig. 256) in the development 
 of a lymph gland. Stohr. 
 
 lymphatic channels and the formation of the follicles. It seems probable 
 that branches from the marginal plexus invade the cell mass principally 
 from an area around the hilus, thus breaking it up into smaller irregular 
 masses or cords. At the side opposite the hilus the invading channels are less 
 numerous, leaving larger parts of the mass which become the follicles (nodules) 
 of the cortex. On all sides the invading channels communicate with the 
 marginal plexus and form the so-called intermediary plexus. The gland as 
 a whole enlarges and its peripheral part pushes outward into the surrounding 
 tissue. Over the follicles the capsule is pushed outward, while between them 
 it remains in place and comes to dip into the gland as the trabecula. The 
 blood vessels tend to lie in the trabeculae, but a small branch probably 
 passes to each follicle. In the follicles themselves the lymphocytes pro- 
 
282 TEXT-BOOK OF EMBRYOLOGY 
 
 liferate and the central part of each follicle becomes a germinal center. The 
 connective tissue among the lymphatic vessels composing the marginal plexus 
 becomes proportionately less as the vessels enlarge and finally exists only as 
 strands of reticular tissue which, naturally, are covered by the endothelium ; 
 thus the marginal plexus becomes the marginal sinus. The intermediary 
 sinus is formed by the channels which originally invaded the cell mass. The 
 reticular tissue is probably composed of remnants of the original connective 
 tissue. All the channels converge at the hilus to form the efferent lymphatic 
 vessels (Figs. 257 and 258). 
 
 The haemolymph glands are probably developed in much the same 
 
 Afferent lymph, vessels 
 
 Marginal 
 plexus 
 
 Lymph follicle 
 
 Medullary cord 
 
 Intermediary, 
 nlexus 
 
 nvm ^Ka ^ ^ . - * - * -* ** > Trabecula 
 
 Capsule^ 'f\**^ 
 
 Efferent lymph, vessels 
 
 FIG. 258. Diagram illustrating a late stage in the development of a lymph gland. 
 Compare with Fig. 257. Stohr. 
 
 manner as the lymph glands except that in the former the sinuses are filled 
 with red blood cells. 
 
 The first lymph glands to develop are those in the axilla, in the inguinal 
 region, in the neck, and in the base of the mesentery. These are the so-called 
 primary glands and develop during fcetal life. They are of constant occur- 
 rence in these regions, but vary in number in different individuals. The 
 secondary lymph glands are those in the bend of the elbow, in the popliteal 
 space, in the mesentery, and around the aorta. Some of these develop during 
 fcetal life and some later. While lymph glands are of constant occurrence in 
 some regions throughout life, the number may vary at different times in any 
 region; and there may also be variations in different individuals. Glands 
 may be called into existence at any time during life, in almost any region, 
 as the result of exceptional activity of some organ, or in pathological con- 
 ditions. Such structures are known as tertiary lymph glands. 
 
THE DEVELOPMENT OF THE VASCULAR SYSTEM 283 
 
 The origin of the lymph (plasma) itself is probably extremely complex. 
 A.t one time it was considered as the result of nitration from the blood plasma 
 through the capillary walls. If lymph originates in this way the nitration 
 is selective, for the chemical composition of the lymph differs from that of 
 the blood plasma. In all probability the lymph plasma consists of blood 
 plasma which has escaped through the vessel walls plus the products of cell 
 activity in the tissues. 
 
 The Spleen. 
 
 Since the spleen is generally considered as a lymphatic organ and since 
 recent researches have shown that its structure is quite comparable to that 
 of the lymph glands, it seems advisable to consider it under the head of lym- 
 phatic organs. Its ultimate origin is not yet settled and the details of its 
 later development are still obscure. The same difficulties are met with as in 
 the case of the origin and development of blood cells, for it is known that the 
 spleen plays a part in the formation of the blood cells. Its structure differs 
 from that of the lymph glands chiefly in that it possesses no distinct lym- 
 phatic sinuses; but it does possess lymph follicles (splenic corpuscles) and 
 densely cellular cords (pulp cords) which are separated by cavernous blood 
 vessels (cavernous veins). 
 
 For some time the spleen was considered as a derivative primarily of the 
 mesenchyme in the region of the dorsal mesogastrium. More recently, 
 however, investigators have taken the view that it arises partly, or possibly 
 entirely, from the mesothelium (ccelomic epithelium) of the dorsal mesogas- 
 trium. In human embryos during the fifth week the anlage of the spleen 
 appears as an elevation on the left (dorsal) side of the mesogastrium (Fig. 
 259). This elevation is produced by a local thickening and vascularization 
 of the mesenchyme, accompanied by a thickening of the mesothelium 
 which covers it; and, furthermore, the mesothelium is not so distinctly 
 marked off from the mesenchyme as in other regions. Cells from the 
 mesothelium then migrate into the subjacent mesenchyme and the latter 
 becomes much more cellular (Fig. 260). The migration is brief, and in 
 embryos of about forty-two days has ceased, and the mesothelium is again 
 reduced to a single layer of cells. The elevation becomes larger and projects 
 into the body cavity. At first it is attached to the mesentery (mesogas- 
 trium) by a broad, thick base, but as development proceeds the attachment 
 becomes relatively smaller and finally forms only a narrow band of tissue 
 through which the blood vessels (splenic artery and vein) pass. 
 
 Further development of the substance of the spleen consists of the break- 
 ing up of the cellular mesenchymal tissue by blood vessels and the formation 
 of the splenic corpuscles. The connective tissue trabecula, as well as the 
 
284 
 
 TEXT-BOOK OF EMBRYOLOGY 
 
 capsule of the spleen are derived from the original mesenchymal tissue. The 
 blood vessels become dilated in parts of their course to form the cavernous 
 vessels (cavernous veins) which are separated by the pulp cords. The con- 
 nective (reticular) tissue of the pulp cords is a derivative of the mesenchyme, 
 as are also the various types of cells in the cords. The adventitia of the 
 walls of some of the small arteries becomes infiltrated with lymphocytes to 
 form the splenic corpuscles (lymph follicles). 
 
 It is generally recognized that during fcetal life the spleen is a hemato- 
 
 Aorta 
 
 Omental 
 bursa 
 
 Right side 
 
 Mesonephros 
 
 Spleen 
 
 Dorsal 
 
 mesogastrium 
 (greater omentum) 
 
 Abdominal cavity 
 (coelom) 
 
 Stomach 
 Left side 
 
 Bile duct Ventral mesogastrium 
 (lesser omentum) 
 
 FIG. 259. From transverse section through stomach region of a 14 mm. 
 pig embryo. Photograph. 
 
 poietic organ, that is, both leucocytes and nucleated red blood cells are pro- 
 duced within it. Normally, the formation of erythrocytes stops at or soon 
 after birth. In severe anaemia or in pernicious anaemia in postnatal life, 
 however, the presence of dividing nucleated red blood cells suggests a return 
 to embryonic conditions. The reticular tissue constitutes the source of these 
 nucleated forms (erythroblasts) . It has also been suggested that the spleen 
 acts as a destroyer of worn-out erythrocytes, for in many cases apparent 
 remnants of the latter have been observed within the cytoplasm of the 
 
THE DEVELOPMENT OT THE VASCULAR SYSTEM 285 
 
 " spleen cells." The lymphocytes proliferate to a certain extent in the splenic 
 corpuscles, and in that way, at least, the spleen serves as a base of supply for 
 leucocytes. There is a possible suggestion that the first leucocytes of the 
 spleen have their origin in the mesenchymal cells of the spleen anlage. This 
 would be in accord with the observations which indicate that leucocytes are 
 derived from indifferent mesenchyme cells. 
 
 Mesothelium Anlage of spleen 
 \ / 
 
 Mesenchyme 
 
 -- 
 
 FiG. 260. From section through dorsal mesogastrium (anlage of spleen) of a chick embryo 
 of 3 days and 21 hours incubation. Tonkoff. 
 
 Glomus Coccygeum. 
 
 The coccygeal skein (coccygeal gland) was originally considered as belong- 
 ing to the same category as the suprarenal glands, but the latest researches 
 have indicated that its cells do not possess the characteristic chromafrin 
 reaction and that it belongs rather to the category of lymph glands. It 
 develops ventral to the apex of the coccyx in relation with branches of the 
 middle sacral artery. 
 
 Although the thymus gland becomes a lymphatic structure it is primarily 
 derived from the epithelium (entoderm) of the branchial grooves and will be 
 considered in connection with the development of the alimentary tract (Chap. 
 XII). The tonsils also will be considered in the same connection. 
 
 Anomalies. 
 
 ANOMALIES OF THE HEART. 
 
 ACARDIA. The malformation known as acardia occurs in the case of twins 
 that have but one chorion. The so-called acardiac condition does not 
 
286 TEXT-BOOK CF EMBRYOLOGY 
 
 necessarily imply the absence of the heart in the affected twin, for the latter 
 may develop to a considerable degree and possess a functionating heart. 
 On the other hand, the affected twin may be only an amorphous mass of 
 tissue which derives its total blood supply through the agency of the stronger 
 twin's heart. Or there may be any intermediate form between these two 
 extremes. The point is that the acardiac monster (acardiacus) derives its 
 blood wholly or in part through the agency of the stronger heart. A further 
 discussion of acardiac monsters and their possible explanation will be found 
 in Chap. XIX. 
 
 DOUBLE HEART. But one or two cases of a double heart in a single 
 human foetus have been recorded. In some of the lower forms (chick) it 
 occurs more frequently. The explanation is probably to be found in the 
 double origin of the heart in Amniotes (p. 227). 
 
 ANOMALOUS POSITION OF THE HEART. Congenital anomalies in the posi- 
 tion of the heart are rare. Dextrocardia (heart on the right side) is almost 
 invariably associated with changes in the position of the viscera (see trans- 
 position of the viscera, page 335). In the condition known as ectopia cordis, 
 the heart, with the pericardium, protrudes through a cleft in the ventral 
 wall of the thorax, the cleft being probably due to an imperfect fusion of the 
 two sides of the body wall in that particular region. 
 
 ANOMALIES OF THE SEPTA. The most frequent anomaly in the atrial 
 septum is the persistence of the foramen ovale. The entire foramen may 
 remain patent, or, as is more frequently the case, a smaller opening may 
 persist between the ventral (anterior) border of the foramen and the valve of 
 the latter (p. 234). 
 
 The atrial septum may be wholly lacking, but this always occurs in con- 
 junction with other defects. It sometimes happens that the primary atrial 
 septum (septum superius), which grows from the cephalic side of the common 
 chamber, fails to fuse with the septum of the a trio-ventricular aperture (p. 
 234 and Fig. 209). 
 
 Defects in the ventricular septum occur less frequently than in the atrial 
 septum. It may happen that the cephalic (upper) border of the ventricular 
 septum fails to fuse with the septum which divides the aortic trunk and bulb 
 into the aorta and pulmonary artery. This affects the cephalic (upper) part 
 of the septum sometimes called the pars membranacea (p. 235 and Fig. 212); 
 and since the defect is situated near the opening of the aorta it brings about 
 the so-called "origin of the aorta from both ventricles." Stenosis of the 
 pulmonary artery usually accompanies this condition. Rarely is there a 
 deficiency in the caudal (lower) part of the ventricular septum. Complete 
 absence of the ventricular septum may occur, and along with it also an 
 absence of the atrial septum, so that the heart is simply two-chambered; or 
 
THE DEVELOPMENT OF THE VASCULAR SYSTEM 287 
 
 the single ventricle may open into two atria. The causes of these defects 
 are obscure. 
 
 ANOMALIES OF THE VALVES, There may be congenital variations in the 
 size and number of the atrio-ventricular valves, depending upon abnormal 
 position, fusion, or division of the pad-like masses from which the valves 
 develop (p. 237). 
 
 There may be also a greater or lesser number of semilunar valves in the 
 aorta and pulmonary artery. This irregularity can probably be referred 
 back to an atypical division of the aortic trunk and bulb, and a corresponding 
 atypical division of the protuberances which give rise to the valves (p. 237). 
 Variations in the valves may or may not be accompanied by functional dis- 
 turbances. The congenital diminution in the number of valves should be 
 distinguished from the acquired, where chronic endocarditis may cause a 
 fusion. 
 
 ANOMALIES OF THE LARGE VASCULAR TRUNKS. 
 
 ANOMALIES OF THE ARTERIES. There may be a transposition of the aorta 
 and pulmonary artery. This results from an anomalous division of the aortic 
 trunk and bulb. The partition develops in such a way as to put the aorta in 
 communication with the right ventricle, and the pulmonary artery with the 
 left ventricle (p. 235). Or the aorta and pulmonary artery may remain in 
 direct communication on account of an imperfect development of the 
 partition. Rarely the two vessels remain as a common stem. 
 
 Congenital stenosis (constriction) of the pulmonary artery may occur, 
 accompanied by an increase in the size of the aorta, possibly due to an unequal 
 division of the aortic trunk and bulb. After birth little or no blood can pass 
 to the lungs, and the result is a general damming (stasis) of the venous blood 
 with marked cyanosis. This is at least one explanation of the so-called " blue 
 babies." Less frequently there is a stenosis of the proximal end of the aorta, 
 with excessive size of the pulmonary artery, also due to an unequal division 
 of the aortic trunk and bulb (p. 235). These stenoses are usually, though not 
 always, accompanied by defects in the ventricular septum. 
 
 Persistence of the ductus arteriosus may occur without any other defect; 
 but usually the persistence is associated with anomalous conditions of the 
 aorta and pulmonary artery. 
 
 Occasionally the arch of the aorta is found on the right side. This condi- 
 tion is due to the persistence of the fourth aortic arch on the right side instead 
 of the corresponding arch on the left side; this is the normal condition in 
 Birds. Rarely both fourth aortic arches persist, which results in a double 
 arch of the aorta the normal condition in Reptiles. (Compare Figs. 219 
 and 220.) 
 
288 TEXT-BOOK OF EMBRYOLOGY 
 
 The dorsal aorta, particularly the abdominal part, is occasionally found to 
 consist of two parallel, imperfectly separated vessels a condition known as 
 double aorta. This anomaly is due to an imperfect fusion of the two primitive 
 aortae (p. 218 and Fig. 203). 
 
 Numerous variations are met with in the larger branches of the aorta, 
 many of which are explained by referring them to embryonic conditions. 
 Especially noteworthy are the branches from the arch of the aorta, since their 
 development is so closely associated with the changes in the aortic arches. 
 The normal arrangement passing from the heart, is innominate artery, left 
 common carotid artery, left subclavin artery (see Fig. 220). 
 
 1. All these branches may be collected into a single trunk a condition 
 characteristic of the horse. 
 
 2. Two branches may arise from the arch, (a) The left common carotid 
 unites with the innominate, and the left subclavian arises separately. This is 
 the normal arrangement among the apes, and is probably the most common 
 variation in man. (b) Very rarely there are two innominate arteries, each 
 formed by the union of a common carotid and subclavian a condition char- 
 acteristic of Birds. 
 
 3. Three branches may arise from the arch but in a manner differing from 
 the normal. Each subclavian arises separately and the two common carotids 
 are united into a single vessel. This arrangement is found in some of the 
 Cetacea. 
 
 4. Four vessels may arise from the arch, (a) These are, in order, in- 
 nominate, left common carotid, left vertebral, left subclavian. (b) Or 
 the order may be right common carotid, left common carotid, left subclavian, 
 right subclavian. In this case the proximal part of the right subclavian rep- 
 resents the portion of the right dorsal aortic root just cranial to the bifurca- 
 tion; the fourth arch on the right side disappears, (c) Or very rarely the 
 order may be right subclavian, right common carotid, left common carotid, 
 left subclavian. 
 
 5. Five branches of the arch are rare. In order they are right sub- 
 clavian, right vertebral, right common carotid, left common carotid, left 
 subclavian. 
 
 6. Very rarely there are six branches of the arch; right subclavian, right 
 vertebral, right common carotid, left common carotid, left vertebral, left 
 subclavian. 
 
 ANOMALIES OF THE VEINS. The two pulmonary "veins on. each side, more 
 frequently those on the left side, many unite into a common trunk before 
 opening into the atrium. This variation is probably due to the fact that the 
 absorption of the originally single pulmonary trunk into the wall of the 
 
THE DEVELOPMENT OF THE VASCULAR SYSTEM 289 
 
 atrium does not proceed far enough to cause all four of the pulmonary veins 
 to open separately (see p. 236). The upper (more cephalic) vein on the right 
 side may open into the superior vena cava ; or the upper vein on the left side 
 may open into the left innominate vein. A possible explanation for this is 
 that the pulmonary veins are formed after the heart and other vessels have 
 developed to a considerable degree, and some of them may unite with the 
 other vessels instead of with the atrium. 
 
 Occasionally two superior vena cava are met with. In this case the right 
 opens into the right atrium in the normal position; the left opens into the 
 right atrium through the coronary sinus which naturally is much enlarged. 
 This condition represents a persistence of the proximal end of the left 
 anterior cardinal vein and the left duct of Cuvier, and is the normal arrange- 
 ment in many of the lower Vertebrates. Even with two venae cavae there 
 may be a small anastomosing branch in the position of the left innominate 
 vein, which represents the normal structure in the Marsupials (see Figs. 
 232 and 233 and p. 254). There are a few cases on record of a single left 
 superior vena cava. 
 
 The inferior vena cava is also subject to variations which represent the 
 abnormal persistence of certain embryonic vessels. Perhaps the most 
 striking of these variations is the condition known as double inferior vena 
 cava. There may be two parallel vessels, of equal or unequal size, which 
 unite at or above the level of the renal veins. This condition is to be ex- 
 plained by the persistence of parts of both posterior cardinal veins. It is 
 met with not infrequently among the lower Mammals, especially the Mar- 
 supials (see Figs. 233 and 236). 
 
 Rarely the inferior vena cava opens into the superior, and in this case the 
 hepatic veins open directly into the right atrium. This anomaly probably 
 represents a failure of the absorption of the sinus venosus into the wall of the 
 atrium (p. 236). 
 
 A left renal vein may open into the left common iliac, which condition 
 represents a persistence of the more caudal part of the left posterior cardinal 
 (Fig. 236). This anomaly is rare. 
 
 The azygos vein occasionally presents variations which are due to anoma- 
 lous development. All the intercostal veins on the left side may be collected 
 into a vessel which opens into the left innominate vein. There may be a 
 single median azygos vein; or there may be a transposition of the azygos vein. 
 It may be on the left side and open into the coronary sinus (normal condi- 
 tions in the sheep and a few other Mammals). The latter condition repre- 
 sents a persistence of the more cephalic part of the left posterior cardinal 
 vein (see Figs. 233 and 234). 
 
290 TEXT-BOOK OF EMBRYOLOGY 
 
 Space does not permit a discussion of the great number of congenital 
 variations that occur in the smaller blood vessels, both arteries and veins. 
 The student is referred, however, to the more extensive text-books of 
 anatomy. 
 
 References for Further Study. 
 
 BORN, G.: Beitrage zur Entwicklungsgeschichte des Saugetierherzens. Archiv f. 
 mik. Anal., Bd. XXXIII, 1899. 
 
 CLARK, E. R.: Further Observations on Living Growing Lymphatics; their Relation 
 to Mesenchymal Cells. Am. Jour, of Anat., Vol. XIII, 1911. 
 
 CLARKE, W. C.: Experimental Mesothelium. Anat. Record, Vol. VIII, 1914. 
 
 DANTSCHAKOFF, W.: Untersuchungen iiber die Entwicklung des Blutes und Bindege- 
 webes bei den Vogeln. Anat. Hefte, Bd. XXXVII, 1908. 
 
 DANCHAKOFF, V.: Origin of the Blood Cells. Development of the Haematopoetic 
 Organs and Regeneration of the Blood Cells from the Standpoint of the Monophyletic 
 School. Anat. Record, Vol. X, No. 5, 1916. 
 
 ETERNOD, A. C. F.: Premiers stades de la circulation sanguine dans 1'ceuf et embryon 
 humain. Anat. Anz., Bd. XV, 1899. 
 
 His, W.: Anatomic menschlicher Embryonen. Leipzig, 1880-1885. With Atlas. 
 
 HOCHSTETTER, F. i Die Entwickelung des Blutgefasssystems. In Hertwig's Handbuch 
 der vergleich. und experiment. Entwickelungslehre. Bd. Ill, Teil II, 1901. Contains also 
 extensive bibliography. 
 
 HOWELL, W. H.: The Life History of the Formed Elements of the Blood, Especially 
 the Red Blood-corpuscles. Journal of Morph., Vol. IV, 1890. 
 
 HUNTINGTON, G. S., and McCLURE, C. F. W.: Development of Postcava and Tribu- 
 taries in the Domestic Cat. Am. Jour, of Anat., Vol. VI, 1907. 
 
 HUNTINGTON, G. S.: The Phylogenetic Relations of the Lymphatic and Blood Vas- 
 cular Systems in Vetebrates. Anat. Record, Vol. IV, 1910. 
 
 HUNTINGTON, G. S.: The Genetic Principles of the Development of the Systemic Lym- 
 phatic Vessels in the Mammalian Embryo. Anat. Record, Vol. IV, 1910. 
 
 HUNTINGTON, G. S.: The Development of the Lymphatic System in Reptiles. Anat. 
 Record, Vol. V, 1911. 
 
 HUNTINGTON, G. S.: The Anatomy and Development of the Systemic Lymphatic 
 Vessels in the Domestic Cat. Memoirs of the Wistar Institute of Anatomy and Biology, 
 No. i, 1911. 
 
 HUNTINGTON, G. S.: The Development of the Mammalian Jugular Lymph Sac, of the 
 Tributary Primitive Ulnar Lymphatic and the Thoracic Ducts from the Viewpoint of 
 
 recent Investigations of Lymphatic Ontogeny, Am. Jour, of Anat., Vol. XVI, 
 
 No. 3, 1914. 
 
 KLING, C. A.: Studien iiber die Entwicklung der Lymphdriisen beim Menschen. 
 Archiv f. mik. Anat., Bd. LXIII, 1904. 
 
 KOLLMANN, J.: Handatlas der Entwickelungsgeschichte des Menschen, Bd. II, 1907. 
 
 LEHMAN, H.: On the Embryonic History of the Aortic Arches in Mammals 1 . Anat. 
 Anz., Bd. XXVI, 1905. 
 
 LEWIS, F. T.: The Development of the Vena Cava Inferior. Am. Jour, of Anat., 
 Vol. I, 1902. 
 
 LEWIS, F. T. : The Development of the Veins in the Limbs of Rabbit Embryos. Am. 
 Jour, of Anat., Vol. V, 1906. 
 
THE DEVELOPMENT OF THE VASCULAR SYSTEM 291 
 
 MALL, F. P. : Development of the Internal Mammary and Deep Epigastric Arteries 
 in Man. Johns Hopkins Hosp. Bull., 1898. 
 
 MALL, F. P.: On the Development of the Blood Vessels of the Brain in the Human 
 Embryo. Am. Jour, of Anat., Vol. IV, 1905. 
 
 MAXIMOW, A. : Die Friihesten Entwicklungsstadien der Blut- und Bindegewebszellen 
 beim Saugetierembryo, bis zum Anfang der Blutbildung in der Leber. Arch.f. mik. Anat. t 
 Bd. LXXIII, 1909. 
 
 MAXIMOW, A.: Lymphozyt als gemeinsame Stammzelle der verschiedenen Blutele- 
 mente in der embryonalen Entwicklung und im postfetalen Leber der Saugetiere. Folia 
 Hamatolog., Bd. VIII, 1909. 
 
 MAXIMOW, A.: Die embryonale Histogenese des Knochenmarks der Saugetiere. 
 Arch. f. mik. Anat., Bd. LXXVI, 1910. 
 
 McCLURE, C. F. W.: The Development of the Lymphatic System in Fishes with 
 Especial Reference to its Development in the Trout. Memoirs of the Wistar Institute of 
 Anatomy and Biology, No. 4, 1915. ^ 
 
 McCLURE, C. F. W., and SILVESTER, C. F.: A Comparative Study of the Lymphati- 
 co- Venous Communications in Adult Mammals. Anat. Record, Vol. Ill, 1909. 
 
 MILLER, A. M.: Histogenesis and Morphogenesis of the Thoracic Duct in the Chick;; 
 Development of Blood Cells and their Passage to the Blood Stream via the Thoracic 
 Duct. Am. Jour, of Anat., Vol. XV, 1913. 
 
 MIXOT, C. S.: On a Hitherto Unrecognized Form of Blood Circulation without Capil- 
 laries in the Organs of Vertebrata. Proc. Boston Soc. Nat. Hist., Vol. XXIX, 1900, 
 
 ROSE, C.: Zur Entwickelungsgeschichte des Saugetierherzens. Morph. Jahrbuch, Bd. 
 XV, 1889. 
 
 RUCKERT, J., and MOLLIER, S.: Die erste Entstehung der Gefasse und des Blutes bei 
 Wirbeltiere. In Hertwig's Handbuch der vergleich und experiment. Entwickelungslehre> 
 Bd. I, Teil I, 1906. Contains also extensive bibliography. 
 
 SABIN, F. R. : On the Origin of the Lymphatic System from the Veins and the Develop- 
 ment of the Lymph Hearts and Thoracic Duct in the Pig. Am. Jour, of Anat., Vol. 
 I, 1902. 
 
 SABIN, F. R. : The Origin and Development of the Lymphatic System. The Johns 
 Hopkins Hospital Reports Monographs, New Series, No. 5, 1913. 
 
 SALA, L.: Svilluppo dei cuori linfatici e dei dotti toracici nelP embrione di polio. 
 Ricerche fatte nel laboratorio de anatomia normale della R. Universita di Roma, Vol. VII, 
 1900. 
 
 SCHULTE, H. VON W.: Early Stages of Vasculogenesis in the Cat (Felis domestica) 
 with Especial Reference to the Mesenchymal Origin of Endothelium. Memoirs of the 
 Wistar Institute of Anatomy and Biology, No. 3, 1914. 
 
 STOCKARD, CHAS. R.: The Origin of Blood and Vascular Endothelium in Embryos 
 without a Circulation of the Blood and in the Normal Embryo. Am. Jour, of Anat., 
 Vol. XVIII, No. 2, 1915. 
 
 STOERK, O.: tlber die Chromreaktion der Glandula coccygea und die Beziehung 
 dieser Druse zum Nervus sympthathicus. Arch. f. mik. Anat., Bd. LXIX, 1906. 
 
 STOHR, P.: tjber die Entwicklung der Darmlymphknotchen und iiber die Riickbildung 
 von Darmdrusen. Arch. f. mik. Anat., Bd. LI, 1898. 
 
 TAXDLER, J.: Zur Entwickelungsgeschichte der menschlichen Darmarterien. Anat. 
 Heft, Bd. XXIII, 1903. 
 
 TOXKOFF, W.: Die Entwickelung der Milz bei den Amnioten. Archiv f. mik. Anat. t 
 Bd. LVI, 1900. 
 
292 TEXT-BOOK OF EMBRYOLOGY 
 
 WEIDENREICH, F. : Die Morphologic der Blutzellen und ihre Beziehungen zu einander. 
 Anat. Record, Vol. IV, 1910. 
 
 WEST, R.: The Origin and Early Development of the Posterior Lymph Heart in the 
 Chick. Am. Jour, of Anat., Vol. XVII, 1915. 
 
 WRIGHT, J. H.: The Origin and Nature of the Blood Plates. Boston Med. and Surg. 
 Jour., Vol. CLIV, 1906. 
 
CHAPTER XI 
 THE DEVELOPMENT OF THE MUSCULAR SYSTEM. 
 
 Anatomy and Histology show that there are, in a sense, two muscular 
 systems in the body, and Embryology teaches that the two systems have dif- 
 ferent origins. 
 
 1. The skeletal musculature. This, as the name indicates, is closely associated 
 with the skeletal system. It is made up of striated muscle fibers arranged to 
 form definite bundles or muscles. The skeletal musculature is under the 
 voluntary control of the central nervous system. 
 
 2. The visceral musculature. This is found in connection with and forms 
 integral parts of certain organs. It is made up of two different kinds of fibers 
 smooth muscle fibers or cells and striated fibers or cells (heart-muscle cells). 
 The latter are found only in the wall of the heart. The visceral musculature is 
 involuntary, being under the control of the sympathetic nervous system. 
 
 Both systems are derived from mesoderm but from distinct parts of the 
 mesoderm. Furthermore, their developmental histories are quite different, as 
 will be seen in the following paragraphs. 
 
 THE SKELETAL MUSCULATURE. 
 
 In the chapter on the development of the germ layers it was said (p. 72) 
 that throughout the length of the body region of the embryo the mesoderm on 
 each side of the neural tube and notochord becomes divided into a definite 
 number of segments the primitive segments or mesodermic somites (Figs. 57, 
 72, 74). These indicate the segmentation of the body, and the history of the 
 greater part of the skeletal musculature dates from their differentiation from 
 the axial mesoderm. Thus the skeletal musculature is, for the most part, 
 primarily segmental in character. 
 
 At first the primitive segments are composed of closely packed, epithelial- 
 like cells, and each segment contains a small cavity which represents a portion 
 of the coelom (Fig. 141). The ventro-medial parts of the segments become 
 differentiated to form the sclerotomes which are composed of more loosely ar- 
 ranged cells (Fig. 261), and which are destined to give rise to the vertebrae and 
 to the various kinds of connective tissue in their neighborhood. The lateral 
 parts of the segments become differentiated to form the cutis plates which are 
 destined to give rise to a part of the corium of the skin. The remaining portions 
 
 293 
 
294 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 of the segments form the muscle plates or myotomes (Fig. 261), from which 
 develop by far the greater part, at least, of the voluntary striated muscles. 
 
 The differentiation of the parts of the primitive segments begins in the cervi- 
 cal region by the end of the second week, and then gradually proceeds toward 
 the tail. Three myotomes are also probably formed in the occipital region. 
 The cells of the myotomes are at first of an epithelial character (Fig. 143). 
 Contractile fibrils appear in the cells and the latter are transformed directly 
 into muscle fibers. (For histogenesis see p. 307). The fibers later alter their 
 direction in accordance with the particular muscle to which they belong. The 
 muscle tissue first formed is thus segmented, being derived from the segmen- 
 
 Neural crest 
 
 Myotome 
 
 Myotomex 
 Scl. 
 
 '' ' ' r>>v sg-JX Sclerotome 
 
 *Z t~" * ''.r *. *r*.v 
 
 WM$k 
 
 Pronephros 
 
 ^ 
 
 Parietal mesoderm-- 
 Intestine 
 
 ""limb bud 
 
 Amnion 
 
 Visceral mesoderm - 
 
 FIG. 261. Transverse section of human embryo of the 3rd week. Sc/. 1 , Break in myotome at 
 point where sclerotome is closely attached. Kollmann. 
 
 tally arranged myotomes, but as development proceeds the myotomes undergo 
 extensive changes by which the segmental character is lost in the majority of 
 cases. It is retained, however, in a few instances, such for example as the 
 intercostal muscles. The course of the changes which obliterate the segmental 
 character of the myotomes and give rise to the various muscles has not been 
 observed in all cases. But since a nerve belonging to any particular segment 
 and innervating the myotome of that segment always innervates the muscles 
 derived from that myotome, it is possible to learn something of the history of 
 the myotomes by studying the innervation of the muscles. 
 
 From a consideration of what is known concerning the individual histories 
 
THE DEVELOPMENT OF THE MUSCULAR SYSTEM. 295 
 
 of the muscles and concerning the innervation of the muscles, certain factors 
 can be recognized, to one or more of which the changes in the myotomes may 
 be referred. These factors are as follows: 
 
 1. Migration. The myotomes may migrate in whole or in part, and the 
 muscles derived from them may be situated far beyond their limits. For 
 example, the latissimus dorsi is derived from cervical myotomes but ultimately 
 becomes attached to the lumbar vertebrae and to the crest of the ilium. To this 
 factor, possibly more than to any other, is due the loss of the segmental character 
 in the musculature. 
 
 2. Fusion. Portions of two or more myotomes may fuse to form one muscle. 
 For example, each oblique abdominal muscle is derived from several thoracic 
 myotomes. 
 
 3. Longitudinal Splitting. Very frequently a myotome or a developing 
 muscle splits longitudinally into two or more portions. The sternohyoid and 
 the omohyoid, for example, are formed in this manner. 
 
 4. Tangential Splitting. A developing muscle may split tangentially into 
 two or more plates or layers. The two oblique and the transverse abdominal 
 muscles, for example, are formed in this way. 
 
 5. Degeneration. Myotomes may degenerate as a whole or in part and be 
 converted into some form of connective tissue, such as fascia, ligament or 
 aponeurosis. The aponeuroses of the transverse and oblique abdominal 
 muscles are probably due to a degeneration of portions of the myotomes from 
 which the muscles are derived. 
 
 6. Change of Direction. The muscle fibers may change their direction. 
 As a matter of fact, the fibers of very few muscles retain their original direction. 
 
 Muscles of the Trunk. 
 
 The myotomes are at first arranged serially along each side of the notochord and 
 spinal cord (compare Fig. 262 with Figs. 143 and 261) . By the end of the second 
 week fourteen myotomes are differentiated in the human embryo. Differen- 
 tiation continues until, by the end of the fourth week, the total number thirty- 
 eight is present. Of the thirty-eight, three are occipital, eight cervical, twelve 
 thoracic, five lumbar, five sacral, and five (or six) coccygeal. The occipital 
 myotomes are transient structures that appear in relation with the hypoglossal 
 (XII) nerve. The cervical, thoracic, lumbar, sacral and coccygeal myotomes 
 correspond individually to the spinal nerves (Fig. 262). As stated on page 180, 
 the myotomes alternate with the anlagen of the vertebrae. Consequently in the 
 cervical region there are eight myotomes, corresponding to the eight cervical 
 spinal nerves, and only seven vertebrae. The myotomes in the neck and body 
 regions are destined to give rise to the dorsal musculature, to the thoraco- 
 
296 TEXT-BOOK OF EMBRYOLOGY. 
 
 abdominal musculature, to a part of the muscles of the neck, and to the 
 muscles of the tail region. There is a possibility that they give rise also to the 
 muscles of the tongue. 
 
 As the myotomes continue to develop, they become elongated in a ventral 
 
 FIG. 262. Lateral view of human embryo of 9 mm. (4^ weeks). Bardeen and Lewis. 
 
 The area from which the skin has been removed is drawn from reconstructions. The myotomes 
 have fused to a certain extent, so that segmentation is becoming less distinct. Note that the 
 myotomes correspond to the spinal nerves. The developing muscle mass (the myotomes 
 collectively) extends ventrally in the body wall in the thoracic region, and is divided by a 
 longitudinal groove into two parts a dorsal and a ventro-lateral (see text). 
 
 In the region of the upper extremity, dense masses of " premuscle " tissue are represented which 
 later form the muscles. In the region of the forearm and hand the " premuscle " tissue has 
 been removed to disclose the anlagen of the skeletal elements (radius, ulna, and hand plate). 
 In the region of the lower extremity the superficial tissue has been removed to disclose the 
 border vien, the anlagen of the os coxae, and the lumbo-sacral nerve plexus. 
 
 direction. Those of the thoracic region extend into the connective tissue of 
 the somatopleure, or in other words, into the lateral body walls (compare 
 Figs. 262 and 263). During the fifth week the myotomes give rise to a dorso- 
 ventral mass of developing muscle tissue, in which the segmental character 
 
THE DEVELOPMENT OF THE MUSCULAR SYSTEM. 
 
 297 
 
 Spinal ganglion .../; 
 
 Dorsal musculature 
 
 Ventro-lateral 
 musculature 
 
 >^ Vertebral arch 
 Dorsal ramus of 
 spinal nerve 
 
 Segmental artery 
 
 Costal process 
 
 Lat. branch of 
 spinal nerve 
 
 Vent, branch of 
 spinal nerve 
 
 FIG. 263. Diagrammatic cross section through the 5th-6th thoracic segments of a human embryo 
 of 9 mm. (4^ weeks). Bardeen and Lewis. 
 
 FIG. 264. Drawing from a reconstruction of the region of the lower extremity of a human embryo 
 of 9 mm. (4^ weeks). Bardeen and Lewis. 
 
 The visceral organs and the greater part of the left body wall have been removed. The 8th thoracic 
 to the 5th sacral segments are shown. On the right side of the body the costal processes, 
 the spinal nerves (including the lumbo-sacral plexus), and the lower extremity are shown. 
 On the left side the costal processes, the spinal nerves, and the nth and i2th thoracic myo- 
 tomes are represented. Note the dorsal, lateral, and sympathetic branches of the spinal 
 nerves. 
 
298 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 largely disappears. The muscle mass then becomes divided longitudinally 
 into two parts, (i) a dorsal and (2) a ventro-lateral (Figs. 262, 263 and 264). 
 
 1. The dorsal part is destined to give rise to those dorsal muscles of the 
 trunk that are not associated with the extremities, and is innervated by the 
 dorsal rami of the spinal nerves (Fig. 263). 
 
 2. The ventro-lateral part again divides longitudinally into (a) a lateral 
 
 External oblique 
 
 External inteicostal 
 
 Internal intercostal I Ventro-lateral 
 
 Internal oblique | musculature 
 
 Transversalis 
 
 Rectus 
 
 FIG. 265. Diagrammatic cross section through the 6th-yth thoracic segments of a human embryo 
 of 17 mm. (5^ weeks). Bardeen and Lewis. 
 
 and (b) a ventral part, although the line of division is not so distinct as 
 between the original (i) dorsal and (2) ventro-lateral parts (Fig. 265). 
 
 (a) The lateral part subdivides tangentially and gives rise in the cervical 
 region to the longus capitis, longus colli, rectus capitis anterior, to the 
 scaleni, and to parts of the trapezius and sternomastoideus (Figs. 266 
 and 267). In the thoracic region it gives rise to the intercostales 
 and to the transversus thoracis (Figs. 265 and 268) ; in the abdominal 
 region to the psoas, quadratus lumborum, and to the obliqui and 
 transversus abdominis (Figs. 267 and 268). 
 
THE DEVELOPMENT OF THE MUSCULAR SYSTEM. 299 
 
 (b) The ventral part gives rise in the cervical region to the sternohyoideus, 
 omohyoideus, sternothyreoideus and geniohyoideus. In the abdominal 
 region the ventral part gives rise to the rectus abdominis and to the 
 pyramid alls (Figs. 265 and 267). In the thoracic region there are no 
 muscles derived from the ventral part, corresponding to those in the 
 abdominal region. This is probably due to the development of the 
 sternum. 
 
 FIG. 266. Lateral view of a human embryo of u mm. (about 5 weeks). Bardeen and Lewis. 
 The area from which the skin has been removed is drawn from reconstructions. The dorsal mus- 
 culature has been removed from the region of the upper extremity, exposing the 4th to the 
 8th cervical and the ist to the 3d thoracic vertebrae. The dorsal musculature has likewise 
 been removed from the 5th lumbar and first three sacral segments. Segmentation is practi- 
 cally lost in the dorsal musculature in the thoracic region, but is still evident in the lumbar, 
 sacral and coccygeal regions. The ventro-lateral musculature is distinctly separated from the 
 dorsal, and is beginning to differentiate into the muscles of the thorax and abdomen. 
 
 The ventro-lateral portions of the lumbar myotomes and of the first two 
 sacral myotomes, corresponding to the ventro-lateral portions of the thoracic 
 myotomes, apparently do not take part in the production of muscles w r hich be- 
 long to the body wall proper. It is even questionable whether they give rise to 
 any muscles of the lower extremities. The ventro-lateral portions of the third 
 
300 TEXT-BOOK OF EMBRYOLOGY. 
 
 and fourth sacral myotomes give rise to the levator ani, the coccygeus, the 
 sphincter ani eocternus and the perineal muscles. The dorsal parts of the myo- 
 tomes as far as the fifth sacral probably give rise to the sacrospinalis (Fig. 266). 
 THE DIAPHRAGM. In addition to certain structures which are considered 
 in connection with the pericardium (parietal mesoderm, mesocardium and 
 common mesentery Chapter XIV), two myotomes on each side enter into 
 
 FIG. 267. Drawing from a reconstruction of a human embryo of 20 mm. (about 7 weeks). 
 
 Bardeen and Lewis. 
 
 The superficial tissues have been removed from the extremities, the body wall, and the back. 
 
 the formation of the diaphragm. These are the third and fourth cervical myo- 
 tomes, parts of which grow into the developing diaphragm in the earlier stages 
 when it is situated far forward in the cervical region (p. 378 and Fig. 336), and 
 give rise to its muscular elements. 
 
 Muscles of the Head. 
 
 Primitive segments (mesodermic somites) are not clearly demonstrable in 
 the heads of human embryos, nor, in fact, in the heads of any of the higher 
 Vertebrates. In some of the lower forms, however, they are very distinct. It 
 seems possible, even probable, that their indistinctness in the higher animals 
 
THE DEVELOPMENT OF THE MUSCULAR SYSTEM. 
 
 301 
 
 is due to an abbreviation or condensation in the development of the head 
 region. Such condensations are known to occur in the development of other 
 structures. In a human embryo 3.5 mm. long, three structures resembling 
 segments have been seen somewhat caudal to the region of the ootic vesicle on 
 
 FIG. 268. Drawing from a reconstruction of the right side of a human embryo of 20 mm. (about 
 
 7 weeks). Bardeen and Lewis. 
 
 The left body wall and viscera have been removed. Note especially the following muscles: The 
 deltoid and biceps, just to the left of the brachial plexus and below the clavicle; the internal 
 intercostals; the diaphragm, attached to the body wall; the transverse abdominal and the 
 rectus abdominis; the quadratus lumborum, just to the right of the transverse abdominal; 
 the psoas, cut just above the lumbo-sacral plexus; the levator ani, running obliquely upward 
 from the coccygeal region. 
 
 one side. On the other side there were seven similar but smaller structures. 
 All were composed of epithelial-like cells surrounding small cavities. 
 Whether these segment-like structures bear any relation to the mesenchymal 
 condensations which appear regularly in the occipital region (p. 189), seems 
 not to have been determined. 
 
302 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 Although the transformation of head segments into muscles has not been 
 followed in detail in mammalian embryos, it may be inferred from the study of 
 lower forms that three segments are involved in the formation of the eye muscles. 
 The most cephalic (anterior) segment gives rise to the recti superior, inferior 
 and medialis (internus) and to the obliquus inferior , all of which are innervated 
 by the occulomotor (III) nerve. The next segment gives rise to the obliquus 
 superior which is innervated by the pathetic (IV) nerve. The most caudal 
 segment gives rise to the rectus lateralis (externus) which is innervated by the 
 abducens (VI) nerve. 
 
 The development and innervation of the other muscles of the head and of 
 the hyoid musculature present certain peculiarities which have caused these 
 muscles to be considered as more closely related to the visceral musculature 
 than to the myotomic musculature. In the first place they are derived from 
 
 Eighth cervical 
 myotome 
 
 Upper limb 
 bud 
 
 Somatcpleure 
 
 Mesonephric 
 duct 
 
 FIG. 269. Transverse section through the eighth cervical segment of a human 
 embryo of 2.1 mm. Lewis. 
 
 the branchial arches (hence are often called branchiomeric muscles}, and not 
 directly from the myotomes of the neck region. This places them in closer 
 relation to the visceral muscles, although they are structurally and functionally 
 different from the latter. In the second place the nerves which supply them 
 are fundamentally different from those which supply the myotomic muscles 
 (Chap. XVII). 
 
 The first branchial arch on each side gives rise to the temporalis, masseter 
 and pterygoidei, to the mylohyoideus and digastricus (venter anterior) and to the 
 tensor tympani and tensor veli palatini. All these muscles are innervated by the 
 trigeminal (V) nerve. 
 
 The second arch, which is often called the hyoid arch, gives rise to a large 
 sheet of myogenic tissue which produces many of the facial muscles, such as the 
 
THE DEVELOPMENT OF THE MUSCULAR SYSTEM. 303 
 
 platysma and epicranius, the muscles of expression quadratus labii superioris, 
 risorius, triangularis, mentalis, etc.; also two muscles connected with the hyoid 
 bone digastricus (venter posterior) and stylohyoideus and the stapedius of the 
 middle ear. The facial (VII) nerve corresponds to the second arch and sup- 
 plies all these muscles. 
 
 The glossopharyngeal (IX) nerve corresponds to the third branchial arch, 
 and this fact indicates the muscles derived from that arch. Some, at least, of 
 the constrictor muscles of the pharynx are derived from the third arch. The 
 stylo-pharyngeus is also a derivative of the same arch. 
 
 The vagus (X) nerve is associated with the fourth and fifth arches and con- 
 sequently innervates the muscles derived from these arches, viz., the rest of the 
 constrictors of the pharynx (see above), the laryngeal muscles and the muscles 
 of the soft palate (except the tensor veli palatini which is derived from the first 
 arch (p. 302) . The glossopalatinus and chondroglossus are also derived from 
 the fourth and fifth arches, while the rest of the extrinsic muscles of the tongue 
 are of myotomic origin. 
 
 Two other muscles are probably derived in part from the branchial arches, 
 for fibers of the spinal accessory (XI) nerve afford a part of their innervation. 
 These are the trapezius and the sternomastoideus, the remaining parts of which 
 are of myotomic origin (p. 298). 
 
 Muscles of the Extremities. 
 
 The question as to whether the muscles of the extremities are derivatives of 
 the myotomes or of the mesenchymal tissue in the limb buds has not been 
 settled. In some of the lower Vertebrates, especially in some of the Fishes, it 
 seems to have been pretty clearly demonstrated that bud-like processes from 
 the myotomes grow into the anlagen of the extremities (fins), and there give 
 rise to muscles. In other lower forms no such buds from the myotomes have 
 been demonstrated, but the muscles are apparently derived directly from 
 the mesenchymal tissue in the anlagen of the extremities. In the higher verte- 
 brates, especially in Mammals, no distinct myotome buds have been traced into 
 the extremities. Some investigators hold, however, that instead of myotome 
 buds some cells from the myotomes myoblasts wander into the limb buds 
 and give rise to muscles. Other investigators are inclined to the view that the 
 musculature of the extremities is not of myotomic origin, but that it is derived 
 from the mesenchymal tissue of the limb buds. 
 
 A most striking feature of the musculature of the extremities is its distinctly 
 segmental nerve supply. This, of course, is in favor of, although it does not 
 prove, its myotomic origin. If the muscles of the extremities are of myotomic 
 origin, it is very probable that several myotomes take part in their formation. 
 
304 TEXT-BOOK OF EMBRYOLOGY. 
 
 In the first place among the lower Vertebrates the muscles of each extremity are 
 derived from several myotomes and are innervated by segmental nerves cor- 
 responding to these myotomes. In the second place among the higher Verte- 
 brates, although the myotomic origin of the muscles has not been clearly demon- 
 strated, the nerve supply in each extremity comes through several segmental 
 spinal nerves. 
 
 Knowledge concerning the development of the individual muscles of the ex- 
 tremities in the human embryo is incomplete. Especially is this true of the 
 muscles of the lower extremities. 
 
 The upper limb bud first appears in embryos of 2-3 mm. (during the third 
 week) as a slight swelling ventro-lateral to the myotomes in the lower cervical 
 
 Eighth cervical / 
 
 myotome /,".' 
 
 Upper limb bud 
 
 Border vein 
 
 FIG. 270. Transverse section through the eighth cervical segment of a human 
 embryo of 4.5 mm. Lewis. 
 
 region (Fig. 269; see also Fig. 123). The swelling gradually enlarges and by 
 the time the embryo has reached a length of 4-5 mm. lies op'posite the last four 
 cervical and the first thoracic myotomes. At this time it is filled with closely 
 packed mesenchymal cells. No buds from the myotomes can be seen extending 
 into the mesenchyme (Fig. 270). 
 
 In succeeding stages the limb bud enlarges still more, and the mesenchymal 
 tissue becomes denser (Figs. 271 and 272). During these stages no growths, 
 either of buds or of individual cells, from the myotomes are apparent. Some 
 of the cervical nerves, however, enter the limb buds (Fig. 272). 
 
 Apparently the tissue from which the muscles, as well as the skeletal ele- 
 ments, are to develop, is the condensed mesenchymal tissue. The first indica- 
 tion of differentiation occurs during the fourth week (embryo of about 8 mm.). 
 The central portion or core of the mesenchymal mass becomes still denser to 
 form the anlage of the skeletal elements of the extremity. The tissue of the 
 
THE DEVELOPMENT OF THE MUSCULAR SYSTEM. 
 
 305 
 
 core shades off into the surrounding tissue of a lesser density, which is destined 
 to give rise to the muscles and which is known as the premusde sheath. 
 
 During these processes of differentiation in the limb bud proper, masses of 
 premuscle tissue have also become differentiated around the base of the limb 
 bud. These are the forerunners of certain extrinsic muscles of the upper ex- 
 tremity, such as the pectoralis, levator scapula, trapezius, latissimus dorsi, ser- 
 ratus, etc. (Fig. 273; compare with Fig. 274). 
 
 Spinal ganglion 
 
 Intervertebral disk 
 
 8th cervical 
 myotome 
 
 Upper 
 limb bud 
 
 Border vein 
 
 FlG. 271. Transverse section through the 8th cervical segment of a human 
 embryo of 5 mm. Lewis. 
 
 By the end of the fifth week the premuscle sheath in the limb bud proper be- 
 comes more or less differentiated into muscles or groups of muscles. The 
 differentiation is most complete at the proximal end. From this the transition 
 is gradual to the distal end where the premuscle sheath is intact 
 
 By the end of the sixth week most of the muscles of the upper extremity are 
 recognizable (Figs. 274 and 275). 
 
 By the end of the seventh week practically all the muscles can be recognized 
 and are composed of muscle fibers. 
 
 During the differentiation of the muscles, the limb bud and certain ex- 
 trinsic muscles migrate a considerable distance caudally. For example, the 
 
306 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 pectoralis and latissimus dorsi migrate from the base of the arm to the thoracic 
 wall. Their nerves are naturally pulled with them. The trapezius muscle, 
 which originates well forward in the cervical region, migrates so that it finally 
 reaches as far as the last thoracic vertebra. The sternomastoideus also origi- 
 nates well forward in the cervical region, but finally extends to the clavicle and 
 sternum. The migration of the upper extremity causes the brachial plexus to 
 have a caudal inclination. 
 
 The lower limb buds arise very soon after the upper. As stated on page 153, 
 the upper limbs always maintain a slight advance over the lower in develop- 
 
 Spinal ganglion 
 
 Vertebral arch 
 
 8th cerv. myotome 
 
 8th cerv. nerve 
 6th, 7th cerv. nerv 
 Condensed 
 mesenchyme 
 
 Border vein 
 
 Somatopleure 
 
 FlG. 272. Transverse section through the 8th cervical segment of a human 
 embryo of 7 mm. (about 4 weeks). Lewis. 
 
 ment. As in the case of the upper, the lower limb buds appear as swellings on 
 the ventro-lateral surface of the body, opposite the fifth lumbar and first sacral 
 myotomes. The interior of each swelling is at first composed of closely packed 
 mesenchymal tissue, but whether any part of the myotomes enters it is question- 
 able. At all events several spinal nerves do enter the tissue and supply the 
 muscles. The differentiation of a central core as the anlage of the skeleton, and 
 the differentiation of the surrounding tissue as the premuscle sheath, take place 
 in the same manner as in the upper extremity (p. 305) . From this premuscle 
 sheath all the muscles of the lower extremity are developed. 
 
THE DEVELOPMENT OF THE MUSCULAR SYSTEM. 307 
 
 Histogenesis of Striated Voluntary Muscle Tissue. 
 
 The majority of the striated voluntary muscles of the body are derived from 
 the myotomes. Some are derived from the mesenchymal tissue in the branchial 
 arches, some possibly from the mesenchymal tissue in the limb buds. The 
 primitive segments are at first composed of closely arranged, epithelial-like cells 
 that radiate from a small centrally placed cavity (Fig. 141). The cavity repre- 
 sents part of the ccelom and from this point of view it can be said that the muscle 
 is a derivative of the epithelial lining of the coelom. A part of each primitive 
 
 Scapular 
 
 Pectoral 
 
 "Premuscle" 
 
 Border vein 
 
 5th nerve 
 
 Phrenic nerve 
 Brachial plexus 
 
 Sympathetic 
 
 Diaphragm 
 
 Vertebra 
 
 Hand plate 
 
 4th rib 
 
 FIG. 273. Drawing from a reconstruction of the upper limb region of a human 
 
 embryo of 9 mm. (4^ weeks) ; ventral view. Lewis. 
 
 Inf. hy., infrahyoid; Lev. scap., levator scapulae; My., myotome mass; Rhom., 
 rhomboid; Trap., trapezius. 
 
 segment becomes the sclerotome and cutis plate. The remaining part be- 
 comes the myotome or muscle plate (Fig. 261). 
 
 The cells of the myotome are at first not essentially different from those of 
 the rest of the primitive segment. Soon, however, changes take place in them 
 and they become the so-called myoblasts or muscle-forming cells, which are 
 destined to give rise to the muscle fibers. Opinions differ as to the manner in 
 which the myoblasts produce the muscle fibers. It was once thought that each 
 myoblast gave rise to a single muscle fiber in which there were several nuclei, all 
 
308 TEXT-BOOK OF EMBRYOLOGY. 
 
 derived from the original myoblast nucleus by mitotic division. It was also 
 thought that the muscle fibrillae represented highly modified and specialized 
 parts of the cytoplasm, which arranged themselves longitudinally in the cell. 
 Some of the later researches indicate that a muscle fiber represents a number of 
 myoblasts fused together. This explanation is not, however, accepted by all 
 investigators. 
 
 In contrast with the above, there is a quite general consensus of opinion in 
 regard to the development of the internal structure of the muscle fiber. In the 
 
 FIG. 274. Lateral view of a reconstruction of the muscles of the upper extremity of a human 
 embryo of 16 mm. (about 6 weeks). Lewis. 
 
 The trapezius is the large muscle arising from the transverse processes of the vertebrae (at the right 
 of the figure) and converging to its insertion on the clavicle. Just below the insertion of the 
 trapezius is the deltoid, which partly hides the subscapular (on the right) and the pectoralis 
 major (on the left). Arising beneath the deltoid and running downward to the elbow is the 
 triceps. To the right of the triceps is the teres major (composed of two parts). The large 
 sheet of muscle extending down the forearm and sending divisions to the 2d, 30!, 4th and 5th 
 digits is the extensor communis digitorum. 
 
 cytoplasm of the myoblasts there appear granules which soon arrange them- 
 selves in parallel rows and unite to form slender thread-like fibrils (Fig. 276). 
 These fibrils are at first confined to one myoblast area. If several myoblasts 
 fuse, the fibrils probably extend in a short time from one myoblast area to 
 another. If one myoblast produces a fiber, the fibrils naturally are confined to 
 a single myoblast area throughout development. The fibrils are usually 
 formed first at the periphery of the cell and later in the interior (Figs. 277 
 
THE DEVELOPMENT OF THE MUSCULAR SYSTEM. 309 
 
 and 278.) At the same time they increase in number by longitudinal splitting. 
 The cytoplasm among the fibrils becomes the sarcoplasm. 
 
 After the granules which first appear unite to form the fibrils, the latter 
 
 FIG. 275. Medial view of a reconstruction of the muscles of the upper extremity of a human 
 embryo of 16 mm. (about 6 weeks). Lewis. 
 
 The muscle arising on the scapula (at the left of the figure) and passing toward the right is the 
 subscapular. The small muscle just below the subscapular is the teres major; below the 
 latter and hanging downward is the latissimus dorsi. Note the cut end of the pectoralis 
 minor just to the right of the narrow portion of the subscapular. Running from this cut end 
 toward the right is the biceps. The muscle at the lower edge of the figure in the arm region 
 is the triceps. In the forearm region, the muscle crossing the end of the biceps is the pro- 
 nator teres. Below the pronator teres, extending from the elbow to the thumb region is the 
 flexor carpi radialis. Below the latter and extending to a point opposite the thumb, is the 
 palmaris longus. Beneath the palmaris longus and dividing into branches which pass to the 
 sd, 3d, 4th, and 5th digits is the flexor sublimis digitorum. The muscle passing to the 
 thumb is the flexor longus pollicis. The muscle at the lower border of the figure in the fore- 
 arm region is the flexor carpi ulnaris. 
 
 
 FIG. 276. Myoblasts in different stages of development. Godlewski. 
 
 The upper cell represents a myoblast with granular cytoplasm (from sheep embryo of 13 mm) ; the 
 middle, a myoblast with fibrils in process of formation (from guinea-pig embryo of 10 mm.); 
 the lower, a myoblast with still further differentiated, segmented fibrils (from a rabbit 
 embryo of 8.5 mm.). 
 
 are apparently quite homogeneous. Later they become differentiated into two 
 distinct substances which alternate throughout their length and produce the 
 
310 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 characteristic cross striation. The nature of this differentiation is not known. 
 One investigator holds that both substances are derived from the original 
 granules that unite to form the fibrils, alternate granules being composed of like 
 substance and united by delicate strands of the other substance. 
 
 While the fibrils are being formed, the nuclei of the myoblasts undergo rapid 
 mitotic division. When the cells are about filled with fibrils, the nuclei migrate 
 to the periphery where they are situated in the fully formed fiber (Fig. 278). 
 Each fiber thus possesses a number of nuclei, whether it is derived from one 
 myoblast or from several. 
 
 A.. 
 
 x-T^rx / I ^*V?) 7 
 
 /$&&. \\ : Sy.^~^<, // fj rU^// > ^S>*/ 
 
 
 FIG. 278 
 
 FIG. 277. From a cross section of developing voluntary striated muscle in the leg of a pig embryo 
 
 of 45 mm., showing fibril bundles at the periphery of the cells. MacCallum. 
 FIG. 278. From a cross section of developing voluntary striated muscle in the leg of a pig embryo 
 
 of 75 mm., showing fibril bundles more numerous than in Fig. 277. A, Central vesicular 
 
 nucleus; B, peripheral more compact nucleus. MacCallum. 
 
 For some time at least, the number of fibers in a developing muscle increases 
 by division of those already formed. This process would produce a certain 
 degree of enlargement of the muscle as a whole. Later the increase in the 
 number of fibers ceases, and the muscle grows by enlargement of the individual 
 fibers. It is not certain at what period in development the increase in the num- 
 ber of fibers ceases. 
 
 In many muscles development is further complicated by a retrograde proc- 
 ess a degeneration of some of the fibers. This occurs quite regularly in the 
 extremities. A well fibrillated fiber first presents a homogeneous appearance, 
 then becomes vacuolated, the nuclei disintegrate, and finally the whole 
 structure disappears. Mesenchymal (or connective) tissue takes its place, and 
 the remaining fibers are thus grouped into bundles and the bundles into 
 muscles. This would account to a certain extent for the intermuscular con- 
 
THE DEVELOPMENT OF THE MUSCULAR SYSTEM. 
 
 311 
 
 nective tissue, the perimysium and endomysium, the epimysium being derived 
 from the mesenchymal tissue which originally surrounded the muscle. 
 
 THE VISCERAL MUSCULATURE. 
 
 The visceral musculature is derived wholly from the mesoderm, but not 
 from the myotomes. The striated involuntary muscle or heart muscle is de- 
 rived from the mesothelial lining of the coelom, the smooth muscle from the 
 mesenchymal tissue in various regions of the body. The heart muscle develops 
 only in connection with the heart and consequently occurs in the adult only in 
 that organ. Smooth muscle develops to form integral parts of certain structures 
 such, for example, as the alimentary tube, glands, blood vessels, and skin. 
 
 Histogenesis of Heart Muscle. 
 
 When the simple tubular heart is first formed, the splanchnopleure projects 
 into the ccelom (primitive pericardial cavity) along each side (Fig. 203; also p. 
 227). The mesothelium covering these projections is destined to give rise to 
 
 FIG. 279. From a section of developing heart muscle from a rabbit embryo of 9 mm. Godlewski. 
 
 a, Cell body with granules arranged in series; b, cell body with centrosome and attraction sphere; 
 
 c, branching fibril; d, fibrils extending through several cells. 
 
 the myocardium. The mesothelial cells which are at first closely packed to- 
 gether with but little intercellular substance, assume irregular branching forms 
 and the branches anastomose freely (Fig. 279). After the cells become loosely 
 arranged, they again become closely packed to form a compact syncytium, in- 
 dividual cells apparently assuming the shape of heavy bands (Fig. 280). Ir- 
 regular transverse bands next appear, dividing the syncytium into the so-called 
 
312 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 Heart muscle cells. These may or may not represent the original cells or 
 myoblasts. At all events the muscle fibrils are continuous across the lines. 
 The nuclei proliferate in the syncytium but remain in the central part of the 
 bands or cells, instead of migrating to the periphery as in striated voluntary 
 muscle. 
 
 While the cells are still loosely arranged, rows of granules appear in the 
 cytoplasm, and the granules in each row unite to form a fibril (Fig. 279) . The 
 
 fibrils are at first confined to individual 
 cell areas, but as the cells come closer 
 together to form the compact syncytium, 
 they extend through several cell areas 
 and run in different directions (Fig. 280) . 
 As development proceeds the fibrils be- 
 come more nearly parallel (Fig. 281). 
 They are first formed in the peripheries 
 of the cells, but later also in the interior, 
 except in a small area immediately sur- 
 rounding the nucleus, where a small 
 amount of undifferentiated cytoplasm 
 remains. The latter is continuous 
 with the cytoplasm or sarcoplasm 
 among the fibrils. As in voluntary 
 striated muscle the fibrils become differ- 
 entiated into two distinct substances 
 which alternate with each other, thus 
 producing the transverse striation. 
 
 FlG. 280. From a section of developing 
 heart muscle in a rabbit embryo of 9 mm. 
 Godlewski. 
 The cells form a compact syncytium. 
 
 Histogenesis of Smooth Muscle. 
 
 The mesenchymal cells which are destined to produce smooth muscle cells 
 are not grouped into any particular primitive structures like the mesodermic 
 somites. They are simply scattered through the general mass of mesenchymal 
 tissue and, like other mesenchymal cells, possess irregular branching forms and 
 distinct spherical nuclei. The internal changes by which these cells are con- 
 verted into muscle cells are not well known. The contractile elements 
 the fibrillae probably represent highly modified portions of the original cyto- 
 plasm but the manner in which the cytoplasm is transformed into fibrillae has 
 not been determined. The external changes consist essentially in an elonga- 
 tion of the irregular mesenchymal cells. The result of this elongation is usually 
 a spindle-shaped cell, but exceptionally cells forked at one or both ends are 
 produced. The original spherical nucleus also shares in the elongation and 
 becomes rod-shaped. 
 
THE DEVELOPMENT OF THE MUSCULAR SYSTEM. 
 
 313 
 
 In some cases, for example in the muscular layers of the gastrointestinal 
 tract, distinct bands or sheets of smooth muscle are formed in which the cells 
 are closely packed and lie approximately parallel. In other cases, such as the 
 mucosa of the intestine and the capsules of certain glands, the muscle cells 
 develop in little groups or as isolated cells. 
 
 Anomalies. 
 
 More or less of the muscular system is involved in some of the gross anoma- 
 lies or malformations of the body. For example, congenital defects in the cen- 
 tral nervous system (anencephaly, rachichisis, etc.) are necessarily accompanied 
 by atrophy or faulty development of certain parts of the muscular system. In 
 the case of ventral median fissure of the abdominal wall (gastroschisis) , the 
 
 FIG. 281. From a section- of developing heart muscle in a rabbit embryo of 10 mm. Godlewski. 
 The fibrils are segmented, indicating the beginning of the cross striation characteristic of heart muscle. 
 
 abdominal muscles are naturally involved. Such anomalies in the muscles are, 
 however, secondary to the other malformations and are not due to primary 
 defects in the muscles themselves. 
 
 Many of the minor variations in the muscular system occur in the same 
 form or in similar forms in different individuals, thus indicating their relation to 
 a fundamental type. Many of these are more or less accurate repetitions of 
 normal structures found in lower animals. Such variations are probably 
 rightly attributed to hereditary influences. On the other hand, there are varia- 
 tions which cannot be referred to conditions found in any of the lower animals. 
 These constitute a class of variations which must be accounted for upon some 
 other basis than that of heredity. As pointed out in the chapter on Teratogene- 
 sis (Chap. XIX), external influences undoubtedly play an important part in the 
 production of anomalies and it is probable that similar influences act upon the 
 development of the muscular system. 
 
 The scope of this book does not permit a description, or even mention, of the 
 great number of variations in the muscles. A few are described here as ex- 
 
314 TEXT-BOOK OF EMBRYOLOGY. 
 
 amples; for others the student is referred to the more extensive text-books of 
 anatomy. 
 
 EXTRINSIC MUSCLES OF THE UPPER EXTREMITY. The trapezius is some- 
 times attached to less than the normal number of thoracic vertebrae. Its 
 occipital attachment may be wanting. Occasionally the cervical and thoracic 
 portions are more or less separated as in some of the lower animals. 
 
 The latissimus dorsi sometimes arises from less than the usual number of 
 thoracic vertebrae, and from less than the normal number of ribs. The iliac 
 origin may be wanting. 
 
 The rhomboidei vary in their vertebral and scapular attachments. 
 
 The number of the vertebral attachments of the levator scapulae may vary. 
 A small part of the muscle is sometimes attached to the occipital bone. 
 
 The pectoralis major not infrequently varies in the extent of its attachment 
 to the ribs and sternum. 
 
 The serrati vary in their attachment to the ribs. 
 
 The above mentioned extrinsic muscles of the upper extremity vary prin- 
 cipally in their attachments. Since they all appear well forward in the cervical 
 region in the embryo, and, along with the extremity, gradually migrate caudally 
 before acquiring their final attachments, it is not unlikely that the variations in 
 their attachments are due to variations in the extent of migration. 
 
 This serves to illustrate a factor which is probably important in producing 
 variations in the attachments of many other muscles. As stated in paragraph 
 i, on page 295, the myotomes frequently migrate very extensively during 
 their transformation into muscles, before the muscles have acquired their per- 
 manent attachment. Variations in the extent of this migration would naturally 
 produce variations in the final attachments of these muscles. 
 
 Other factors related to the changes in the myotomes, such as fusion, longi- 
 tudinal and tangential splitting (paragraphs 2, 3 and 4, p. 295) probably also 
 play a part in the production of variations. 
 
 A greater than normal degree of fusion between two or more myotomes 
 might result in the union of muscles which are usually separate; a less than 
 normal degree of fusion might result in the separation of parts usually united. 
 Variations in the splitting of myotomes might produce similar results. 
 
 At the same time, however, heredity may be the active factor in some cases 
 where abnormal fusions or separations between muscles or parts of muscles 
 produce results resembling conditions found in lower animals. 
 
 Reference for Further Study. 
 
 BARDEEN, C. R.: The Development of the Musculature of the Body Wall in the Pig, 
 Including its Histogenesis and its Relation to the Myotomes and to the Skeleton and to the 
 Nervous Apparatus. Johns Hopkins Hospital Reports, Vol. XI. 
 
THE DEVELOPMENT OF THE MUSCULAR SYSTEM. 315 
 
 BARDEEX, C. R., and LEWIS, W. H.: Development of the Limbs, Body Wall and Back 
 in Man. American Jour, of Anat., Vol. I, 1901. 
 
 BOLK, L.: Die Segmentaldifferenzierung des menschlichen Rumpfes und seiner Extremi- 
 taten. Morph. Jahrbuch, Bd. XXV, 1898. 
 
 FUTAMURA, R.: Ueber die Entwickelung der Facialismuskulatur des Menschen. 
 Anat. Hefte, XXX, 1906. 
 
 GODLEWSKI, E.: Die Entwickelung des Skelet- und Herzmuskelgewebes der Saugetiere. 
 Arch. }. mik. Anat., Bd. LX, 1902. 
 
 GRAFEXBERG, E.: Die Entwickelung der menschlichen Beckenmuskulatur. Anat. 
 Hefte, 1904. 
 
 HEIDEXHAIX, M.: Structur der contractilen Materie. Ergebnisse der Anat. u. Entivick., 
 Bd. VIII, 1898. 
 
 HEIDEXHAIX, M.: Ueber die Structur des menschlichen Herzmuskels. Anat. Anz., 
 Bd. XX, 1901. 
 
 KASTXER, S.: Ueber die Bildung von animalen Muskelfasern aus dem Urwirbel. 
 Arch. f. Anat. u. Physiol., Anat. Abth., Suppl., 1890. 
 
 KEIBEL, F., and MALL, F. P.: Manual of Human Embryology, Vol. I, 1910. 
 
 KOLLMAXX, J.: Die Rumpfsegmente menschlicher Embryonen von 13-35 Urwirbeln. 
 Arch. f. Anat. u. Physiol., Anat. Abth., 1891. 
 
 LEWIS, W. H.: The Development of the Arm in Man. American Jour, of Anat., Vol. I, 
 1902. 
 
 MAURER, F.: Die Entwickelung des Muskelsystems und der elektrischen Organe. Also 
 Bibliography. In Hertwig's Handbuch der vergl. u. experiment. Entwickelungslehre der 
 Wirbeltiere, Bd. Ill, Teil I, 1904. 
 
 MACCALLUM, J. B.: On the Histology and Histogenesis of the Heart -muscle Cell. 
 Anat. Anz., Bd. XIII, 1897. 
 
 MACCALLUM, J. B.: On the Histogenesis of the Striated Muscle Fiber and the Growth of 
 the Human Sartorius Muscle. Johns Hopkins Hospital Bulletin, Vol. IX, 1898. 
 
 MALL, F. P.: Development of the Ventral Abdominal Walls in Man. Jour, of Mor- 
 phology, Vol. XIV, 1898. 
 
 McGiLL, CAROLIXE: The Histogenesis of Smooth Muscle in the Alimentary Canal and 
 Respiratory Tract of the Pig. Internal. Monatsch. Anat. u. Phys., Bd. XXIV, 1907. 
 
 McMuRRicH, J. P.: The Phylogeny of the Forearm Flexors. American Jour, of Anat., 
 Vol. II, 1903. 
 
 McMuRRicH, J. P.: The Phylogeny of the Palmar Musculature. American Jour, of 
 Anat., Vol. II, 1903. 
 
 MCMURRICH, J. P.: The Phylogeny of the Crural Flexors. American Jour, cf Ana!., 
 
 Vol. rv, 1904. 
 
 MCMURRICH, J. P.: The Phylogeny of the Plantar Musculature. American Jour, of 
 Anat., Vol. VI, 1907. 
 
 POPOWSKY, L: Zur Entwickelungsgeschichte der Dammmuskulatur beim Menschen. 
 Anat. Hefte, 1899. 
 
 SUTTOX, J. B.: Ligaments, Their Nature and Morphology. London, 1897. 
 
 ZIM.MERILA.XX: Ueber die Metamerie des Wirbeltierkopfes. Verhandl. d. Anat. Gesellsch. 
 Jena, 1891. 
 
CHAPTER XII. 
 
 THE DEVELOPMENT OF THE ALIMENTARY TUBE AND 
 APPENDED ORGANS. 
 
 The embryonic disk, composed of the three germ layers, primarily lies flat 
 upon the yolk sac (see p. 135; also Fig. 82). A little later the axial portion of 
 the embryo is indicated by the primitive streak, the neural groove (subsequently 
 the neural tube), the notochord, and the primitive segments (Fig. 74). Then 
 along each side of the axial portion and at the cephalic and caudal ends, the 
 
 Allantoic duct 
 
 Belly stalk 
 
 FIG. 282. Lateral view of human embryo with 14 pairs of primitive segments (2.5 mm.) . Kollmann. 
 
 The yolk sac has been cut off. The fore-gut, mid-gut and hind-gut, as indicated in the figure, 
 
 together constitute the primitive gut. Compare with Fig. 283. 
 
 germ layers bend ventrally and medially and finally meet and fuse in the mid- 
 ventral line (p. 137). The portion of the entoderm ventral to the notochord is 
 bent into a tube which, for the most part, becomes pinched off from the parent 
 entoderm and is suspended in the embryonic coelom by the common mesentery 
 (Figs. 141 and 142). This entodermal tube is the primitive gut. At first it is 
 but slightly elongated and is closed at both ends. On the ventral side, however; 
 
 316 
 
DEVELOPMENT OF THE ALIMENTARY TUBE AND APPENDED ORGANS. 317 
 
 it opens widely into the yolk sac (Figs. 282 and 283). The primitive gut, there- 
 fore, has no communication with the exterior. It communicates at its caudal 
 end with the central canal of the spinal cord through the neurenteric canal (Fig. 84; 
 compare with 85). 
 
 As development proceeds, this simple tube elongates rapidly and becomes 
 differentiated into distinct regions. The cephalic end, in connection with the 
 branchial arches and grooves, becomes the dilated pharyngeal region. Caudal 
 
 Oral fossa 
 Branchial arch I 
 Branchial arch II 
 
 Body wall 
 Coelom 
 
 Fore-gut 
 Mid-gut 
 
 Ccelom 
 Hind-gut 
 
 Belly stalk 
 
 FIG. 283. Ventral view of human embryo of 2.4 mm. His, Kollmann. 
 
 Note the opening in the ventral wall of the gut. This indicates the communication between the 
 gut and the yolk sac. The latter has been removed. Compare with Fig. 282. 
 
 to and continuous with this, is the short, narrow ossophageal region which in 
 turn passes over into the slightly dilated stomach region. The portion of the 
 gut caudal to the stomach is the intestinal region. During the differential 
 changes, the communication with the yolk sac becomes relatively smaller, form- 
 ing the yolk stalk which joins the intestinal portion a short distance caudal to the 
 stomach (Figs. 284 and 285). 
 
 The Mouth. 
 
 At a very early period the primary fore-brain region bends ventrally almost 
 at a right angle to the long axis of the body to form the naso-frontal process. 
 
318 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 As the first branchial arch develops, it grows ventrally until it meets and fuses 
 with its fellow of the opposite side in the midventral line, thus forming the 
 mandibular process. From the cephalic side of the first arch a secondary proc- 
 ess maxillary process develops and fills in the space between the arch itself 
 and the naso-frontal process. These various structures thus bound a distinct 
 depression on the ventral side of the head. This depression is the oral pit, the 
 forerunner of the oral and nasal cavities (Fig. 283; compare with Figs. 282 
 and 122) . The groove in the midventral line between the mandibular processes 
 marks the symphysis of the lower jaws. The groove on each side between the 
 
 Epiglottis 
 
 Tongue 
 Hypophysis 
 
 Larynx 
 
 Lung 
 
 g. L..\ Stomach 
 
 A-- Pancreas 
 
 Urachus 
 
 Mesonephric duct 
 
 Kidney bud 
 
 FIG. 284 Alimentary tube of a human embryo of 4.1 mm. His Kollmann. 
 
 maxillary process and the mandibular process marks the angle of the mouth, 
 The groove between the maxillary process and the naso-frontal process is the 
 naso-optic furrow, at the dorsal end of which the eye develops. 
 
 The bottom of the oral pit is formed by a portion of the ventral body wall, 
 which separates the oral cavity from the cephalic end of the gut, and which is 
 composed of ectoderm and entoderm, with a small amount of mesoderm be- 
 tween. This closing plate, the pharyngeal membrane, which is still present in 
 embryos of 2.15 mm., soon becomes thinner and finally breaks away, leaving 
 the oral pit and the gut in direct communication (Fig. 285). Since the oral pit 
 is lined with ectoderm, the epithelial lining of the mouth or oral cavity is largely of 
 
DEVELOPMENT OF THE ALIMENTARY TUBE AND APPENDED ORGANS. 319 
 
 ectodermal origin. In the medial line of the roof of the ofal cavity, near the 
 pharyngeal membrane, the epithelium (ectoderm) evaginates to form Rathke's 
 pocket. This comes in contact with an evagination from the floor of the brain 
 and with it forms the pituitary body. 
 
 The further development of the mouth consists of an elaboration of the 
 structures which primarily bound the oral pit and the growth of certain new 
 structures such as the teeth and the tongue. The first branchial arch fuses with 
 its fellow of the opposite side in the midventral line to form the symphysis of 
 the lower jaws, giving rise also to the lower lip and chin region. As the naso- 
 frontal process continues to grow, two depressions appear on its ventral border, 
 
 Pharynx 
 
 Hypophysis 
 
 Yolk sac 
 
 Belly stalk 
 Caudal gut 
 
 Branchial arches 
 (pharynx) 
 
 Lung 
 
 Liver 
 
 Stomach 
 
 Pancreas 
 
 Common 
 mesentery 
 
 Mesonephros 
 Allantoic duct 
 
 Hind-gut 
 
 Kidney bud 
 FIG. 285. Sagittal section of reconstruction of a human embryo of 5 mm. His, Kollmann. 
 
 one on each side, a short distance from the medial line. These depressions are 
 the nasal pits which indicate the beginning of the external openings of the nasal 
 passages. The part between the nasal pits is destined to give rise to the nasal 
 septum and the medial part of the upper lip (Fig. 136). The primary oral 
 cavity is divided into the oral cavity proper and the nasal cavity by outgrowths 
 from the maxillary processes. From the medial side of each maxillary process 
 a plate-like structure grows across the primary oral cavity toward the medial 
 line (Fig. 178). These two plates, or palatine processes, meet and fuse with the 
 lower part of the nasal septum (Fig. 286) . (For further details of this fusion, see 
 page 148 and page 195). The palatine processes thus form the palate, or the 
 roof of the mouth, which separates the mouth cavity from the nasal cavity. The 
 palate does not extend far enough backward, however, to separate the posterior 
 
320 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 part of the nasal cavity from the pharynx. Thus the posterior nares and 
 pharynx are left in communication. Externally the maxillary processes extend 
 medially, separate the nasal pits from the oral cavity, and form the lateral 
 portions of the upper lip (Fig. 137). 
 
 Jacobson's organ 
 Inferior concha 
 
 Jacobson's cartilage 
 
 Palatine process 
 
 Nasal septum 
 
 Nasal cavity 
 
 Oral cavity 
 
 FIG. 286. From a section through the head of a human embryo of 28 mm., showing the nasal 
 septum, the nasal cavities, the oral cavity, and the palatine processes. Peter. 
 
 The Tongue. The tongue develops from three separate anlagen which 
 unite secondarily. In embryos of about 3 mm. a slight elevation appears on the 
 floor of the pharynx in the region of the first branchial arch. This is the 
 
 Tuberculum impar 
 
 Root of tongue 
 
 Inner branchial 
 groove IV 
 
 Crista terminalis 
 
 Lung 
 FIG. 287. Floor of the pharyngeal region of a human embryo of about 3 weeks. His. 
 
 tuberculum impar, being, as the name indicates, unpaired, and is destined to give 
 rise to the tip and body of the tongue (Fig. 287) . Soon afterward two bilaterally 
 symmetrical elevations appear on the floor of the pharynx, which are destined to 
 give rise to the root of the tongue (Fig. 288). These paired elevations, arising 
 
DEVELOPMENT OF THE ALIMENTARY TUBE AND APPENDED ORGANS. 321 
 
 in the region of the second and third branchial arches, gradually enlarge and 
 unite with each other and with the tuberculum impar, leaving between the 
 latter and themselves, however, a V-shaped groove (Fig. 289). At the apex of 
 the groove there is a depression the foramen ccecum lingua which is the ex- 
 ternal opening of the thyreoglossal duct (see p. 332). The groove later disap- 
 pears, but its position is indicated in the adult by the vallate papillae. 
 
 According to Hammar, the tuberculum impar is a transitory structure and does not 
 give rise to the tip and body of the tongue. The tip and body are derived from a much 
 more extensive elevation in the floor of the pharynx. 
 
 The tongue as a whole enlarges and grows from its place of origin toward 
 the entrance to the primary oral cavity. For a time it practically fills the cavity. 
 When the palate develops it recedes and finally comes to lie on the floor of the 
 oral cavity proper, as in the adult. The growth of the tongue involves the 
 
 Tuberculum impar 
 
 Root of tongue 
 Epiglottis 
 
 FIG. 288. Floor of pharyngeal region of a human embryo of 12.5 mm. His. 
 
 epithelial lining of the pharynx and oral cavity and also the underlying mesen- 
 chymal tissue. The latter produces the connective tissue and at least a part of 
 the intrinsic muscle fibers of the tongue. The papillae involve the epithelium 
 and connective tissue, while the glands and taste buds are derived from the 
 epithelium alone. 
 
 The portion of the lingualis muscle innervated by the facial (VII) nerve is probably 
 derived from the mesenchymal tissue in the tongue anlage. The rest of the muscle is 
 innervated by fibers from the hypoglossal (XII) nerve, indicating a possible derivation from 
 certain rudimentary segments in the occipital region which correspond to the three roots of 
 the nerve. This would make it appear that during phylogenesis a part of the lingualis 
 muscle has grown into the tongue from a region caudal to the last branchial arch 
 
 The lingual papilla begin to develop during the third month. Their 
 development is limited to the dorsum of the tongue and to the portion derived 
 from the tuberculum impar. In other regions slight elevations may appear, but 
 not in the form of distinct papillae. The jungijorm and filijorm papillae appear 
 as pointed elevations in the connective tissue, which push their way into the 
 epithelium, the latter at the same time being raised above the surface over these 
 
322 TEXT-BOOK OF EMBRYOLOGY. 
 
 points. Gradually the little masses of connective tissue assume the shapes 
 characteristic of fungiform or filiform papillae. During the fifth month 
 the epithelium between the papillae apparently degenerates to some extent, 
 thus leaving them projecting still farther above the surface. The forma- 
 tion of papillae probably goes on for some time after birth, since at birth their 
 form, size, number and arrangement are not the same as at later periods. It is 
 an interesting fact that the filiform papillae lose many of their taste buds after 
 the child is weaned. 
 
 The anlage of the vallate papillae appears as a ridge along the V-shaped line 
 of fusion between the paired and unpaired portions of the tongue. The ridge is 
 apparently formed by the ingrowth of a solid mass of epithelium along each 
 side, although the connective tissue between the masses may grow toward the 
 surface to some extent. Later the ridge is broken up into the individual papillae 
 
 Tuberculum impar 
 
 Root of tongue 
 
 Epiglottis 
 ' Larynx 
 FIG. 289. Dorsal view of the tongue of a human embryo of 20 mm. His, Bonnet. 
 
 by the ingrowth of the epithelium at certain points. The more superficial cells 
 of the masses then degenerate, thus leaving each papilla surrounded by a trench 
 and wall. 
 
 The development of the lingual glands is confined for the most part to the 
 root and inferior surface and to the region of the vallate papillae. The glands 
 begin to develop during the fourth month as solid ingrowths of epithelium, the 
 mucous glands appearing first, the serous somewhat later. The epithelial 
 masses acquire lumina and grow deeper into the tongue, where they usually 
 branch and coil to form the secreting portions. The latter open to the surface 
 through the original ingrowths which become the ducts. Ebner's glands 
 develop from the bottoms of the trenches around the vallate papillae. 
 
 The Teeth. The development of the teeth involves the ectoderm and 
 mesoderm, the former giving rise to the enamel, the latter to the dentine and 
 pulp. In human embryos of 12-15 mm - (thirty-four to forty days), before 
 the lip groove is formed, a thickening of the epithelium (ectoderm) takes place 
 
DEVELOPMENT OF THE ALIMENTARY TUBE AND APPENDED ORGANS. 323 
 
 along the edges of the processes that bound the slit-like entrance to the mouth. 
 When the lip groove appears (Fig. 178), the epithelial thickening comes to lie 
 along the edge of the jaw, or in other words, along the edge of the gums. It 
 then grows into the mesenchymal tissue (mesoderm) of the jaw obliquely toward 
 the lingual surface to form the dental shelf. A little later the dental groove 
 appears on the edge of the jaw, along the line where the ingrowth of epithelium 
 took place. 
 
 Epithelium of mouth cavity 
 
 Inner 
 enamel cells 
 
 Dental papilla -J-H 
 
 Neck of 
 enamel organ 
 
 Germ of 
 permanent tooth 
 
 M Bone of 
 lower jaw 
 
 FIG. 290. Section of developing tooth from a 3^ months human foetus. Szymonowicz. 
 
 Note the portion of the original dental shelf connecting the developing tooth with the 
 
 epithelium of the mouth cavity. 
 
 The dental shelf is at first of uniform thickness, but in a short time five 
 enlargements appear in it in each upper and lower jaw, indicating the begin- 
 nings of the milk teeth. When the embryo reaches a length of 40 mm. (an age of 
 eleven to twelve weeks) the mesenchymal tissue on one side of these enlargements 
 (above and to the inner side in the upper jaw, below and to the inner side in the 
 lower jaw) becomes condensed and pushes its way into the epithelium. Each of 
 these mesenchymal ingrowths is a dental papilla. Thus at this stage the anlage 
 of each tooth is a mass of epithelium fitting cap-like over a mesenchymal papilla. 
 The epithelium is the forerunner of the enamel organ; the papilla is destined to 
 give rise to the dentine and pulp. The anlagen are connected with one another 
 
324 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 by intermediate portions of the dental shelf, and with the surface by the 
 original ingrowth of epithelium. 
 
 THE ENAMEL. The epithelial cells nearest the dental papilla become high 
 columnar in shape, forming a single layer. Those in the interior of the mass 
 become separated and changed into irregular, stellate, anastomosing cells, with 
 a fluid intercellular substance, constituting the enamel pulp. Those farthest 
 from the papilla become flattened (Fig. 290; compare with Fig. 291). Calcifi- 
 cation begins in the basal ends of the columnar cells, or in the ends next the 
 
 Enamel 
 Dentine j Enamel prisms 
 
 Odontoblasts 
 
 r. 
 
 *-a~ --rr- Outer } 
 
 I enamel 
 _ cells 
 
 - Inner J 
 
 Enamel pulp 
 
 FIG. 291. Section through the border of a developing tooth of a new-born puppy. "Bonnet. 
 
 papilla, and in the intercellular substance, and gradually progresses throughout 
 the cells, the latter at the same time becoming much more elongated. Thus the 
 cells are transformed into enamel prisms which are held together by the calci- 
 fied intercellular substance (Fig. 291). 
 
 The formation of enamel begins in the milk teeth toward the end of the 
 fourth month and probably continues until the teeth break through the gums. 
 The enamel organ at first surrounds the entire developing tooth except where 
 the papilla joins the underlying mesenchymal tissue (Fig. 290). Later the 
 deeper part of the organ disappears as such, and the enamel is formed only on 
 that part of the tooth which eventually becomes the crown. The enamel pulp 
 increases in amount for a time, but subsequently disappears as the tooth grows 
 into it (Fig. 292). Its function is not fully understood. It may serve as a line 
 
DEVELOPMENT OF THE ALIMENTARY TUBE AND APPENDED ORGANS. 325 
 
 of least resistance in which the tooth grows, and it may convey nourishment 
 to the enamel cells, the enamel organ being non-vascular. 
 
 The Dentine and Pulp. At first the dental papilla is simply a condensation 
 of mesenchyme, but later it is converted into a sort of connective tissue pene- 
 trated by blood vessels and nerves (Fig. 292). The cells nearest the enamel 
 organ become columnar and arranged in a single layer, with the nuclei 
 toward their inner ends. The outer ends are blunt, while the inner ends are 
 
 Epith. of mouth cavity 
 
 Outer) 
 
 > enamel cells 
 
 Dental sac 
 
 Bone of jaw 
 
 Blood vessel 
 
 Enamel pulp 
 (remnant) 
 
 Papilla 
 FIG. 292. Longitudinal section of a developing tooth of a new-born puppy. Bonnet. 
 
 continued as slender processes that extend into the pulp and probably fuse 
 with other cell processes. These columnar cells are the odontoblasts, under the 
 influence of which the lime salts of the dentine are deposited, and which are com- 
 parable with the osteoblasts in developing bone. 
 
 Toward the end of the fourth month the odontoblasts form a membrane- 
 like structure, the membrana preformativa, between themselves and the enamel. 
 This membrane is first converted into dentine by the deposition of lime salts, 
 after which the process of calcification progresses from the enamel toward the 
 
326 TEXT-BOOK OF EMBRYOLOGY. 
 
 pulp. During calcification slender processes of the odontoblasts remain in minute 
 channels, or dentinal canals, forming the dentinal fibers which anastomose with 
 one another (Fig. 291). In the peripheral part of the dentine certain areas 
 apparently fail to become calcified and form the inter globular spaces. The same 
 cells that are originally differentiated from the mesenchyme probably persist 
 throughout development as the odontoblasts and produce the entire amount of 
 dentine in a tooth. Even in the fully formed tooth there is a layer of odonto- 
 blasts bearing the same relation to the dentine and pulp as in the developing 
 tooth. The chief difference between dentine formation and bone formation is 
 that in the latter the osteoblasts become enclosed to form bone cells, while in 
 the former the odontoblasts merely leave processes enclosed as the cell bodies 
 recede. 
 
 The pulp of the tooth is of course derived from the mesenchymal tissue in 
 the interior of the dental papilla (compare Figs. 290 and 292). The blood 
 vessels and nerves grow in from the underlying connective (mesenchymal) tissue. 
 
 At an early stage the mesenchymal tissue around the anlage of the tooth, in- 
 cluding the enamel organ, condenses to form a sort of sheath, the dental sac, 
 which is later ruptured when the tooth breaks through the gum (Fig. 292). 
 The cement is formed around the root of the tooth from the tissue of the dental 
 sac in the same manner as subperiosteal bone is formed from osteogenetic tissue 
 (p. 174). In fact, cement is true bone without Haversian systems. 
 
 The milk teeth, which are the first to develop and the first to appear above 
 the surface, are represented by the medial incisors, lateral incisors, canines, and 
 molars, to the number of ten in the upper and ten in the lower jaw. They may 
 be indicated graphically thus: 
 
 M. 
 
 C. 
 
 L.I. 
 
 M.I. 
 
 M.I. 
 
 L.I. 
 
 C. 
 
 M. 
 
 2 
 
 i 
 
 i 
 
 i 
 
 i 
 
 i 
 
 i 
 
 2 
 
 2 
 
 i 
 
 i 
 
 i 
 
 i 
 
 i 
 
 i 
 
 2 
 
 M. 
 
 C. 
 
 L.I. 
 
 M.I. 
 
 M.I. 
 
 L.I. 
 
 C. 
 
 M. 
 
 -^-=20 
 IO 
 
 In describing the formation of the dental shelf, it was noted that the papilke 
 of the milk teeth grow into corresponding thickenings of the epithelium (p. 323). 
 The growth takes place from the side, thus leaving the edge of the shelf free to 
 grow farther toward the lingual side of the jaw. In this free edge other tooth 
 germs arise, which mark the beginnings of the permanent teeth (Fig. 290). In 
 addition to the germs that correspond in position to the milk teeth, three others 
 arise in each jaw, representing the true molars of the adult. The latter arise in a 
 part of the dental shelf which has grown toward the articulation of the jaws 
 without coming in contact with the surface epithelium. The first papilla of 
 the permanent dentition to appear is that of the first molar. It appears im- 
 mediately behind the second milk molar at a time when the milk teeth are well 
 
DEVELOPMENT OF THE ALIMENTARY TUBE AND APPENDED ORGANS. 327 
 
 advanced (embryos of 180 mm., about seventeen weeks). The permanent 
 incisors and canines appear about the twenty-fourth week; the premolars, which 
 correspond to the milk molars, about the twenty-ninth week. The second 
 molar does not appear till after birth (six months), and the third molar, or 
 wisdom tooth, begins to develop about the fifth year. 
 
 The formation of the anlagen of the permanent teeth and the development of 
 the enamel, dentine and pulp take place in precisely the same manner as in the 
 milk teeth. The true molars grow out through the gums in the same way as 
 the milk teeth. Those permanent teeth which correspond in position to milk 
 teeth grow under the latter, exert pressure on their roots and thus loosen and 
 finally replace them. The two sets of teeth may be graphically represented 
 thus: 
 
 16 
 
 Normally all the epithelium of the dental shelf, except the parts directly con- 
 cerned in the development of the teeth, disappears at times which vary in differ- 
 ent individuals. Occasionally, however, remnants of this epithelium give rise 
 to cystic structures (developmental tooth tumors). 
 
 :^' : -_- Tongue 
 P. 
 
 Upper 
 Upper 
 
 Jaw Permanent, 
 
 Taw Milk, 
 
 M. 
 
 Pm. 
 
 II 
 M 
 
 C. 
 
 II 
 
 c 
 
 L.I. 
 
 II 
 L T 
 
 M.I. 
 
 A 
 
 M.I. 
 
 M"T 
 
 L.I. 
 
 T"T 
 
 c. 
 
 II 
 c 
 
 Pm. 
 
 ,!! 
 
 M. 
 
 1! 
 
 
 
 3 
 
 2 
 
 I 
 
 
 
 
 
 
 2 
 
 1 
 
 Lower 
 Lower 
 
 Jaw Milk, 
 Taw Permanent, 
 
 3 
 M. 
 
 2 
 
 M. 
 
 I 
 
 I 
 
 c. 
 
 ! 
 
 i 
 L.I. 
 
 T!'T 
 
 I 
 M.I. 
 
 Jl 
 
 M.I. 
 
 J'i 
 
 I 
 
 L.I. 
 
 A 
 
 I 
 
 c. 
 
 II 
 
 c. 
 
 2 
 M. 
 
 Pi 
 
 3 
 
 I 
 
 Subling. gland 
 
 Submax. gland 
 
 Palatine process 
 
 Submax. gland 
 
 Lingual nerve 
 FIG. 293. From a transverse section through the tongue and oral cavity of a mouse embryo. Goppert, 
 
 The Salivary Glands. The anlage of the submaxillary gland appears, in 
 embryos of 10 to 12 mm., as a flange of epithelium directed ventrally from 
 the portion of the lingual sulcus just caudal to the crossing of the lingual 
 nerve. The flange grows into the mesenchyme of the lower jaw, and at an 
 early period becomes triangular with its longest side free and a free vertical 
 caudal border. Cell proliferation begins at the angle of union of the two 
 borders and gradually progresses cephalad along the longest border, thus 
 producing a solid ridge-like thickening of the latter. 
 
328 TEXT-BOOK OF EMBRYOLOGY. 
 
 The main portion of the gland is produced by a sprouting of the epithelium 
 from the angle of union of the two free borders of the flange and grows deep 
 into the mesenchyme along the mesial side of the ramus of the mandible. 
 The sprouts branch repeatedly in the course of their development, thus laying 
 the foundation for the division of the gland into lobes and lobules. 
 
 The distal end of the duct of the submaxillary (Wharton's) is formed from 
 the ridge-like thickening of the free margin of the flange through a dissolu- 
 tion of the greater part of the flange between the lingual sulcus and the 
 thickened margin itself, thus freeing this portion of the duct from the sulcus. 
 By a continuation of the growth which produced the ridge along the free 
 border of the original flange an extension of this same ridge is produced along 
 the bottom of the lingual sulcus forward toward the chin region. This portion 
 of the ridge is progressively constricted off from the sulcus from behind 
 forward, until finally the attachment of the duct reaches its definitive position 
 at the side of the frenulum linguae. 
 
 The anlage of the Bartolinian element of the sublingual gland appears as 
 a smaller flange attached to the lateral border of the submaxillary flange near 
 the crossing of the lingual nerve and prolonged forward by an interrupted 
 crest along the lingual sulcus. Its later development is similar to that of the 
 submaxillary. 
 
 A small medial flange also on the submaxillary flange gives rise to a sprout 
 in much the same manner as the other anlagen. While the history of this 
 anlage is not complete in the human embryo, it probably gives rise to the 
 anterior lingual gland (gland of Blandin and Nuhn). The alveolingual ele- 
 ments arise from a keel attached to the alveolingual sulcus (the groove 
 between the floor of the mouth and the alveolar process of the lower jaw). 
 
 The parotid gland originates from the buccal sulcus in essentially the same 
 way as the submaxillary arises from the lingual sulcus. The anlage then 
 continues to grow through the mesenchyme of the cheek across the masseter 
 muscle, the distal end branching freely to form the secreting portion of the 
 gland. The outgrowths are at first solid, but later become hollow, the 
 proximal portion of the original outgrowth forming the parotid (Steno's) 
 duct, the more distal portions forming the smaller ducts and terminal tubules. 
 
 The histogenetic changes in the salivary glands probably continue until the 
 child takes solid food, when the glands become of greater functional importance. 
 In the parotid gland, which is serous in man, the original, undifferentiated 
 epithelial cells undergo changes in form and arrangement so that by the 
 twenty-second week the larger ducts are lined with a two-layered epithelium, 
 the smaller ducts with a simple cuboidal epithelium, and the terminal tubules with 
 a single layer of high columnar cells. The two-layered epithelium in the larger 
 ducts persists. The ducts lined with the cuboidal epithelium become the 
 
DEVELOPMENT OF THE ALIMENTARY TUBE AND APPENDED ORGANS. 329 
 
 socalled intermediate tubules, the cells changing to a flat type. The high 
 columnar cells of the terminal tubules become the serous secreting cells. 
 
 Quite similar changes also occur in the submaxillary, but in foetuses of 
 eight to nine months the crescents of Gianuzzi appear as masses of darkly 
 staining cells forming the ends or sides of the terminal tubules. The crescents 
 at first border on the lumina, but later, probably by a process of evagination, 
 come to lie on the surface of the tubules. 
 
 The beginning of the secretory function may be detected by a diminution in 
 the affinity of the cells for stains. 
 
 The Pharynx. 
 
 The pharynx develops from the cephalic end of the primitive gut. This 
 part of the gut is primarily of uniform diameter, is broadly attached by meso- 
 derm to the dorsal body wall, and ends blindly (Fig. 285). When the branchial 
 arches and grooves develoo in this (the cervical) region, they affect the gut as 
 
 Neural tube 
 (brain) 
 
 Maxillary process 
 Mandibular process 
 
 Heart -- . 
 
 , Notochord 
 
 . Branchial arches and 
 grooves (pharynx) 
 
 ;-- Lung groove 
 
 FIG. 294. Sagittal section through the head of a human embryo of 4.2 mm. (31-34 days). His. 
 
 well as the periphery of the body. The arches form ridges on the surface of the 
 body (Fig. 122) and at the same time form ridges on the wall of the gut. The 
 grooves form pockets which alternate with the arches (Fig. 294). The pockets 
 in the pharyngeal cavity, or inner branchial grooves, are directed outward 
 toward corresponding outer branchial grooves (Fig. 287). The arches are 
 covered externally with ectoderm, internally with entoderm, and are filled with 
 mesoderm. Between the arches, or in the grooves, the ectoderm and entoderm 
 are in contact or nearly so. Thus the pharynx is not surrounded by a ccelomic 
 cavity. 
 
330 TEXT-BOOK OF EMBRYOLOGY. 
 
 Since the branchial arches develop in such a way that they are successively 
 smaller from the first to the fourth, the pharyngeal cavity becomes funnel- 
 shaped (Fig. 294). It also becomes somewhat flattened in the dorso- ventral 
 direction, and in the earlier stages when the arches and grooves are fully formed, 
 the pharynx constitutes approximately one- third the entire gut (Fig. 285). 
 Primarily the pharyngeal cavity is separated from the oral cavity by the pharyn- 
 geal membrane (see p. 318; also Fig. 282). When this ruptures and disappears 
 (during the fourth week ?) the two cavities are in open communication. What 
 point in the adult represents the attachment of the pharyngeal membrane is 
 not known; but the glosso- and pharyngopalatine arches (pillars of the fauces) 
 are usually- considered as the boundary between the mouth and pharynx. The 
 caudal limit of the pharynx is the opening of the larynx (Figs. 285 and 294). 
 
 Thus in the early stages the general adult character of the pharynx is es- 
 tablished. While the branchial arches and grooves undergo profound changes, 
 the pharyngeal cavity retains the same relation to the mouth and to the oeso- 
 phagus and respiratory tract. The cavity becomes relatively shorter, however, 
 and the alternating ridges and pockets in its walls are lost as the arches and 
 grooves are transformed into other structures. The metamorphosis of the 
 arches and grooves is considered elsewhere (p. 145). 
 
 THE TONSILS. The tonsils arise in the region of the ventral part of the 
 second inner branchial groove. During the third month the epithelium 
 (entoderm) grows into the underlying connective (mesenchymal) tissue in the 
 form of a hollow bud. From this, secondary buds develop, which are at first 
 solid, but later (during the fourth or fifth month) become hollow by a disappear- 
 ance of the central cells and open into the cavity of the primary bud, thus form- 
 ing the crypts. Lymphoid cells wander from the neighboring blood vessels, or 
 are derived directly from the epithelium (Retterer), and with the connective 
 tissue form a diffuse lymphatic tissue under the epithelium (Fig. 295). By the 
 eighth month the cells become more numerous in places, and by the third 
 month after birth form distinct lymph follicles with germinal centers. The 
 formation of follicles goes on slowly and is probably not complete until 
 some time after birth. 
 
 The Lingual Tonsils. The lymphatic tissue of the tongue develops in rela- 
 tion to the lingual glands. During the eighth month lymphoid infiltration 
 occurs around the ducts of the glands, and the connective tissue acquires the 
 reticular character. True follicles probably do not appear until the child is at 
 least five years old. 
 
 The Pharyngeal Tonsils. During the sixth month small folds appear in the 
 mucous membrane of the roof of the pharynx and become diffusely infiltrated 
 with lymphoid cells. This occurs first in the posterior part of the roof, but later 
 (seventh or eighth month) it extends forward and along the sides of the naso- 
 
DEVELOPMENT OF THE ALIMENTARY TUBE AND APPENDED ORGANS. 331 
 
 pharygeal cavity. By the end of foetal life the ridges become quite large. 
 Follicles may appear before birth or not until one or two years later. After 
 puberty the ridges almost completely disappear, but the adenoid tissue remains 
 wholly or in part. 
 
 The bursa pharyngea is an evagination from the roof of the pharynx about 
 the upper border of the superior constrictor muscle, and is apparent in em- 
 bryos of eleven weeks. It probably has no genetic relation to the hypophysis. 
 Its significance is not known. 
 
 FIG. 295. Section through the middle of the developing tonsil of a human 
 
 embryo of 5 months. Stohr. 
 
 6, Epithelial buds (secondary outgrowths) from the epithelium lining the primary crypt (c); 
 L, lymphoid infiltration of the connective (mesodermal) tissue. 
 
 THE BRANCHIAL EPITHELIAL BODIES. 
 
 THE THYREOID- GLAND. The thyreoid arises, after the manner of ordinary 
 glands, as an evagination from the epithelium of the pharynx. It appears in 
 embryos of 3 to 5 mm. as a ventral outgrowth of epithelium in the floor of the 
 pharynx, at the point where the tuberculum impar and the tw r o paired anlagen 
 of the tongue join (Fig. 296). This point is the foramen caecum linguae which 
 has already been mentioned in connection with the development of the tongue 
 (p. 32 1) . The evagination grows into the mesodermal tissue in the ventral wall 
 of the neck, and forms a transverse mass of epithelium. The latter breaks up 
 into irregular cords of cells which, by a further process of budding, grow cau- 
 dally along the ventral surface of the larynx. The cords of cells are from the 
 first surrounded by connective tissue and later also become surrounded by net- 
 works of capillaries (Fig. 297). They ultimately break up into smaller masses 
 which become hollow and form the alveoli. Colloid secretion begins toward 
 the end of fcetal life or soon after birth. 
 
 As the gland grows toward its final position it becomes enlarged laterally into 
 the two lateral lobes, which remain connected by the isthmus (Fig. 298). The 
 pyramidal process represents either a secondary outgrowth from the isthmus or 
 one of the lobes, or a remnant of the original connection with the tongue, that is, 
 
332 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 of the thyreo glossal duct. The duct usually disappears for the most part, but 
 certain structures sometimes found in the adult in the line of the duct are 
 possibly remnants of it. They have been variously named, according to their 
 position, accessory thyreoid y suprahyoid, and prehyoid glands (Fig. 298). 
 
 A pair of structures, appearing first in embryos of 8 to 10 mm., arise as 
 evaginations from the ventral ends of the fourth inner branchial grooves. They 
 grow into the mesodermal tissue and then caudally along the ventro-lateral side 
 
 Notochord 
 
 Thymus 
 
 Thyreoid 
 
 Jugular vein 
 Vagus nerve 
 
 Carotid artery 
 Parathyreoid (epith. body) 
 
 Thymus (in. br. groove III) 
 
 Heart 
 
 FIG. 296. Transverse section through the region of the 3d branchial .groove 
 
 of an Echidna embryo. Maurer. 
 i.= Pharynx, below which are the paired anlagen of the tongue. 
 
 of the larynx, where they come into close relation with the lateral lobes of the 
 thyreoid (Fig. 298). They have been called the lateral thyreoids, and acquire 
 the thyreoid structure. 
 
 Considerable confusion has arisen in regard to the lateral thyreoids. The earlier investi- 
 gators held that they were derived from the fourth groove and united with the medial portion, 
 which appeared at the foramen caecum, to become integral parts of the thyreoid. Further 
 researches among the lower Vertebrates led others to deny that the thyreoid arose other 
 than as a medial anlage, and that the so-called lateral thyreoids in the embryo were the 
 postbranchial bodies which never assumed the thyreoid structure, but atrophied and dis- 
 appeared. More recently it has been thought that, although the postbranchial bodies do 
 not function in the lower Vertebrates, they may in the higher Mammals and man unite with 
 the medial thyreoid and secrete colloid. 
 
 The parathyreoids or epithelial bodies also come into close relation with the 
 thyreoid. They arise as paired evaginations from the cephalic sides of the third 
 
DEVELOPMENT OF THE ALIMENTARY TUBE AND APPENDED ORGANS. 333 
 
 and fourth grooves, dorsal to the thymus and the lateral thyreoid evaginations 
 (Figs. 296 and 299). As the thyreoid grows caudally from its point of origin, 
 these bodies come to lie close to it or may even become embedded in it (Fig. 298). 
 They acquire a structure which resembles that of the suprarenal gland and not 
 
 Trachea 
 
 Lateral lobe 
 
 Capillaries 
 Isthmus 
 
 FIG. 297. Section of the right half of the thyreoid gland of a pig embryo of 22.5 mm. Born. 
 
 Accessory thyroeids 
 
 Accessory tnyroeids 
 (thyreoglossal duct; 
 
 I 
 
 Carotid artery 
 
 P.-th. 
 
 Lat. thyreoid 
 (postbr. body) 
 
 Rignt subclavian artery 
 
 Thymus 
 
 Pyramidal process 
 
 Carotid artery 
 Lateral thyreoid 
 Isthmus 
 
 Lumen in thymus 
 subclavian artery 
 
 Arch of aorta 
 
 FlG. 298. Branchial groove derivatives of a rabbit embryo of 16 mm. P.-th., parathyreoid 
 or epithelial body. Verdun, Bonnet. 
 
 that of the thyreoid. Their relation to the latter organ seems to be purely 
 topographical. 
 
 THE THYMUS. The thymus appears in embryos of about 6 mm. as an 
 entodermal evagination from the ventral part of the third branchial groove on 
 
334 TEXT-BOOK OF EMBRYOLOGY. 
 
 each side (Fig. 296) . The outgrowths are at first hollow and communicate with 
 the pharyngeal cavity; later they become solid and (in embryos of 14 mm.) lose 
 their connection with the parent epithelium. They elongate and grow caudally 
 in the mesodermal tissue until (in embryos of 16 mm.) their caudal ends lie 
 ventral to the carotid arteries (Fig. 298). In embryos of 29 mm. their caudal 
 ends rest upon the cephalic surface of the pericardium, their cephalic ends 
 reaching to the isthmus of the thyreoid. The two parts eventually fuse to a 
 considerable extent, but the gland as a whole always consists of two distinct 
 lobes. 
 
 The gland continues to enlarge, at the same time becoming lobulated by the 
 ingrowth of connective tissue, until the child is two or three years old. At this 
 time it is situated in the anterior mediastinum, usually in the medial line. After 
 this it begins to atrophy and becomes a mass of fibrous and fatty tissue through 
 the growth of the interlobular septa and their encroachment upon the lobules. 
 The classical view that the thymus begins to atrophy after the second or third 
 year and is quite degenerated in the adult has recently been somewhat offset 
 
 Lat. thyreoid 
 (postbr. body) 
 
 FIG. 299. Diagram of the branchial groove derivatives in man. Verdun. 
 
 by the view that comparatively slight changes take place in it until puberty. 
 According to the latter view, degeneration goes on after puberty at a rate which 
 varies widely in different individuals, and the thymus may persist as a functional 
 organ up to the age of sixty years. 
 
 The histogenesis of the thymus has been a subject of much study and con- 
 troversy, not only in regard to its origin, but also in regard to its change from 
 an epithelial to a lymphoid structure and the regressive changes in the latter. 
 It has almost certainly been proven to be of entodermal origin. It is at first an 
 epithelial mass which later becomes broken up into lobules by the ingrowth of 
 connective tissue. In regard to the histological changes which it undergoes, 
 the older views are in general that a " pseudomorphosis " takes place; that is, 
 the epithelial elements are replaced by lymphoid cells which wander in from 
 the neighboring blood vessels, HassalPs corpuscles being remnants of the 
 epithelium. Later other investigators looked upon the changes as a " transfer- 
 
DEVELOPMENT OF THE ALIMENTARY TUBE AND APPENDED ORGANS. 335 
 
 mation," asserting that the epithelial cells were transformed into lymphoid 
 cells in situ, and that Hassall's corpuscles were remnants of epithelium and 
 disintegrating blood vessels. Some went even so far as to assert that 
 
 the thymus was the first place of origin of 
 the leucocytes. More recent researches 
 furnish very strong evidence that no lymph- 
 oid cells are derived from the epithelial 
 cells (Maximow), but that the epithelium is 
 transformed into the reticular tissue of the 
 thymus, in which the lymphoid cells undergo 
 mitotic division, Hassall's corpuscles possibly 
 representing compressed parts of the reticu- 
 lum (Hammar) (Fig. 300). 
 
 THE GLOMUS CAROTICUM. The early 
 formation of the glomus caroticum (carotid 
 FIG. 300. Hassall's corpuscle from gland) has not been observed in the human 
 ^mnr^lr. 1 " 11311 ^'" 50 ' embryo. From observations on lower 
 
 animals it has not been made clear whether 
 
 it is derived from the entoderm of a branchial groove or from the adventitia 
 of the carotid artery. 
 
 The (Esophagus and Stomach. 
 
 THE (ESOPHAGUS. When the primitive gut becomes differentiated into 
 distinct regions (p. 317), the cesophageal region forms a comparatively short 
 tube, of uniform diameter, extending from the pharynx to the stomach (Fig. 
 285). In embryos of about 3 to 4 mm. the anlage of the respiratory system 
 arises from the cephalic end of the tube (see p. 360). The latter is lined with 
 entoderm and broadly attached to the dorsal body wall by mesoderm (Fig. 285). 
 During later stages it becomes relatively longer as the heart recedes into the 
 thorax (p. 245), but maintains its uniform diameter. 
 
 Further development produces no marked changes in the relative position 
 of the oesophagus. It remains broadly attached to the dorsal body wall 
 throughout the life of the individual. In other words, there is never a distinct 
 mesentery. The entoderm gives rise to the epithelial lining and the glands, the 
 surrounding mesoderm to the connective tissue and muscular coats. 
 
 THE STOMACH. The anlage of the stomach can br recognized in embryos 
 of about 5 mm. as a slight spindle-shaped enlargement of the primitive gut a 
 short distance cranial to the yolk stalk (Fig. 284). The dilatation goes on more 
 rapidly on the dorsal than on the ventral side, thus producing the greater and 
 lesser curvature respectively. The greater curvature is attached to the dorsal 
 body wall by the dorsal mesogastrium which is a part of the common mesentery. 
 
336 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 The lesser curvature is connected with the ventral body wall by the ventral 
 mesogastrium (Fig. 301). 
 
 In further development, apart from histogenesis, the greater curvature 
 becomes much more prominent and the organ as a whole changes its position, 
 the latter process beginning in embryos of 12 to 14 mm. The cephalic (car- 
 diac) end moves toward the left side of the body, the pyloric end toward the 
 right At the same time the stomach rotates, the greater curvature turning 
 
 Ventral mesogastrium 
 
 -Aorta 
 
 Spleen 
 "" Dorsal mesogastrium 
 
 Coeliac artery 
 
 Pancreas 
 
 Sup. mesenteric artery 
 
 r Common mesentery 
 
 Inf. mesenteric artery 
 
 Hind-gut (rectum) 
 FIG. 301. Gastrointestinal tract and mesenteries of a human embryo of 6 weeks. Toldt. 
 
 Caecum 
 
 caudally from its dorsal position and the lesser curvature cranially from its 
 ventral position. The result is that the organ comes to lie in an approximately 
 transverse position in the body, with the cardiac end to the left, the pyloric end 
 to the right, the greater curvature directed caudally, and the lesser curvature 
 directed cranially (compare Figs. 285 and 301 with Figs. 314 and 342).* 
 
 * These changes may be more easily understood if the student will hold a closed book in the 
 sagittal plane in front of him, with the back of the book toward, and the open edge away from him. 
 The back represents the greater curvature, the open edge the lesser curvature. The upper end of 
 the book represents the cardiac end of the stomach, the lower end the pylorus. Turn the upper 
 (cardiac) end to the left, the lower (pyloric) end to the right, at the same time allowing the back of 
 the book (the greater curvature) to drop downward on the side toward the body. The changes in 
 the position of the book represent the changes in the position of the developing stomach. 
 
DEVELOPMENT OF THE ALIMENTARY TUBE AND APPENDED ORGANS. 337 
 
 It is obvious that the lower end of the oesophagus is carried toward the left 
 side of the body with the cardiac end of the stomach, and at the same time 
 twisted so that the side which originally faced the left comes to face ventrally. 
 The changes in the mesentery which accompany the changes in the stomach 
 are described elsewhere (p. 378). 
 
 The torsion of the stomach also produces an asymmetrical condition of the 
 vagi nerves. The latter reach the stomach before it changes its position. As 
 the changes take place, the left nerve is carried around to the left and ventrally 
 so that in the adult it passes through the diaphragm ventral to the oesophagus 
 and extends over the ventral surface of the stomach. The right nerve passes 
 over the dorsal surface of the stomach. 
 
 The Intestine. 
 
 When the primitive gut is differentiated into recognizable regions (p. 317) 
 the intestinal region forms a simple tube, of uniform diameter, extending from 
 the stomach to the caudal end of the embryo where it ends blindly. The yolk 
 stalk is attached to the intestine a short distance from the stomach. Near the 
 caudal end the allantoic duct arises (p. 114). The lumen of the yolk stalk and 
 of the allantoic duct is continuous with that of the intestine (Fig. 285). In 
 embryos of 2 to 3 mm. the liver anlage arises from the ventral side of the 
 intestine near the stomach, that is, from that. part of the intestine which is to 
 become the duodenum. In embryos of 3 to 4 mm. the pancreas anlage arises 
 in the same region, in part from the liver evagination and in part from the dorsal 
 side of the intestine (Fig. 285). 
 
 The intestine as a whole is suspended in the abdominal cavity by the dorsal 
 mesentery which is attached to the dorsal body \vall and which is continuous 
 with the dorsal mesogastrium. A ventral mesentery, continuous with the 
 ventral mesogastrium, is present only at the cephalic end of the duodenum 
 (Fig. 301). 
 
 The further development of the intestine, apart from histogenesis, consists 
 very largely of the formation of loops and coils, due to an enormous increase in 
 the length of the tube. The abdominal cavity at the same time enlarges to 
 accommodate the increased bulk. As the stomach changes its position (p. 336), 
 the duodenum comes to lie obliquely across the body and forms a curve with the 
 concavity directed dorsally (Fig. 301). The rest of the intestine forms a loop 
 which extends ventrally and caudally as far as the umbilicus. The arms of the 
 loop are almost parallel and the cephalic arm lies a little to the left of the caudal. 
 The apex of the loop extends into the umbilical coelom and is attached to the yolk 
 stalk. From the dorsal end of the caudal arm the intestine extends directly 
 to the caudal end of the body (Fig. 301). 
 
 Soon after the loop is formed a small evagination appears on its caudal arm, 
 not far from the apex. This is the anlage of the cacum and marks the bound- 
 
338 TEXT-BOOK OF EMBRYOLOGY. 
 
 ary between the small and large intestine (Fig. 301). At this stage, therefore, 
 all the great divisions of the intestinal tract are distinguishable, viz. : the duodenum 
 with the ducts of the liver and pancreas; the mesenterial small intestine with the 
 yolk stalk; and the colon extending from the caecum to the caudal end. There 
 are, however, practically no differences between the regions, either in structure 
 or in size. 
 
 In further development the duodenum comes to lie more nearly transversely 
 across the body, thus assuming its adult position. Its mesentery fuses with the 
 peritoneum of the dorsal body wall and the duodenum thus becomes a fixed 
 portion of the intestinal tract (p. 380; also Fig. 339). It enlarges a little more 
 
 Portal vein - 
 
 Foramen of 
 Winslow 
 
 FIG. 302. Reconstruction of the liver and intestine of a human embryo of 17 mm. Mall. 
 
 G.B., gall bladder; H. V., hepatic vein; U.V., umbilical vein; 1-6, primary bends in the long 
 
 intestinal loop; i represents the duodenum. 
 
 rapidly than the rest of the small intestine and acquires a greater diameter. In 
 embryos of 12 to 13 mm. the lumen becomes obliterated by an overgrowth of the 
 mucous membrane caudal to the ducts of the liver and pancreas. In embryos 
 of about 15 mm., however, the lumen reappears. It seems difficult to find a 
 cause for this peculiar growth of the mucosa. 
 
 Very shortly after the formation of the long loop in the intestine, six bends 
 become recognizable in the portion between the stomach and the apex of the 
 loop (Fig. 302). These bends later form distinct loops which are destined to 
 become definite parts of the small intestine. The first loop is the duodenum, 
 the development of which has already been considered, and which maintains 
 practically its original position. The other five loops continue to elongate and 
 form secondary loops, all of which push their way into the umbilical coelom 
 
DEVELOPMENT OF THE ALIMENTARY TUBE AND APPENDED ORGANS. 339 
 
 where they remain until the embryo reaches a length of 40 mm. (compare Figs. 
 303 and 304) . Then they return very quickly to the abdominal cavity proper. 
 
 After their return, the primary loops, with the secondary loops derived from 
 them, come to occupy fairly constant positions. The second and third move 
 to the left upper part of the abdominal cavity; the fourth crosses the medial 
 line and occupies the right upper part. The fifth crosses back and lies in the 
 left iliac fossa; the sixth lies in the pelvis and lower part of the abdominal 
 cavity (Fig. 305). 
 
 Certain variations may occur but are usually not considered as abnormal. 
 The most frequent variation is one in which the fourth coil, along with the 
 
 FIG. 303. Reconstruction of the stomach and intestine of a human embryo of 28 mm. Mall. 
 
 The numbers are placed on the coils derived from the primary bends as shown in 
 
 Fig. 302; i represents the duodenum. 
 
 second and third, lies on the left side, its usual position on the right being oc- 
 cupied by the ascending colon. Xot uncommonly the positions of the fourth 
 and the second and third are reversed. Less commonly extra loops are formed. 
 
 Usually the proximal part of the yolk stalk disappears during fcetal life. In 
 a few cases, however, it persists as a blind sac of variable length, known as 
 MeckePs diverticulum (see also p. 113). 
 
 Even before the loops return to the abdominal cavity the colon or large 
 intestine increases in diameter more rapidly than the small intestine. After 
 the return, the caecum is carried across to the right side and comes to lie just 
 caudal to the liver. From the caecum the colon extends across the abdominal 
 
340 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 cavity, ventral to the duodenum, forming the transverse colon. It then de- 
 scends on the left side as the descending colon which passes over into the sigmoid 
 colon (Fig. 337). The transverse, the descending and the sigmoid portions of 
 the colon are recognizable in the third month. Up to the time of birth the 
 sigmoid portion is disproportionately long; after birth the other portions 
 
 FIG. 304. Drawing from a reconstruction of a human embryo of 24 mm. Matt. 
 The intestinal coils lie for the most part in the umbilical ccelom. C, caecum; K, kidney; L, liver. 
 S, stomach; S. C., suprarenal gland; W, mesonephros; 12, twelfth thoracic nerve; 5, fifth 
 lumbar nerve. 
 
 grow relatively faster. After the fourth month the portion to which the caecum 
 is attached grows downward in the right side of the abdominal cavity, thus form- 
 ing the ascending colon (Fig. 342). 
 
 The caecum, which appears in very early stages as an evagination at the 
 junction of the small and large intestines, for a time continues to increase uni- 
 formly in size. Then the proximal end increases more rapidly than the distal, 
 and forms the caecum of adult anatomy. The distal end, failing to keep pace 
 
DEVELOPMENT OF THE ALIMENTARY TUBE AND APPENDED ORGANS. 341 
 
 in development, remains more slender and forms the vermiform appendix 
 (Fig. 305). 
 
 As has already been mentioned, the primitive gut ends blindly in the caudal 
 end of the embryo (Fig. 284). The anal opening is a secondary formation. 
 On the ventral side of the caudal end of the body there is formed a depression 
 known as the anal pit. The mesoderm at the bottom of the pit becomes thin- 
 ner until the ectoderm comes in contact with the entoderm on the ventral side 
 of the gut, thus forming the anal membrane. The area of contact is not at the 
 
 FIG. 305. Drawing from a model of the small intestine in the adult. Ventral view. Mall. 
 
 The intestinal coils are shown in the usual relative position. The numbers indicate the coils derived 
 
 from the primary bends in the foetus as shown in Figs. 302 and 303. 
 
 extreme end of the gut, but a short distance toward the allantoic duct. In the 
 meantime, the urogenital ducts come to open into that portion of the gut which 
 lies just cranial to the anal membrane. The gut enlarges in this region to 
 form the cloaca. The latter becomes separated by the urorectal fold into a 
 dorsal portion, the rectum, and a ventral portion, the urogenital sinus (Figs. 361 
 and 363). At about the time of separation (embryos of about 14 mm. or 
 thirty-six to thirty-eight days) the anal membrane ruptures and the anal open- 
 
342 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 ing is formed. The portion of the gut caudal to the anus, known as the caudal 
 gut, normally disappears. 
 
 Histogenesis of the Gastrointestinal Tract. 
 
 The wall of the primitive gut is composed of two layers the entoderm which 
 lines the lumen, and the splanchnic mesoderm which borders on the ccelom or body 
 cavity. While the germ layers are still flat, the entoderm is a single layer of flat 
 cells with bulging nuclei, but after the closure of the gut the cells become col- 
 umnar. The splanchnic mesoderm is composed of two layers the mesothe- 
 lium bordering on the ccelom, the cells of which gradually change from flat 
 
 Mesentery 
 
 
 Epithelium 
 
 Stroma 
 
 Mesothelium 
 
 Long. 
 Trans. J 
 
 muscle 
 
 FIG. 306. Transverse section of the small intestine of a pig embryo of 32 mm. Bonnet. 
 
 to rather high, and a number of indifferent, branching mesenchymal cells 
 lying between the mesothelium and entoderm. The entoderm is destined to 
 give rise to the general epithelial lining of the gastrointestinal tract and to all 
 the glands connected with it. The mesothelium around the gut forms a part of 
 the general mesothelial lining of the ccelom, its cells apparently changing back 
 to a flat type. The mesenchymal tissue is destined to give rise to all the con- 
 nective tissue and smooth muscle of the tract. The circular layer of muscle 
 appears first, the longitudinal next, both appearing during the third and fourth 
 months, and last of all the muscularis mucosae (Fig. 306). 
 
 THE Mucous MEMBRANE. The mucous membrane is formed by the 
 epithelium (entoderm) and the subjacent mesenchymal tissue. In its develop- 
 
DEVELOPMENT OF THE ALIMENTARY TUBE AND APPENDED ORGANS. 343 
 
 ment there are two factors to be considered: (i) The formation of folds to in- 
 crease the absorbing surface and (2) the formation of secreting organs or glands. 
 As to the relation between these two factors there is a difference of opinion. 
 Some hold that both kinds of structures are the result of the same formative 
 process, that is, that the glands are simply the depressions or pits formed by the 
 intersection of folds at various angles, and that the folds are produced primarily 
 by the growth of the epithelium and mesenchymal tissue into the lumen of the 
 gut. Others maintain that although the folds may be produced by the growth 
 of the epithelium and mesenchymal tissue into the lumen, the glands arise as 
 independent growths of the epithelium into the subjacent tissue. The latter 
 
 view is supported by the fact that in 
 some Amphibia the glands appear before 
 the folds (Fig. 307). Recent work on 
 Mammals also favors this view. 
 
 The development of the folds and 
 glands begins in the different parts of the 
 gastrointestinal tract at different times. 
 It begins first in the stomach, then in the 
 
 FIG. 307. Section through the wall of the . . . . . . . 
 
 stomach of a frog embryo. Ep., Epi- duodenum, then in the colon, and then 
 theiium, with glands; sfo. submucosa; j the jejunum whence it progresses 
 
 Muse., muscle layer. Ratner. J J 
 
 slowly into the ileum. In the stomach 
 
 it is uncertain whether the crypts and glands are depressions left among 
 projections of the mucous membrane, or the glands represent evaginations of 
 the epithelium into the underlying tissue. In the case of the large intestine 
 the same uncertainty exists. If the so-called glands are depressions among 
 villous projections that grow into the lumen of the intestine, they are not true 
 glands from an embryological point of view. 
 
 Studies of the development of the mill in the human small intestine have led 
 to the conclusion that they are formed primarily as growths of the mucosa into 
 the lumen. In embryos of 19 mm. the mucosa of the cephalic end is thrown 
 into a number of longitudinal folds (Fig. 308). These then develop pro- 
 gressively toward the caudal end. Beginning in embryos of 50 to 60 mm. the 
 longitudinal folds become broken transversely into conical structures, the 
 villi. The intestinal crypts (of Lieberkuhn) possibly represent outgrowths of 
 the epithelium from the bottoms of the intervillous spaces. The duodenal 
 (Brunner's) glands are possibly to be considered as a continuation of the pyloric 
 glands of the stomach. They apparently grow as evaginations from the 
 intervillous crypts. 
 
 The epithelial lining of the gastrointestinal tract is from the beginning a 
 single layer of cells, although the individual cells are altered in shape and 
 structure and acquire different functions in different regions. There is still 
 
344 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 some dispute as to whether the mucous cells are continuously being derived 
 from the other epithelial cells or, when once formed, reproduce themselves by 
 mitosis. As a matter of fact, mitosis has been observed in the mucous cells of 
 the stomach. 
 
 FiG. 308. From a reconstruction of the small intestine of a human embryo of 28 mm., showing the 
 longitudinal ridges which eventually become broken transversely to form the villi. Berry. 
 
 THE LYMPH FOLLICLES. In the development of the lymph follicles in the 
 gastrointestinal tract the same question arises as in the case of the tonsils and 
 thymus. Are the lymphoid cells of mesodermal or of entodermal (epithelial) 
 
 a 
 
 -^ 
 
 FIG. 309. Sections through the wall of the caecum of (a) a rabbit 2| days and (6) 5 days after 
 birth, showing the development of the lymph follicles. /. Lymphoid infiltration in the stroma; 
 r, wandering cells in the epithelium; z, lymphoid cells in the core of a villus. Stohr. 
 
 origin? Evidence at present favors the mesodermal origin. In the case of 
 Peyer's patches, collections of lymphoid cells appear near the blood vessels in 
 the stroma and neighboring parts of the submucosa. These increase in extent, 
 
DEVELOPMENT OF THE ALIMENTARY TUBE AND APPENDED ORGANS. 345 
 
 the lymphoid cells dividing actively, and grow into the bases of some of the 
 villi and deeper into the submucosa (Fig. 309). Germinal centers appear in 
 many of the follicles, and the surrounding stroma becomes densely infiltrated 
 with the lymphoid cells. Individual follicles may develop, in the manner 
 described, in any part of the gastrointestinal tract. The appendix especially is 
 the seat of extensive lymphatic tissue formation. It is stated in the section on 
 the lymphatic system that lymph glands may arise at any time in any region as 
 the result of unusual conditions (p. 282), and this also holds true in the case of 
 lymph follicles in the digestive tract. 
 
 The Development of the Liver. 
 
 The liver is the first gland of the digestive tract to appear. In embryos of 
 about 3 mm. a longitudinal ridge-like evagination develops from the entoderm 
 on the ventral side of the gut a short distance caudal to the stomach, that is, in 
 
 Myotome 
 Aorta 
 
 Post, cardinal vein 
 Coelom 
 
 Upper limb bud 
 Dorsal mesentery 
 
 Duodenum 
 Liver 
 
 Omphalomesenteric vein 
 Umbilical vein 
 
 Heart 
 
 FIG. 310. Transverse section of a human embryo of 5 mm., showing the liver evagination and the 
 breaking up of the omphalomesenteric veins by the hepatic cylinders. Photograph. 
 
 the duodenal portion of the gut (Figs. 285, 310, 311). The cephalic part of the 
 evagination is solid and, being destined to give rise to the liver proper, is called the 
 pars hepatica. The caudal part is hollow, its cavity being continuous with the 
 lumen of the gut, and is destined to give rise to the gall bladder, whence it is 
 called the pars cystica. Beginning at both the cephalic and caudal ends, the 
 evagination as a whole becomes constricted from the gut until (in embryos of 
 about 8 mm.) its only connection with the latter is a narrow cord of cells which 
 
346 TEXT-BOOK OF EMBRYOLOGY, 
 
 is the anlage of the ductus choledochus. The pars hepatica by this time has 
 enlarged considerably and remains attached to the ductus choledochus by a 
 short cord of cells, the anlage of the hepatic duct. The pars cystica has also 
 become larger, its distal portion being somewhat dilated, and is connected with 
 the ductus choledochus by the anlage of the cystic duct (Figs. 312 and 313). 
 The pars cystica grows into the ventral mesentery and thus becomes sur- 
 rounded by mesodermal tissue. The proximal portion continues to elongate to 
 form the cystic duct and the distal portion becomes larger and more dilated to 
 form the gall bladder. 
 
 D. pan. 
 
 V. pan. 
 
 ^%fa .^^^..^^^^^v 
 
 D.ch. 
 
 H.du. 
 
 G.bl. 
 
 FIG. 311. From a model of the duodenum and the primary evaginations of the 
 
 liver and pancreas in a 5 mm. sheep embryo. Stoss. 
 
 D.pan., Dorsal pancreas; Du., duodenum; D. ch., ductus choledochus; G. bl., gall 
 bladder; H. du., hepatic duct. 
 
 The pars hepatica, or anlage of the liver proper, also grows into the ventral 
 mesentery, thus becoming surrounded by mesodermal tissue. As stated in 
 connection with the development of the diaphragm, the portion of the mesen- 
 tery into which the liver grows is involved in the formation of the septum 
 transversum (p. 374). Thus the developing liver becomes enclosed in the 
 septum (Fig. 330). The mesodermal tissue gives rise to the fibrous capsule of 
 Glisson and to the small amount of connective tissue within the gland. 
 
 Although the liver develops as a series of outgrowths from the original 
 evagination, there are certain features in its development which distinguish it 
 from glands in general. The outgrowths come in contact with the omphalomes- 
 enteric veins which are situated in the ventral mesentery (p. 260). They push 
 their way into and through the veins, breaking them up into smaller channels 
 (Fig. 310). They anastomose freely with one another, and the veins send off 
 
DEVELOPMENT OF THE ALIMENTARY TUBE AND APPENDED ORGANS. 347 
 
 branches which circumvent them. Thus there is formed a network of trabec- 
 ulae of liver cells, called hepatic cylinders, the meshes of which are filled with blood 
 vessels. Therefore the liver is distinguished from other glands in general in 
 
 Stomach 
 
 Left hep. 
 duct 
 
 [ Dors, pancreas 
 
 'A Vent, pancreas 
 
 Duodenum 
 
 FIG. 312. From a reconstruction of the anlagen of the liver and pancreas and a part of the 
 stomach and duodenum of a human embryo of 4 weeks. Felix. 
 
 that the hepatic cylinders, which are comparable with the smaller ducts and 
 terminal tubules of other glands, anastomose, and in that the blood vessels are 
 broken up by the growth of these cylinders. 
 
 4 
 
 FIG. 313. From a reconstruction of the anlagen of the liver and pancreas and the stomach 
 
 of a human embryo of 8 mm. Hammar. 
 
 D.P., Dorsal pancreas; Du., duodenum; D. V., ductus venosus; G.B., gall bladder; 
 R.I., right lobe of liver; ., stomach; V.P., ventral pancreas. 
 
 This mode of development establishes what is known as a sinusoidal circulation, which 
 differs from the ordinary capillary circulation. The sinusoids are produced by the growth 
 of the trabeculse of the developing organ into large vessels and the breaking up of the latter 
 
348 
 
 TEXT-BOOK OF EMBRYOLOGY, 
 
 into smaller vessels. It is obvious that a sinusoidal circulation is purely venous or purely 
 arterial. Furthermore, development of this nature leaves comparatively little connective 
 tissue within the gland, another feature characteristic of the liver. 
 
 All the blood carried to the liver by the omphalomesenteric veins must 
 follow the tortuous course of the sinusoids before being collected again and 
 passed on to the heart. When the umbilical veins come into connection with 
 the liver they also join in the sinusoidal circulation. Subsequently, however, a 
 more direct channel the ductus venosus is established and persists for a 
 
 Right side 
 
 Suprarenal glands 
 Mesonephros 
 
 Dorsal mesogastrium 
 (greater omentum) 
 
 Stomach 
 
 Ventral mesogastrium 
 (lesser omentum) 
 
 Liver 
 
 Left side 
 
 FlG. 314. Tranverse section of a 14 mm. pig embryo, through the region of the stomach. 
 Photograph. The arrow points into the bursa omentalis. 
 
 short time. This is probably due to the large volume of blood brought in by 
 the umbilical veins. Finally the ductus venosus disappears and the sinusoidal 
 circulation remains as the permanent form. (For the development of the veins 
 in the liver see p. 259.) 
 
 The lobes of the liver develop in a general way in relation to the great 
 venous trunks which at one time or another pass into or through the gland. 
 The anlage of the organ grows into the ventral mesentery, subsequently be- 
 coming enclosed in the septum transversum. In so doing it encounters the 
 omphalomesenteric veins, and forms, in relation to the latter, two incompletely 
 separated parts which have been called the dorso-lateral lobes. When the 
 umbilical veins enter the liver a more ventral, medial mass is formed. This 
 becomes incompletely separated into two parts which give rise to the permanent 
 
DEVELOPMENT OF THE ALIMENTARY TUBE AND APPENDED ORGANS. 349 
 
 right and left lobes. The right becomes the larger. The right umbilical vein 
 loses its connection with the liver (p. 261). After birth the left, which lies be- 
 tween the right and left lobes, degenerates into the round ligament of the liver, 
 The other lobes arise secondarily as outgrowths from the right primary dorso- 
 lateral lobe, the caudate (lobe of Spigelius) from its inner (medial) surface, 
 the quadrate from its dorsal surface. 
 
 The liver as a whole grows rapidly and by the second month is relatively 
 large. During the third month it fills the greater part of the abdominal cavity. 
 After the fifth month it grows less rapidly and the other intraabdominal organs 
 overtake it, so to speak, although at birth it forms one-eighteenth the total 
 weight of the body. After birth it actually diminishes in size. The right lobe 
 is from the beginning larger than the left, and after birth the predominance 
 increases. 
 
 His to genesis of the Liver. The hepatic part (pars hepatica) of the 
 liver anlage is derived from the entodermal lining of the gut and constitutes a 
 mass of cells with no lumen. From this mass, solid bud-like evaginations grow 
 into the mesentery, break up the omphalomesenteric veins into smaller channels 
 and form trabeculae, or hepatic cylinders (p. 347). The latter anastomose 
 freely with one another and are composed of polyhedral, darkly staining cells 
 with vesicular nuclei (Fig. 315, A). Lumina begin to appear in the cylinders 
 about the fourth week as small cavities which communicate with the cavity of 
 the gut. 
 
 The hepatic cylinders are the forerunners of the hepatic cords or cords of 
 liver cells. There are two views as to the manner of transformation. The 
 older view is that the cylinders gradually become stretched, the number of cells 
 in cross-section becoming less until it is reduced to two. Between these two 
 lies the lumen of the cord or the so-called "bile capillary" (Fig. 315, B). The 
 other view is that branches from the sinusoids grow into the cylinders and sub- 
 divide them into hepatic cords. 
 
 As stated above, the hepatic cylinders are at first composed of darkly stain- 
 ing, polyhedral cells with vesicular nuclei. These are the liver cells proper. 
 Later other small spherical cells, with dense nuclei, appear and during the 
 fourth month become very numerous (Fig. 315, A). From this time on, they 
 grow less in number and at birth have practically disappeared. Earlier investi- 
 gators considered them as developing liver cells. Further study on the develop- 
 ment of the blood, however, has led others to consider them as erythroblasts 
 (p. 270). Since they are inside of the hepatic cylinders, they either wander in 
 from the intertrabecular blood vessels or lie in intratrabecular vessels. The 
 latter supposition accords with the view that the cylinders are broken up into 
 hepatic cords by the ingrowth of branches from the sinusoids. 
 
 The development of the lobules of the liver, producing the peculiar relations 
 
350 
 
 TEXT-BOOK OF EMBRYOLOGY^ 
 
 between the parenchyma of the gland and the blood vessels, has not been 
 clearly and completely demonstrated. In young embryos the branches of the 
 hepatic veins are surrounded by comparatively little connective tissue. The 
 branches of the portal vein are surrounded by a considerable amount which 
 subdivides the liver into lobules but not in the same manner as in the adult. 
 The trabeculae possess no radial character and there are several so-called central 
 veins in each lobule. The changes by which these primary lobules are sub- 
 divided into the permanent ones do not take place until after birth. The 
 branches of the portal vein, with the surrounding connective tissue, invade the 
 
 A 
 
 FIG. 315. Sections of the liver of (A) a human foetus of 6 months and (B) a child of 4 years. 
 
 Toldt and Zuckerhandl. McMurrich. 
 bc s . Bile "capillary"; e, erythroblast; he, hepatic cylinder (in A), cord of liver cells (in B). 
 
 primary lobules and divide them into a number of secondary lobules, corre- 
 sponding to the original number of central veins. At the same time the hepatic 
 cords (which have been formed meanwhile) become arranged radially around 
 the central veins in the characteristic manner. The hepatic artery grows into 
 the liver secondarily and its branches follow the course of the branches of the 
 portal vein. 
 
 Degeneration of the liver cells occurs in the region of the left triangular liga- 
 ment, the gall bladder and the inferior vena cava. The bile ducts may, how- 
 ever, withstand the degenerative processes and persist as the vasa aberrantia of 
 the liver. The cause of the degeneration is possibly the pressure brought to 
 bear by other organs. 
 
 The Development of the Pancreas. 
 
 The epithelium of the pancreas, like that of the liver, is a derivative of the 
 entoderm. It arises from two (or three) separate anlagen, one dorsal and one 
 
DEVELOPMENT OF THE ALIMENTARY TUBE AND APPENDED ORGANS. 351 
 
 (or two) ventral. The dorsal anlage appears first as a ridge-like evagination 
 from the dorsal wall of the gut, slightly cranial to the level of the liver (Figs. 311 
 and 312). It appears about the same time as the liver or a little later. The 
 mass of cells grows into the dorsal mesentery and becomes constricted from 
 the parent epithelium except for a thin neck which becomes the duct of 
 Santorini (Fig. 316). A little later two other diverticula appear, one from each 
 side of the common bile duct. It is uncertain whether only one or both of these 
 
 Stomach 
 
 Liver 
 
 Cystic duct 
 
 Dorsal pancreas - 
 
 Gall bladder 
 
 Ductus choledochus 
 Ventral pancreas 
 
 Ductus choledochus 
 
 Liver 
 
 Dorsal pancreas 
 
 Acces. pancr. duct 
 (Santorini) 
 
 Duodenum 
 
 Cystic duct 
 
 Gall bladder 
 
 Ventral pancreas with 
 pancr. duct (Wirsung) 
 FIG. 317. 
 
 FIGS. 316 and 317. From models of the developing liver and pancreas of rabbit embryos of 
 8 mm. and 10 mm , respectively-. Both seen from the right side. Hammar, Bonnet. 
 
 take part in the formation of the pancreas, but it seems most probable that the 
 left one disappears entirely. The right diverticulum continues to develop and 
 becomes constricted from the parent epithelium, leaving only a thin neck which 
 becomes the duct of Wirsung. 
 
 The smaller ventral pancreas grows to the right and then dorsally in the 
 mesentery (Fig. 318), passing over the right surface of the portal vein, until it 
 meets and fuses with the proximal part of the larger dorsal pancreas. The 
 fusion takes place in the sixth week, and the two anlagen then form a single 
 
352 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 mass. A communication is established between the two ducts, and the dorsal 
 duct (Santorini) usually disappears, leaving the ventral (Wirsung) as the per- 
 manent duct opening into the ductus choledochus. In a general way it may be 
 said that the ventral anlage gives rise to the head, the dorsal anlage to the body 
 and tail of the pancreas (compare Figs. 316 and 317). 
 
 As the pancreas grows into the dorsal mesentery it comes to lie in the 
 dorsal mesogastrium between the greater curvature of the stomach and the 
 vertebral column, and since the dorsal mesogastrium at first lies in the medial 
 sagittal plane, the pancreas is similarly situated. After the sixth week, how- 
 ever, as the stomach changes its position (p. 335), the pancreas is carried along 
 
 Inf. vena cava 
 
 Coelom 
 
 Dorsal pancreas 
 
 Portal vein 
 
 Ventral pancreas 
 
 Ductus choledochus 
 
 Right side 
 
 Mesonephros 
 
 Greater omentum 
 (dorsal mesentery) 
 
 Duodenum 
 
 Liver 
 
 Lft side 
 
 FIG. 318. From a transverse section through the region of the duodenum of a pig 
 embryo of 14 mm. Photograph. 
 
 with the mesogastrium and comes to lie in a transverse plane, with its head to 
 the right and embedded in the bend of the duodenum, and its tail reaching to 
 the spleen on the left. The organ as a whole is at first movable along with the 
 mesentery, but when it assumes its transverse position it lies close to the dorsal 
 abdominal wall. The mesentery then fuses with the adjacent peritoneum 
 (see p. 380), and the pancreas is firmly fixed. 
 
 The connective tissue of the pancreas is derived from the mesodermal tissue 
 of the mesentery. As the processes or buds which form the ducts and terminal 
 tubules grow out from the primary masses, they penetrate the mesodermal 
 tissue and are surrounded by it. Groups of tubules form lobes and lobules, 
 and the entire gland is surrounded by a capsule of connective tissue. 
 
DEVELOPMENT OF THE ALIMENTARY TUBE AND APPENDED ORGANS. 353 
 
 Histogenesis of the Pancreas. The masses of entodermal cells forming 
 the anlagen of the pancreas develop further by a process of budding, which 
 goes on until finally a compound tubular gland is produced. According to 
 
 FIG. 319. Sections of the developing pancreas of a guinea-pig embryo of 12 mm. (a); 
 
 of 33 mm. (6) ; of Torpedo marmorata (c) . Helly. 
 
 c, Capillaries; Dg, ducts; Gz, duct cells; Lz, Langhans' cells. The cells in c show- 
 distinct zymogen granules 
 
 some investigators the primary evaginations are hollow, their lumina being 
 continuous with the lumen of the gut. According to others they are solid at 
 first and acquire their lumina secondarily. The same uncertainty exists in 
 regard to the later outgrowths or buds. 
 
354 TEXT-BOOK OF EMBRYOLOGY. 
 
 The early entodermal cells proliferate, and the resulting cells change ac- 
 cording to their position in the gland. Those lining the larger ducts become 
 high columnar, with more or less homogeneous cytoplasm; those lining the 
 intermediate (intercalated) ducts become low; those lining the terminal secret- 
 ing tubules become pyramidal and more highly specialized, and also acquire 
 certain constituents the zymogen granules (Fig. 319, c) which vary with the 
 functional activities of the gland. The centro-tubular cells in the terminal 
 tubules are probably to be explained on a developmental basis. While a few 
 maintain that they are "wandering" cells, it is quite generally accepted 
 that they are simply continuations of the flat cells lining the intermediate 
 ducts, the result being that the cells of the terminal tubules seem to 
 spread out over the ends of the intermediate ducts in the form of cap-like 
 structures. 
 
 It was once thought that the islands of Langerhans were derived from the 
 mesodermal tissue. Recently it has been pretty clearly demonstrated that they 
 are derived from entoderm. In guinea-pig embryos of 5 to 6 mm., at a time 
 when the dorsal pancreas has merely begun its constriction from the gut, certain 
 cells in the mass appear darker and slightly larger than the others. They show 
 darker areas of cytoplasm around the nuclei, and later the darker areas extend 
 throughout the cells and the nuclei become larger and more vesicular. When 
 lumina appear in the outgrowths or buds, these cells occupy a position on or near 
 the surface of the buds (Fig. 319, a). In further development they tend to sepa- 
 rate themselves from the buds and collect in clumps (Fig. 319, b). Capillaries 
 then penetrate the clumps and break them up into the trabeculae of cells char- 
 acteristic of the islands of Langerhans (Fig. 3 1 9, c) . Studies on the development 
 of the islands in the human pancreas indicate a similar origin and mode of 
 development. 
 
 Anomalies. 
 
 One of the most striking anomalies of the organs of alimentation is found 
 in connection with a more general anomalous condition known as transposition 
 of the viscera (situs viscerum inversus). The transposition may be so complete 
 that the minor asymmetries normally present on the two sides are all repeated 
 in reverse order, the functions of the organs being unimpaired. As regards the 
 alimentary tract, this means that the position of the stomach is reversed in the 
 abdominal cavity; that the duodenum crosses from left to right; that the various 
 coils of the jejunum and ileum occupy positions opposite to the normal; that the 
 caecum and ascending colon are situated on the left side and the descending 
 colon on the right; and that the larger lobe of the liver lies on the left side. The 
 other visceral organs are transposed accordingly, the heart being inclined to- 
 ward the right side, the left lung consisting of three lobes and the right of two, 
 
DEVELOPMENT OF THE ALIMENTARY TUBE AND APPENDED ORGANS. 355 
 
 the left kidney being lower than the right, etc. Such cases are not uncommon, 
 two hundred being on record. 
 
 Various theories as to the causes of transposition of the organs have been 
 advanced. In the most plausible of these the anomalous condition is consid- 
 ered as due to the influence of the large veins in the embryo. It seems best, 
 therefore, to consider first the transposition of the heart (dextrocardia, referred 
 to on page 286). 
 
 After the two anlagen unite in the midventral line, the heart constitutes a 
 simple straight tube which lies in a longitudinal direction in the primitive peri- 
 cardial cavity, and which is joined caudally by the two omphalomesenteric 
 veins and cranially by the ventral aortic trunk (p. 228). Normally the left 
 omphalomesenteric vein is the larger and pours a greater quantity of blood into 
 the heart tube than the right. This condition is regarded as the primary factor 
 in the deflection of the tube toward the right side (p. 230; also Fig. 196). If the 
 conditions were reversed, that is, if the right omphalomesenteric vein were the 
 larger and poured the greater quantity of blood into the heart tube, the pri- 
 mary bend of the latter would be toward the left side. Consequently the heart 
 would continue to develop in the transposed position and eventually come to 
 lie on the side opposite to the normal. 
 
 Although dextrocardia is very frequently associated with transposition of 
 the abdominal organs, it is not necessarily so, for there are cases of the latter in 
 which the heart occupies the normal position. Consequently it seems that 
 further influences must be present to account for transposition of the abdominal 
 organs when the thoracic organs are normal. A number of investigators have 
 emphasized the importance of the influence of the large venous trunks in the 
 abdominal region, especially on the position of the liver and stomach. 
 
 Primarily the omphalomesenteric veins pass cranially through the mesen- 
 tery. Later they form two loops or rings around the duodenum. Then the 
 left half of the upper ring and the right half of the lower disappear, the common 
 venous trunk thus following a spiral course around the duodenum (p. 262; also 
 Fig. 239). This primary relation of the omphalomesenteric vein is retained in 
 the relation of the portal vein to the duodenum. The stomach lies to the left 
 of the portal vein. After the allantoic (placental) circulation is established the 
 umbilical veins pass cranially in the lateral body walls. After the veins come 
 into connection with the liver, the right atrophies and the left increases in size 
 and becomes the single large umbilical vein of later stages (p. 261; also Fig. 240). 
 The right lobe of the liver becomes the larger. 
 
 If, as is maintained by some investigators, the usual position of the stomach 
 and liver is due to the persistence of the left venous trunks, a persistence of the 
 right venous trunks would afford a plausible explanation of the transposition of 
 these organs. It is not unreasonable to attribute also the transposition of the 
 
356 TEXT-BOOK OF EMBRYOLOGY. 
 
 other abdominal organs directly or indirectly to the persistence of the right 
 venous trunks. Certainly a reversal in the position of the stomach would 
 cause a reversal in the position of the duodenum. 
 
 If these conditions are the real ones, the fact that the thoracic organs can be 
 transposed without a transposition of the abdominal organs, or vice versa, 
 is accounted for. The primary bend of the heart tube occurs at a very early 
 period, before the changes in the vessels in the region of the liver. Conse- 
 quently a reversal of the conditions of the omphalomesenteric at a very early 
 stage only would be likely to affect the heart. The principal changes in size 
 of the venous trunks in the abdominal region take place after their channels 
 have been broken up in the liver. In other words, the modifications in the veins 
 in the liver occur after the definite relations of the heart have been established. 
 Therefore the transposition of the abdominal organs may take place after the 
 heart has begun to develop normally. 
 
 THE MOUTH. Anomalies in the mouth region, due to defective fusion of 
 the processes that bound it, have been considered elsewhere (p. 212). 
 
 Anomalies of the tongue sometimes arise as the result of imperfect develop- 
 ment of one or more of its anlagen. Imperfect development of the tuberculum 
 impar results in total or partial lack of the anterior part. Defects in the root 
 are probably due to imperfect development of one or both of the paired anlagen 
 (p. 320). Malformations of the lower jaw (micrognathus, agnathus) are 
 usually accompanied by malformations of the tongue, both structures being 
 derived largely from the first pair of branchial arches. 
 
 THE PHARYNX. The pharynx is the seat of cysts, fistulae and diverticula 
 which have been considered in connection with the anomalies in the region of 
 the branchial arches and grooves (Chap. XIX) . 
 
 The ihyreoid gland is not infrequently the seat of certain anomalies that 
 arise as the result of abnormal development. Persistent portions of the thyreo- 
 glossal duct, the upper end of which is indicated by the foramen cascum linguae, 
 may give rise to cystic structures extending to the region of the hyoid bone. 
 Persistent portions of the duct may even give rise to accessory thyreoid (supra- 
 hyoid, prehyoid) glands (p. 332; also Fig. 298). Considerable variation also 
 exists in the isthmus and lateral lobes of the thyreoid, due to variation in the 
 manner of development of the medial anlage. 
 
 Impaired development of the thymus gland sometimes leads to cysts which 
 come to lie in the anterior mediastinum. 
 
 THE (ESOPHAGUS. Very rarely the oesophagus is entirely lacking, being 
 represented by a mere cord of tissue. More frequently it is defective in certain 
 parts. The atresia may begin just below the pharynx or just above the stomach, 
 the intermediate portion being composed of a cord of fibrous tissue. Occasion- 
 ally the non-atretic portion opens into the trachea. Possibly this represents 
 
DEVELOPMENT OF THE ALIMENTARY TUBE AND APPENDED ORGANS. 357 
 
 an imperfect separation between the primitive gut and the anlage of the 
 respiratory system (p. 360). 
 
 THE STOMACH. Occasionally the stomach is smaller than the normal. It 
 may even be a narrow tube resembling the other portions of the gut, owing to 
 lack of dilatation. Other congenital malformations, apart from transposition 
 (p. 354), are very rare. 
 
 THE INTESTINES. One of the most common anomalies is the persistence of 
 the proximal end of the yolk stalk, forming Meckel's diverticulum (see p. 113). 
 This usually is attached to the ileum about three feet from the caecum. In ex- 
 ceptional cases it retains its lumen and, when the stump of the umbilical cord 
 disappears, forms a congenital umbilical fistula. Usually, however, the diver- 
 ticulum is shorter and ends blindly. Occasionally it becomes constricted from 
 the intestine and forms a cystic structure. (See also Chap. XIX.) 
 
 Congenital stenosis and atresia may occur in different regions of the intestine, 
 the duodenum being the most common site. Normally the lumen of the 
 duodenum becomes closed for a brief period during development (p. 338), and 
 congenital closure of the lumen may represent a persistence of the early em- 
 bryonic condition. 
 
 A conspicuous malformation is the persistence of the cloaca. The septum 
 which normally separates the latter structure into rectum and urogenital sinus 
 fails to develop, thus leaving a common cavity (see Figs. 361 and 362). In 
 addition to this the cloacal membrane may fail to rupture and the cloaca be- 
 come much distended. More often the septum develops in part, leaving only 
 a small opening between the rectum and urogenital sinus. After the latter 
 undergoes further development, the rectum comes to open into the urethra or 
 bladder, or into the vagina or uterus. 
 
 Atresia of the anus is not infrequently met with. The cloacal (or anal) 
 membrane fails to rupture and the rectum ends blindly. In other cases the 
 rectum opens into the urogenital sinus, as described in the preceding paragraph. 
 Occasionally the lumen of the rectum is closed atresia recti and the gut ends 
 blindly some distance from the surface, being connected with the anal region by 
 a cord of fibrous tissue. 
 
 Variations in the position of the intestinal loops, apart from transposition (p. 
 ?54^, are of frequent occurrence. It is not customary to include these varia- 
 tions among malformations (see p. 339). The caecum (and appendix) and colon 
 present some striking variations. The caecum may be situated high up in the 
 abdominal cavity, the ascending colon being absent. Or it may be situated at 
 any intermediate point between that and its usual position in the right iliac 
 fossa. These variations are due to different degrees of development of the 
 ascending colon (p. 340). 
 
 THE LIVER. Congenital malformations of the liver are rare. The most 
 
358 TEXT-BOOK OF EMBRYOLOGY. 
 
 frequent, apart from transposition, include anomalies in the size and number of 
 lobes. Accessory lobes may occur within the falciform ligament. One case 
 of lack of development of the gall bladder has been observed. Stenosis of the 
 bile passages is occasionally met with. 
 
 THE PANCREAS. Occasionally accessory glands are found in the intesti- 
 nal or gastric wall. These probably represent aberrant portions of the main 
 gland, and may give rise to cystic structures. Very recently, however, a 
 number of intestinal diverticula have been observed in certain mammalian 
 embryos and also in human embryos. Although the history of these unusual 
 diverticula has not been traced, their presence may offer a clue to the origin of 
 accessory pancreatic structures. The ducts of the pancreas are subject to 
 distinct variations, which, however, are not usually considered as anomalies. 
 Not infrequently the duct of the dorsal anlage (duct of Santorini) persists and 
 opens directly into the duodenum. It may persist along with the duct of the 
 ventral anlage (duct of Wirsung), or the latter may disappear (p. 352; compare 
 Figs. 316 and 317). 
 
 References for Further Study. 
 
 BELL, E. T.: The Development of the Thymus. American Jour, of Anat., Vol. V, 1906 
 
 BERRY, J. M.: On the Development of the Villi of the Human Intestine. Anat. Anz. 
 Bd. XVI, 1900. 
 
 BONNET, R.: Lehrbuch der Entwickelungsgeschichte. Berlin, 1907. 
 
 BORN, G.: Ueber die Derivate der embryonalen Schlundbogen und Schlundspalten bei 
 Saugetiere. Arch. f. mik. Anat., Bd. XXII, 1883. 
 
 BRACHET, A.: Die Entwickelung und Histogenese der Leber und des Pancreas. Ergeb- 
 nisse der Anat. u. Entwick., Bd. VI, 1897. 
 
 CHIEVITZ, J. C.: Beitrage zur Entwickelungsgeschichte der Speicheldrusen. Arch. /. 
 Anat. u. PhysioL, Anat. Abth., 1885. 
 
 CHORONSCHITZKY: Die Entstehung der Milz, Leber, Gallenblase, Bauchspeicheldruse 
 und des Pfortadersystems bei den verschiedenen Abteilungen der Wirbeltiere. Anat. Hefte, 
 Bd. XIII, 1900. 
 
 Fox, H.: The Pharyngeal Pouches and their Derivatives in the Mammalia. Am. Jour. 
 of Anat., Vol. VIII, No. 3, 1908. 
 
 FUSARI, R.: Sur les phenomenes, que Ton observe dans la muqueuse du canal digestif 
 durant le developpement du foetus humain. Arch. ital. BioL, T. XLII, 1904. 
 
 GOPPERT, E.: Die Entwickelung des Mundes und der Mundhohle mit Driisen und 
 Zunge; die Entwickelung der Schwimmblase, der Lunge und des Kehlkopfes der Wirbeltiere. 
 In Hertwig's Handbwh der vergleich. u. experiment. Entwickelungslehre der Wirbeltiere. Bd. 
 II, Teil I, 1902. 
 
 HAMMAR, J. A.: Einige Plattenmodelle zur Beleuchtung der friiheren embryonalen 
 Leberentwickelung. Arch. /. Anat. u. PhysioL, Anat. Abth., 1893. 
 
 HAMMAR, J. A.: Allgemeine Morphologic der Schlundspalten beim Menschen. Entwick- 
 elung des Mittelohrraumes und des ausseren Gehorganges. Arch. /. mik. Anat., Bd. LIX, 
 1902. 
 
 HAMMAR, J. A.: Das Schicksal der zweiten Schlundspalte. Zur vergleichenden Env 
 
DEVELOPMENT OF THE ALIMENTARY TUBE AND APPENDED ORGANS. 359 
 
 bryologie und Morphologic der Tonsille. Arch. /. mik. Anat., Bd. LXI, 1903. 
 
 HELLY, K.: Studien iiber Langerhanssche Inseln. Arch. f. mik. Anat., Bd. LXVII, 
 1907. 
 
 HERTWIG, O. : Lehrbuch der Entwickelungsgeschichte der Wirbeltiere und des Menschen. 
 Jena, 1906. 
 
 HEXDRICKSOX, W. F.: The Development of the Bile Capillaries as Revealed by Golgi's 
 Method. Johns Hopkins Hasp. Bull., 1898. 
 
 His, W.: Anatomic menschlicher Embryonen. Leipzig, 1880-1885. 
 
 His, W.: Die Entwickelung der menschlichen und tierischen Physiognomien. Arch. f. 
 Anat. u. Physiol., Anat. Abth., 1892. 
 
 KOHN, A.: Die Epithelkorperchen. Ergebnisse der Anat. u. Enluick., Bd. IX, 1899. 
 
 KOLLMANN, J.: Die Entwickelung der Lymphknotchen in dem Blinddarm und in dem 
 Processus vermiformis. Die Entwickelung der Tonsillen und die Entwickelung der Milz. 
 Arch. f. Anat. u. Physiol., Anat. Abth., 1900. 
 
 KOLLMAXX, J.: Lehrbuch der Entwickelungsgeschichte des Menschen. Jena, 1898. 
 
 KOLLMANN, J.: Handatlas der Entwickelungsgeschichte des Menschen. Jena, 1907. 
 
 MALL, F. P.: Ueber die Entwickelung des menschlichen Darmes und seiner Lage beim 
 Erwachsenen. Arch. f. Anat. u. Physiol., Anat. Abth. Suppl., 1897. 
 
 MAURER, F.: Die Entwickelung des Darmsystems. In Hertwig's Handbuch der ver- 
 gleich. u. experiment. Entuickehmgslehre der Wirbeltiere., Bd. II, Teil I, 1902. 
 
 McMuRRicn, J. P.: The Development of the Human Body. Third Ed. Philadelphia, 
 1907. 
 
 PEARCE, R. M.: The Development of the Islands of Langerhans in the Human Embryo. 
 American Jour, of Anat., Vol. II, 1903. 
 
 PIERSOL, G. A.: Teratology. In Wood's Reference Handbook of the Medical Sciences, 
 Vol. VII, 1904. 
 
 POLZL, A.: Zur Entwickelungsgeschichte des menschlichen Gaumens. Anat. Hefte, 
 1905. 
 
 ROSE, C.: Ueber die Entwickelung der Zahne des Menschen. Arch. /. mik. Anat. t 
 Bd. XXXVIII, 1891. 
 
 STEIDA, A.: Ueber Atresia ani congenita und die damit verbundenen Missbildungen. 
 Arch. f. klin. Chir., Bd. LXX, 1903 
 
 STOHR, P.: Ueber die Entwickelung der Darmlymphknotchen und iiber die Riickbildung 
 von Darmdriisen. Arch. f. Anat. u. Physiol., Anat. Abth., 1898. 
 
 TAXDLER, J.: Zur Entwickelungsgeschichte des menschlichen Duodenum in friihen 
 Embryonalstadien. Morph. Jahrb., Bd. XXIX, 1900. 
 
 TOLDT und ZUCKERHAXDL: Ueber die Form und Texturveranderungen der mensch- 
 lichen Leber wahrend Wachsthums. Sitzungsber. d. kaiser. Akad. d. Wissensch., Wien. 
 Math.-Naturunss. Klasse., Bd. LXXII, 1875. 
 
 TOURXEUX ET VERDUN: Sur les premiers developpements de la Thyroide, du Thymus et 
 des glandes parathyroidiennes chez Phomme. Jour. de. I' Anat. et. de la Physiol., T. XXXIII, 
 1897. 
 
CHAPTER XIII. 
 THE DEVELOPMENT OF THE RESPIRATORY SYSTEM. 
 
 The anlage of the respiratory system appears in human embryos of about 
 3.2 mm. A hollow, linear evagination the lung groove develops on the 
 ventral side of the cesophageal portion of the primitive gut, extending caudally 
 a short distance from the region of the fourth inner branchial groove. It was 
 once thought that the evagination developed along practically the entire length 
 of the oesophagus anlage, but more recent researches seem to prove that it is 
 confined to the cephalic end. The lung groove soon becomes separated from 
 
 Pharynx 
 
 Hypophysis 
 
 Branchial arches 
 (pharynx) 
 
 Lung 
 
 Liver 
 
 Stomach 
 
 Pancreas 
 
 Common 
 mesentery 
 
 Mesonephros 
 Allantoic duct 
 
 Hind-gut 
 
 ^^ \^^^ w 
 
 Kidney bud 
 FIG. 320. Sagittal section of reconstruction of a human embryo of 5 mm. His, Kollmann. 
 
 the gut by a constriction which appears at the caudal end and gradually pro- 
 gresses forward. Thus there is formed a tube which lies ventral to the gut and 
 which opens upon the floor of the latter at the boundary line between the 
 oesophagus and pharynx (Figs. 320 and 284). 
 
 From this simple tube the entire respiratory system develops. The 
 cephalic end gives rise to the larynx, the opening into the gut being the aditus 
 laryngis. The middle portion gives rise to the trachea. Two outgrowths from 
 the caudal end of the tube, which appear about the time of separation from the 
 
 360 
 
THE DEVELOPMENT OF THE RESPIRATORY SYSTEM. 361 
 
 oesophagus, develop into the bronchi and their continuations the lungs. The 
 epithelial lining of the system is of course derived from the entoderm. The 
 various kinds of connective tissue are derived from the mesoderm, since the 
 anlage grows into the mesodermal tissue of the ventral mesentery. 
 
 The Larynx. 
 
 The opening from the gut into the respiratory tube becomes surrounded by 
 a U-shaped elevation thefurcula which lies in the floor of the pharynx with 
 its open end directed caudally. Toward the end of the first month each 
 side of the opening (aditus laryngis) becomes elevated, forming the arytenoid 
 ridge. From each of these a secondary elevation arises, forming the cunei- 
 form ridge. The arytenoid ridges come so close together that they practically 
 close the opening except at its cephalic side (Fig. 321). Along with the develop- 
 ment of these ridges the apical portion of the furcula becomes a distinct trans- 
 
 Tuberculum impar 
 i 
 
 ^B- Epiglottis 
 ^^^^^- Aryepiglottic ridge 
 
 -' 
 
 / &JT~ Arytenoid ridge 
 
 --/ I Cuneiform ridge 
 
 j Aditus laryngis 
 
 -__^_^_ Cuneiform ridge 
 
 A 
 
 FIG. 321. From a reconstruction of the larynx of a human embryo of 28 days. 
 Seen from above. Kallius. 
 
 verse fold at the cephalic rim of the opening. This fold is the anlage of the 
 epiglottis. Laterally the epiglottic fold becomes continuous with the arytenoid 
 ridges, forming the aryepiglottic ridges (Fig. 321). 
 
 During the fourth month a groove-like depression appears on the medial 
 side of each arytenoid ridge, gradually becomes deeper, and leaves on each side 
 of it a fold or lip which bounds the opening. The external lips those nearer 
 the pharynx form the superior or false vocal cords; the internal lips form the 
 true vocal cords. At the same time the opening into the larynx, which was 
 closed by the arytenoid ridges, is reestablished. The depression between the 
 vocal cords on each side becomes still deeper to form the ventricle, and a further 
 outgrowth from the ventricle produces the appendage of the ventricle (the laryn- 
 geal pouch). 
 
362 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 The mesodermal tissue external to the epithelium (entoderm) of the larynx 
 gives rise to the various kinds of connective tissue including the laryngeal 
 cartilages. By the end of the fourth week condensations appear in the mesen- 
 chymal tissue, which are the forerunners of the cartilages, but true cartilage 
 does not appear until the seventh week. The anlagen of the thyreoid cartilage 
 
 Sup. hy. 
 
 Inf. hy. 
 
 Thyr. 
 
 FIG. 322. From reconstructions of the mesenchymal condensations which represent the hyoid and 
 thyreoid cartilages in an embryo of 40 days. A, Ventral view; B, lateral view from right. 
 Kallius. 
 
 Inf.hy., Inferior (greater) horn of hyoid; Sup.hy., superior (lesser) horn of hyoid; Thyr., thyreoid. 
 The portions indicated by black lines represent chondrification centers. 
 
 are two mesenchymal plates, one on each side, which are bilaterally sym- 
 metrical and correspond to the lateral parts of the adult cartilage (Fig. 322, A). 
 These plates gradually grow ventrally and unite and fuse in the midventral 
 line (Fig. 323). Two centers of chondrification appear in each plate (Fig. 322, 4,) 
 
 Pharynx 
 
 . / Muscle 
 
 "' '.-. Arytenoid cartilage 
 
 i Thyreoid cartilage 
 
 Muscle 
 
 Copula 
 
 FIG. 323. From a transverse section through the pharynx and larynx of a human 
 embryo of 48 mm. Nicolas. 
 
 and enlarge until the entire plate is converted into cartilage, the middle part 
 becoming elastic in character, the rest hyalin. 
 
 Originally the cephalic edge of each thyreoid plate is connected with the 
 inferior horn of the hyoid cartilage (Fig. 322, B). This connection is subse- 
 quently lost, but a remnant of the connecting cartilage persists as the triticeous 
 
THE DEVELOPMENT OF THE RESPIRATORY SYSTEM. 363 
 
 cartilage in the lateral hyothyreoid ligament. The anlagen of the arytenoid 
 cartilages develop in the arytenoid ridges as condensations of the mesenchyme, 
 which later are converted into true cartilage (Fig. 323). The apex and vocal 
 process of each arytenoid become elastic, the main body becomes hyalin. 
 The corniculate cartilages (cartilages of Santorini) are split off from the cephalic 
 ends of the arytenoids and are of the elastic variety. The cricoid cartilage, 
 like the others, is preceded by a condensation of mesenchyme. Chondrifica- 
 tion begins on each side and then progresses around dorsally and ventrally until 
 a complete hyalin ring is formed. From its developmental resemblance to the 
 tracheal rings, the cricoid is sometimes regarded as the most cephalic of that 
 series. The epiglottic cartilage develops in the epiglottic ridge as two sepa- 
 rate pieces which subsequently fuse. It is of the elastic variety. The cuneiform 
 cartilages (cartilages of Wrisberg) are split off from the two pieces of the epi- 
 glottic, and are of the elastic type. 
 
 Attempts have been made to determine which branchial arches are represented by the 
 laryngeal cartilages. It seems quite definitely settled that the thyreoid is derived in part, at 
 least, from the fourth arch. There is much doubt as regards the others, for there is great 
 difficulty in determining their derivation in the human embryo, since the arches disappear 
 at such an early stage. Furthermore, some of these cartilages may represent arches which 
 are present in lower forms but do not appear in the higher Mammals. 
 
 The larynx is situated much farther cranially in the foetus and in the new- 
 born child than in the adult. In a five months foetus it extends into the naso- 
 pharyngeal cavity, whence it migrates caudally to its adult position. The 
 laryngeal skeleton becomes ossified during postnatal life. Ossification begins 
 in the thyreoid and cricoid cartilages at the age of eighteen to twenty years, 
 and in the arytenoids a few years later. Three centers appear in the thyreoid 
 one on each side near the inferior cornu and one in the medial line between 
 the two wings. In the cricoid, ossification begins near the upper border on 
 each side, in the arytenoids at the lower borders. Ossification usually begins 
 earlier and proceeds more rapidly in the male than in the female. 
 
 As an example of the explanation which Embryology offers of certain peculiarities of 
 structure in the adult, the case of the recurrent laryngeal nerve may be cited. The heart and 
 aortic arches are primarily situated in the cervical region. At that time a branch of the 
 vagus on each side, passes behind the fourth aortic arch to reach the larynx. As the 
 heart and arches recede into the thorax, the nerve is pulled caudally between its origin and 
 termination, so that in the adult the left nerve bends around the arch of the aorta and the 
 right around the subclavian artery. 
 
 The Trachea. 
 
 The portion of the original tube between the larynx and the two caudal out- 
 growths which form the bronchi and lungs, develops into the trachea. It lies 
 ventral to the oesophagus and is surrounded by mesodermal tissue which is 
 
364 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 destined to give rise to the connective tissue, includng the cartilage, of the adult 
 trachea (Figs. 284 and 320). The development of the tracheal rings is very 
 similar to that of the laryngeal cartilages. During the eighth or ninth week con- 
 densations appear in the mesenchyme, which are later transformed into hyalin 
 cartilage. The rings are not complete but remain open on the dorsal side. At 
 birth the trachea is collapsed, the ventral side being concave and the dorsal ends 
 of each ring being in contact. After respiration begins it is dilated and becomes 
 more or less rigid. Ossification of the tracheal rings begins in the male at the 
 age of about forty years, in the female at about sixty. The glands of the 
 trachea represent e vagina tions from the epithelial linings. 
 
 The Lungs. 
 
 As has been stated (p. 360), the caudal end of the original tube evaginates 
 to form two hollow buds which are the beginnings of the two lungs (Fig. 324). 
 The evagination takes place soon after or even along with the separation of the 
 lung groove from the gut. The right bud soon gives rise to three secondary 
 
 Aorta 
 
 Upper limb bud 
 
 (Esophagus 
 
 Body cavity 
 Pericardial cavity 
 
 FIG. 324. Transverse section of a 14 mm. pig embryo, at the level of the upper limb buds, 
 showing especially the two bronchi. 
 
 buds, the forerunners of the three lobes of the right lung. The left bud gives 
 rise to two secondary buds, the forerunners of the two lobes of the left lung 
 (Fig. 325). The primary buds may be said to represent the two bronchi arising 
 from the trachea, the five secondary buds to represent the bronchial rami 
 which extend into the five lobes of the lungs. Successive evaginations from 
 each of the five buds take place and form an extensive arborization for each 
 lobe (Figs. 326 and 327). 
 
THE DEVELOPMENT OF THE RESPIRATORY SYSTEM. 
 
 365 
 
 The manner in which the bronchial rami branch is not definitely known. 
 Some maintain that the branching is dichotomous, that is, each bud gives rise 
 to two equal buds and each of these to two others, and so on. In order to as- 
 sume the adult form, however, one of the buds places itself in line with the 
 preceding bud or bronchus while the other places itself as a lateral outgrowth. 
 Others hold that the growth is monopodial, that is, that the original bud grows 
 in a more or less direct line and the others develop as lateral outgrowths. When 
 
 Upper right lobe 
 Middle right lobe 
 
 Trachea 
 Upper left lobe 
 
 Mesoderm 
 (mesenchyme) 
 
 Lower right lobe 
 
 FIG. 325. Anlage of lungs of a human embryo of 4.3 mm. 
 
 His. 
 
 the evaginations that produce the bronchial rami are completed, each terminal 
 (respiratory) bronchus subdivides into three to six narrow tubules, the alveolar 
 ducts. The latter again branch into several wider compartments, the atria, 
 from which several air sacs are given off. The walls of the air sacs are evagi- 
 nated to form many closely set air cells which represent the ultimate branches 
 of the air passages of the lungs. 
 
 Trachea 
 
 Right bronchus 
 
 Left bronchus 
 
 Bronchial ramus 
 
 Mesoderm 
 (mesenchyme) 
 Bronchial ramus' 
 
 FIG. 326. Anlage of lungs of a human embryo of 8.5 mm. His. 
 
 While there is a general tendency toward bilateral symmetry in the various 
 sets of bronchial rami, the lobes of the lungs are asymmetrical. This asym- 
 metry is indicated in the five secondary buds that arise from the two primary, 
 since three arise on the right side and only two on the left. The three on the 
 right represent the upper, middle and lower lobes of the right lung (Fig. 325). 
 The upper is known as the eparterial from the fact that its bronchus lies dorsal 
 
366 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 to the pulmonary artery. No lobe develops on the left side corresponding to 
 the upper (eparterial) on the right. There is a possibility that it is absent in 
 order to allow the arch of the aorta to migrate caudally as it normally does 
 (see p. 254). One of the larger ventral bronchial rami of the left lung is ab- 
 sent, owing to the inclination of the heart toward the left side; but as a compensa- 
 tion the corresponding ramus of the right lung develops more extensively 
 and projects into the space between the pericardium and diaphragm as the 
 infracardiac ramus. 
 
 From the fact that the anlage of the respiratory system is enclosed within 
 the mesentery between the gut and the pericardial cavity, and that its caudal end 
 becomes enclosed within the dorsal edge of the septum transversum, it is obvious 
 
 Pulmonary artery 
 
 Right bronchu 
 
 Upper right 
 bronch. ramus 
 
 Middle right 
 bronch. ramus 
 
 Lower right 
 bronch. ramus 
 
 Mesoderm 
 (mesenchyme) 
 
 Trachea 
 
 Left bronchus 
 
 Upper left 
 bronch. ramus 
 
 Lower left branch 
 pulmonary vein 
 
 Lower left 
 bronch. ramus 
 
 FIG. 327. Anlage of lungs of a human embryo of 10.5 mm. His, 
 
 that the lungs will push their way into the dorsal parietal recesses or pleural 
 cavities (Figs. 328 and 333). The way in which the lungs and pleural cavities 
 enlarge and separate the pericardium from the body wall on each side and from 
 the diaphragm is described on page 376 (see Figs. 334 and 335). The mesoder- 
 mal tissue that surrounds the primary lung buds is in part pushed before the 
 numerous outgrowths and in part remains among them (Figs. 325, 326, 327). 
 The part around the lungs, with its covering of mesothelium, comes to form the 
 visceral layer of the pleura which closely invests the entire surface of the lungs 
 and dips down between the lobes. At the roots of the lungs it is continuous 
 with the parietal layer of the pleura lining the inner surface of the pleural cavi- 
 ties. The mesodermal tissue among the bronchi and their terminations gives 
 rise to the connective tissue that separates the lobes and lobules and invests all 
 the structures in the interior of the lungs. This connective tissue at first con- 
 
THE DEVELOPMENT OF THE RESPIRATORY SYSTEM. 
 
 367 
 
 stitutes a large part of the lungs, but as development proceeds, the more 
 rapid growth of the respiratory parts results in the relatively small amount of 
 connective tissue characteristic of the adult lung. 
 
 Changes in the Lungs at Birth. At birth the lungs undergo rapid and 
 remarkable changes in consequence of their assuming the respiratory function. 
 These changes affect their size, form, position, texture, weight, etc., and 
 furnish probably the only certain means of distinguishing between a still-born 
 child and one that has breathed. In the foetus at term the lungs are small, 
 possess rather sharp margins and lie in the dorsal part of the pleural cavities. 
 
 Diaphragm 
 
 Lungs 
 
 Pleural ca vities 
 
 FIG. 328. Transverse section of a pig embryo of 35 mm., showing the developing lungs (bronchial 
 rami surrounded by mesoderm). The oesophagus is seen between the two lungs; above the 
 oesophagus is the aorta. The dark mass in the lower part of the figure is the liver. 
 Photograph. 
 
 After respiration they enlarge, fill practically the entire pleural cavities and 
 naturally become more rounded at their margins. The introduction of air into 
 the air passages converts the compact, gland-like, fcetal lung into a loose, 
 spongy tissue. The specific gravity is changed from 1.056 to 0.342. While 
 there is a gradual increase in the weight of the lungs during development, there 
 is a very sudden increase at birth when the blood is freely admitted to them 
 through the pulmonary arteries. The weight of the lungs relative to that of 
 the body changes from about i to 70 before birth, to about i to 35 or 40 after 
 birth. 
 
368 TEXT-BOOK OF EMBRYOLOGY. 
 
 Anomalies. 
 
 THE LARYNX. The larynx may be excessively large or unusually small. 
 Occasionally the epiglottic cartilage consists of two pieces, indicating a failure 
 of the two anlagen to fuse (p. 362). Similar defects may occur in the other 
 cartilages that are derived from more than one anlage. The ventricle on either 
 side may be abnormally large with an exaggerated appendage (laryngeal 
 pouch) . This condition resembles that in the anthropoid apes. 
 
 THE TRACHEA. The trachea is sometimes absent, in which case the bronchi 
 arise immediately below the larynx, indicating a failure on the part of the 
 original tube to elongate. The trachea may be abnormally short. Rarely 
 there is a direct communication between the trachea and oesophagus, probably 
 due to an incomplete separation of the lung groove from the gut (p. 360). The 
 cartilaginous rings may vary in number as a result of abnormal splittings and 
 fusions. 
 
 THE LUNGS. Rarely the eparterial bronchial ramus on the right side 
 arises as a branch of the trachea and not as a branch of the bronchus (p. 365). 
 This condition is normal in certain Mammals (ox, sheep) . Rarely an eparterial 
 bronchial ramus is present on the left side, thus producing a third lobe for 
 the left lung. In some animals an eparterial ramus is normally present on 
 each side, the larger bronchial rami thus being bilaterally symmetrical. Varia- 
 tion in size and number of lobes is not infrequent. Supernumerary or acces- 
 sory lobes, formed either by evaginations from the original anlage or by in- 
 dependent evaginations from the gut, are met with in rare cases. 
 
 Occasionally some portion of either lung is defective. The bronchial bud 
 that would normally give rise to the lung tissue in that region fails to develop 
 properly, and the result is a number of rami, without the ultimate terminations, 
 surrounded by vascular tissue. The rami may remain normal or may become 
 dilated and form large bronchial cysts. 
 
 References for Further Study. 
 
 BONNET, R.: Lehrbuch der Entwickelungsgeschichte. Berlin, 1907. 
 
 FLINT, J. M.: The Development of the Lungs. American Jour, of Anat., Vol. VI, 1906. 
 
 GOPPERT, E.: Die Entwickelung des Mundes und der Mundhohle mit Driisen irtid 
 Zunge; die Entwickelung der Schwimmblase, der Lunge und des Kehlkopfes der Wirbeltiere. 
 In Hertwig's Handbuch der vergleich. u. experiment. Entivickelungslehre der Wirbeltiere, 
 Bd. II, Teil I, 1902. 
 
 HERTWIG, O.: Lehrbuch der Entwickelungsgeschichte des Menschen und der Wirbel- 
 tiere. Jena, 1906. 
 
 His, W.: Zur Bildungsgeschichte der Lungen beim menschlichen Embryo. Arch. /. 
 Anat. u. Physiol., Anat. Abth., 1887. 
 
 KALLIUS, E.: Beitrage zur Entwickelungsgeschichte des Kehlkopfes. Anat. Hejte, 
 Bd. IX, 1897. 
 
 KOLLMANN, J.: Lehrbuch der Entwickelungsgeschichte des Menschen. Jena, 1898. 
 
 KOLLMANN, J.: Handatlas der Entwickelungsgeschichte des Menschen. Jena, 1907. 
 
THE DEVELOPMENT OF THE RESPIRATORY SYSTEM. 369 
 
 McMuRRiCH, J. P.: The Development of the Human Body. Third Ed., 1907. 
 
 PIERSOL, G. A.: Teratology. In Wood's Reference Handbook of the Medical Sciences, 
 Vol. VII, 1904. 
 
 SYMINGTON, J.: On the Relations of Larynx and Trachea to the Vertebral Column in 
 the Foetus and Child. Journ. of Anat. and PhysioL, Vol. IX. 
 
CHAPTER XIV. 
 
 THE DEVELOPMENT OF THE CGELOM (PERICARDIAL 
 
 PLEURAL AND PERITONEAL CAVITIES), THE 
 
 PERICARDIUM, PLEUROPERITONEUM, 
 
 DIAPHRAGM, AND MESENTERIES. 
 
 In the Chapter on the development of the germ layers, it is stated that the 
 peripheral part of the mesoderm splits into two layers, an outer or parietal, and 
 an inner or visceral (Fig. 81; see also p. 83). The parietal layer of mesoderm 
 and the ectoderm constitute the somatopleure. The visceral layer and the 
 entcderm constitute the splanchnopleure (Fig. 81). The cleft or cavity 
 that appears between the parietal and visceral layers is the ccelom or body 
 cavity and is lined with a layer of flattened mesodermal cells known as the 
 mesothelium. It will be remembered that in the earlier stages of development a 
 portion of the embryonic disk becomes constricted off from the yolk sac to form 
 the simple cylindrical body (p. 137). Along each side of the axial portion of the 
 germ disk, and also at its cephalic and caudal ends, the germ layers bend ven- 
 trally and then medially until they meet and fuse in the midventral line (p. 141). 
 In this way a part of the somatopleure forms the lateral and ventral portions of 
 the body wall (Fig. 141). At the same time the axial portion of the entoderm is 
 bent into a tube which is closed at both ends the primitive gut and is then 
 pinched off from the rest of the entoderm except at one point, where the cavity 
 of the gut remains in communication with the cavity of the yolk sac. The 
 splanchnic mesoderm adjacent to the entoderm on each side comes in contact 
 and fuses with the corresponding portion from the opposite side, thus forming 
 a sheet of tissue which encloses the primitive gut and also forms a partition be- 
 tween the two parts of the coelom. This sheet of tissue is the common mesentery 
 and is attached to the dorsal and ventral body walls along the medial line. 
 The portion between the gut and the dorsal body wall is the dorsal mesentery, 
 the portion between the gut and the ventral body wall is the ventral mesentery. 
 Thus the gut is suspended in the common mesentery (Figs. 235 and 320). 
 
 When portions of the somatopleure and splanchnopleure are bent ventrally 
 the coelom between the portions is naturally carried with them. This part of 
 the coelom thus becomes enclosed within the cylindrical body and constitutes 
 the intraembryonic or simply the embryonic coelom (body cavity proper). The 
 part of the coelom which, while the germ layers were still flat, was situated more 
 peripherally constitutes the extraembryonic coelom or eococcelom (extraembryonic 
 
 370 
 
PERICARDIUM, PLEUROPERITOXEUM, DIAPHRAGM AND MESENTERIES. 371 
 
 body cavity). From the nature of the bending process, the embryonic ccelom 
 is divided into bilaterally symmetrical parts by the common mesentery (Fig. 
 235). These two simple cavities are the forerunners of all the serous cavities of 
 the body. The various partitions between the serous cavities, the walls of the 
 cavities and the mesenteries proper are all derived from the somatic and 
 splanchnic mesoderm with its covering of mesothelium. 
 
 While the foregoing would represent a typical case of early ccelom and 
 mesentery formation, there are certain modifications and peculiarities in the 
 higher Mammals and in man. In all cases the splitting of the mesoderm to 
 form the ccelom proceeds from the periphery of the germ disk toward the axial 
 portion (p. 85). In the human embryo the bending ventrally and fusing of the 
 germ layers to form the cylindrical body begins in the anterior region of the 
 disk and is accomplished there before the splitting of the mesoderm is com- 
 pleted. The peripheral splitting has resulted in the formation of the exoccelom, 
 but at the time when the ventral fusion of the germ layers takes place, the split- 
 ting has not extended axially to a sufficient degree to form the intraembryonic 
 coelom. The latter, which appears later in this region, never communicates 
 laterally, therefore, with the exoccelom. Caudal to this region the ccelom is 
 formed as in the typical case. The more anterior part of the ccelom on each 
 side is thus primarily a pocket-like cavity. It communicates with the rest of the 
 coelom at about the level of the yolk stalk. In the region of the fore-gut, the 
 future cesophagus, no distinct mesentery is formed, but the fore-gut remains 
 broadly attached to the dorsal body wall. A ventral mesentery is lacking from 
 a point just cranial -to the yolk stalk to the caudal end of the gut. There are 
 no coelomic cavities in the branchial arches, the ccelom extending only to the 
 last branchial groove. 
 
 In very young human embryos the primitive segments contain small cavities. 
 These cavities soon disappear, being filled with cells from the surrounding 
 parts of the segments. Whether they represent isolated portions of the ccelom 
 is not certain. In the lower Vertebrates, the cavities of the primitive segments 
 regularly communicate with the ccelom, and in the sheep the cavities of the first 
 formed segments are continuous with the ccelom. In the head there is no 
 cavity analogous to the ccelom in the body. In but one human embryo have 
 any cavities in the head resembling those of the primitive segments been 
 observed (see p. 301). 
 
 The Pericardial Cavity, Pleural Cavities and Diaphragm. 
 
 The pericardial and pleural cavities and diaphragm are so closely related in 
 their development that they must be considered together. In the region just 
 caudal to the visceral arches, where the two anlagen of the heart appear, the 
 embryonic coelom becomes dilated at a very early stage to form the primitive 
 pericardial cavity (parietal cavity of His). After the two anlagen of the heart 
 
372 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 unite to form a simple tubular structure (p. 227; also Fig. 194), the latter is 
 suspended in the cavity by a mesentery which consists of a dorsal and a ventral 
 part, a dorsal and a ventral mesocardium. By these the cavity is at first divided 
 into two bilaterally symmetrically parts. The mesocardia soon disappear and 
 leave the heart attached only to the large vascular trunks which suspend it 
 in the single pericardial cavity. The early pericardial cavity is simply the 
 cephalic end of the embryonic ccelom and is therefore directly continuous with 
 the rest of the ccelom. As mentioned on p. 371 it does not, however, at any 
 time communicate laterally with the extraembryonic coelom. 
 
 The communication between the pericardial cavity and the rest of the em- 
 bryonic coelom is soon partly cut off by the development of a transverse fold 
 the septum transversum. This septum is formed in close relation with the 
 omphalomesenteric veins. These vessels unite in the sinus venosus at the 
 caudal end of the heart, whence they diverge in the splanchnic mesoderm. 
 
 am 
 
 vom 
 
 rpr 
 
 FIG. 329. Transverse sections of a rabbit embryo, showing how the omphalomesenteric veins (vom) 
 push outward across the ccelom and fuse with the lateral body wall, forming the ductus 
 pleuro-pericardiacus (rp } rpd) ; am, amnion. Ravn. 
 
 They are thus embedded in the mesodermal layer of the splanchnopleure, and as 
 the latter closes in from either side to form the gut, the vessels form ridge-like 
 projections into the ccelom. As the vessels increase in size, the ridges become 
 so large that the splanchnic mesoderm is pushed outward against the parietal 
 mesoderm and fuses with it (Fig. 329). Thus a partition is formed on each side, 
 which is attached on the one hand to the mesentery and on the other hand to the 
 ventral and lateral body walls, and which contains the omphalomesenteric veins. 
 It is obvious that these partitions, forming the septum transversum, close the 
 ventral part of the communication between the pericardial cavity and the rest of 
 the coelom. The dorsal part of the communication remains open on each side 
 of the mesentery as the ductus pleuro-pericardiacus (dorsal parietal recess of His) 
 (Figs. 329 and 330). 
 
 As the heart develops it migrates caudally, and by corresponding migration 
 the pericardial cavity draws the ventral edge of the septum transversum farther 
 caudally, so that the cephalic surface of the latter faces ventrally and cranially. 
 
PERICARDIUM, PLEUROPERITONEUM, DIAPHRAGM AND MESENTERIES. 373 
 
 In other words the septum comes to lie in an oblique cranio-caudal plane. The 
 pericardial cavity therefore comes to lie ventral to the ductus pleuro-pericardiaci. 
 The latter one on each side of the mesentery are two passages which com- 
 
 Pericardial cavity 
 
 Lateral mesocardium \ 
 
 Pericardium 
 
 Septum transversum 
 
 Liver 
 
 Ductus choledochus 
 
 Yolk stalk - 
 
 Ventral aortic trunk 
 Dorsal mesocardium 
 
 Sinus venosus 
 Duct of Cuvier 
 
 Left umbilical vein 
 Left omphalomes. vein 
 Ductus pleuro-pericardiacus 
 
 tomach 
 Peritoneal cavity 
 
 Pharynx s. R 
 
 Dorsal mesocardium \ /, "c-w 
 
 } C 
 
 
 Ductus pleuro- 
 pericardiacus 
 
 FIG. 330. From a model of the septum transversum, liver, etc., of a human embryo 
 of 3 mm. His, K oilman. 
 
 municate on the one hand with the pericardial cavity and on the other hand with 
 the peritoneal cavity ,- while they themselves form the cavities into which the lungs 
 grow the pleural cavities. (Compare Figs. 330, 331 and 332.) 
 
 Aorta 
 
 Ductus pleuro- 
 pericardiacus 
 Duct of Cuvier 
 
 Heart 
 
 s> ^-- ^ Pericardial cavity 
 
 FIG. 331. View (in perspective) of the pcricardial cavity and ductus pleuro-pericardiaci 
 of a rabbit embryo of 9 days. Ravn. 
 
 The pleural cavities also become separated from the pericardial cavity, ap- 
 parently through the agency of the ducts of Cuvier. The anterior and posterior 
 cardinal veins on each side unite to form the duct of Cuvier which then extends 
 
374 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 from the body wall through the dorsal free edge of the septum transversum to 
 join the sinus venosus (Fig. 330). This free edge is pushed farther and 
 farther into the ductus pleuro-pericardiacus (Fig. 331) until it meets and fuses 
 
 Pleural cavity 
 
 \ 
 
 \ Dorsal mesentery 
 
 ^fj:, 
 
 C" 
 
 Lateral mesocardium 
 
 Pericardial cavity 
 
 ___ Lateral mesocardium 
 
 Dorsal mesocardium 
 Heart 
 
 FIG. 332. View (in perspective) of the pericardia! and plcural cavities of a human embryo 
 
 of 7.5 mm. Kollmann. 
 
 The arrow points through the opening which forms the communication between the pleural 
 and peritoneal cavities, and which is eventually closed by the pleuro-peritoneal membrane. 
 
 with the mesentery or posterior mediastinum. This process thus produces a 
 septum between each pleural cavity and the pericardial cavity. 
 
 The septum transversum early acquires still more complicated relations 
 
 Lung 
 
 Pleuro-peritoneal membrane 
 
 Mesentery of i __, 
 
 inf. vena cava i " 
 
 Inferior vena cava 
 
 Mesonephros -V jig 
 
 Lung 
 
 ii Pleuro-peritoneal membrane 
 ^Mesentery 
 
 1 
 
 "^ P 1 euro-peritoneal membrane 
 - 1 CEsophagus 
 
 -.' Dorsal mesogastrium 
 
 FIG. 333. Ventral view (in perspective) of parts of the lungs, pleural cavities, peritoneal cavity, 
 and the pleuro-peritoneal membranes in a rat embryo. Ravn. 
 
 from the fact that the liver grows into its caudal part (Fig. 330) . It may, for this 
 reason, be divided into a caudal part in which the liver is situated and which 
 furnishes the fibrous capsule (of Glisson) and the connective tissue of the liver, 
 and a cephalic part which may be called the primary diaphragm. These two 
 parts at first are not separate, the separation taking place secondarily. After 
 
PERICARDIUM, PLEUROPERITOXEUM, DIAPHRAGM AND MESENTERIES. 375 
 
 the separation between the pericardial cavity and the pleural cavities, the latter 
 for a time remain in open communication with the rest of the ccelom or peritoneal 
 cavity. The lungs, as they develop, grow into the pleural cavities (Fig. 332) 
 until their tips finally touch the cephalic surface of the liver. At this point 
 folds grow from the lateral and dorsal body walls (Fig. 333) and unite ventrally 
 with the primary diaphragm and medially with the mesentery. These folds 
 the pleuroperitoneal membranes separate the pleural cavities from the perit- 
 oneal cavity and complete the diaphragm. Thus the diaphragm, from the stand- 
 
 a- PL cav. 
 
 p.m. 
 
 PC. cav. 
 
 Lv.c. 
 
 FIG. 335. 
 
 FIG. 334. Transverse section through the thoracic region of a rabbit embryo of 15 days. Hochstetter. 
 FIG. 335. Transverse section through the thoracic region of a cat embryo of 25 mm. Hochstetter. 
 I.v.c.. Inferior vena cava; Inf.-c. 1., infracardiac lobe of lung; L. t lung; Oe.. oesophagus; PC. cav., 
 
 pericardial cavity; PI. cav., pleural cavity; Pl.-p. m., pleuro- pericardial membrane; Pu.-h. r. t 
 
 pulmo-hepatic recess. 
 
 point of development, consists of two parts : a ventral part which is the cephalic 
 portion of the original septum transversum, and a dorsal part which develops 
 later from the body wall and is the closing membrane between the peritoneal 
 and pleural cavities. The musculature of the diaphragm is considered in the 
 chapter on the muscular system (p. 300). 
 
 While the foregoing structures are being formed, decided changes take place 
 in their positions and relations. At first the heart lies far forward in the cervi- 
 cal region near the visceral arches. Later it migrates caudally and the pericardial 
 
376 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 cavity comes to occupy much of the ventral part of the thorax, the pericardium 
 having extensive attachments to the ventral body wall and to the cephalic sur- 
 face of the primary diaphragm (Fig. 330). The diaphragm is much farther 
 forward than in the adult and is broadly attached to the cephalic surface of the 
 liver. The principal changes which bring about the adult conditions are the 
 growth of the lungs, the separation of the diaphragm from the liver, and the 
 
 caudal migration of the diaphragm itself. With 
 the development of the lungs, the pleural cavities 
 necessarily enlarge and push their way ventrally. 
 In so doing they split the pericardium away from 
 the lateral body walls and likewise from the dia- 
 phragm (compare Figs. 334 and 335). Thus the 
 pericardial cavity comes to be confined more and 
 more closely to the medial ventral position. The 
 separation of the liver from the primary diaphragm 
 is caused by changes in the peritoneum which at 
 first covers the caudal, lateral and ventral surfaces 
 of the liver. The cephalic surface of the liver, as 
 stated above, is covered by the primary diaphragm 
 itself. The peritoneum is reflected from the surface 
 of the liver on to the diaphragm, and at the line of 
 reflection a groove appears on each side, extending 
 from the midventral line around as far as the 
 attachment of the liver to the diaphragm. The 
 FIG. 336. Diagram showing the grooves gradually grow deeper, the peritoneum 
 human^e^br^^^F^lerent pushing its way, as a flat sac, between the two 
 stages. Mall. structures, until the separation is almost complete. 
 
 The positions are those shown . 
 
 in embryos of Mall's collection There is left, however, an area of attachment 
 (except KO, which is a 10.2 between the liver and diaphragm, over which the 
 
 mm. embryo of the His collec- m f r 
 
 tion) ; xii being an embryo of peritoneum is reflected, the ligamenlum coronarium 
 
 In the medial line there is also left a 
 
 ix, of 17 mm.; XLin, of 15 broad thin lamella which is attached to the dia- 
 
 mm.; VI, of 24 mm. The 
 
 numerals on the right indicate phragm, the liver and the ventral body wall. This 
 
 is a remnant of the ventral mesentery and forms 
 
 the ligamenlum suspensorium (falciforme) hepatis. In its free caudal edge 
 is embedded the ligamentum teres hepatis which is closely related to the 
 umbilical vein (see p. 261). The diaphragm itself, during its development, 
 migrates from a position in the cervical region, where the septum transversum 
 first appears, to its final position opposite the last thoracic vertebrae. During 
 the migration the plane of direction also changes several times, as may be 
 seen in Fig. 336. 
 
PERICARDIUM, PLEUROPERITONEUM, DIAPHRAGM AND MESENTERIES. 377 
 
 The Pericardium and Pleura. Since the pericardial cavity represents a 
 portion of the original ccelom, the lining of the cavity must be a derivative of 
 either the parietal or the visceral layer of mesoderm or of both. The common 
 mesentery in which the heart develops is derived from the visceral layer. Con- 
 sequently the epicardium is a derivative of the visceral mesoderm (Fig. 203). 
 The pericardium is derived from three regions of mesoderm. The greater 
 part is derived from the parietal mesoderm, since the body wall which is com- 
 posed of parietal mesoderm is also primarily the wall of the pericardial cavity. 
 A small dorsal portion is probably derived from the mesoderm at the root of the 
 dorsal mesocardium (Fig. 203). The septum transversum primarily forms 
 the caudal wah 1 of the pericardial cavity, and, since the septum is a derivative 
 of the visceral layer, the caudal wall is derived from this layer. The three 
 portions are, of course, continuous. 
 
 The lungs first appear in the common mesentery as an evagination from the 
 primitive gut (Fig. 320, p. 360). As they develop further they grow into the 
 pleural cavities, pushing a part of the mesentery before them. This part of 
 the mesentery thus invests the lungs and forms the visceral layer of the pleura 
 which is therefore a derivative of the visceral mesoderm. The parietal layer of 
 the pleura is a derivative of the parietal mesoderm, since the wall of the pleural 
 cavity is primarily the body wall. 
 
 The lining of all these cavities is at first composed of mesothelium and 
 mesenchyme. The latter is transformed into the delicate connective tissue of 
 the serous membranes, and the mesothelium becomes the mesothelium of 
 the membranes. 
 
 The Omentum and Mesentery. 
 
 From the septum transversum (or diaphragm) to the anus the gut is sus- 
 pended in the ccelom (or abdominal cavity) by means of the dorsal mesentery. 
 This is attached to the dorsal body wall along the medial line and lies in the 
 medial sagittal plane (Fig. 301; compare with Fig. 235). On the ventral side of 
 the gut a mesentery is lacking from the anus to a point just cranial to the yolk 
 stalk (p. 371). There is, however, a small ventral mesentery extending a short 
 distance caudally from the septum transversum. On account of its relation to 
 the stomach this is known as the ventral mesogastrium (Fig. 301). These two 
 sheets of tissue, the dorsal and ventral mesenteries, are destined to give rise to 
 the omenta and mesenteries of the adult. Owing to the enormous elongation of 
 the gut and its extensive coiling in the abdominal cavity, the primary mesen- 
 teries are twisted and thrown into many folds which enclose certain pockets or 
 bursas. Furthermore, certain parts of the gut which are originally free and 
 movable become attached to other parts and to the body walls through fusions 
 of certain parts of the mesentery with one another and with the body walls. 
 
378 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 The Greater Omentum and Omental Bursa. A small part of the gut 
 caudal to the diaphragm is destined to become the stomach, and the portion of 
 the mesentery which attaches it to the dorsal body wall is known as the dorsal 
 mesogastrium (Fig. 301). The latter is inserted along the greater curvature of 
 the stomach and lies in the medial sagittal plane so long as the stomach lies in 
 this plane. When the stomach turns so that its long axis lies in a transverse 
 direction and its greater curvature is directed caudally (p. 336), the dorsal 
 mesogastrium changes its position accordingly. From its attachment along the 
 dorsal body wall it bends to the left and then ventrally to its attachment along 
 the greater curvature of the stomach. Thus a sort of sac is formed dorsal to 
 the stomach (Figs. 337 and 338). This sac is really a part of the abdominal or 
 
 Yolk stalk 
 
 Stomach 
 
 Rectum 
 
 Duodenum 
 
 Caecum 
 Appendix 
 Mesentery 
 
 Yolk stalk 
 
 FIG. 337. 
 
 Stomach 
 
 Rectum 
 
 FIG. 338. 
 
 FIG. 337. Diagram of the gastrointestinal tract and its mesenteries 
 
 at an early stage. Ventral view. Hertwig. 
 FIG. 338. Same at a later stage Hertwig. 
 The arrow points into the bursa omentalis. 
 
 peritoneal cavity and opens toward the right side. The ventral wall is formed 
 by the stomach, the dorsal and caudal walls by the mesogastrium. The cavity 
 of the sac is the omental bursa (bursa omentalis) ; the mesogastrium forms the 
 greater amentum (omentum majus) . The opening from the bursa into the general 
 peritoneal cavity is the epiploic foramen (foramen of Winslow). (Fig. 314.) 
 
 From the third month on, the greater omentum becomes larger and gradually 
 extends toward the ventral abdominal wall, over the transverse colon, and then 
 caudally between the body wall and the small intestine (Figs. 339 and 340). 
 The portion between the body wall and intestine encloses merely a flat cavity 
 continuous with the larger cavity dorsal to the stomach. From the fourth 
 month on, the omentum fuses with certain other structures and becomes less 
 free. The dorsal lamella fuses with the dorsal body wall on the left side and 
 
PERICARDIUM, PLEUROPERITONEUM, DIAPHRAGM AND MESENTERIES. 379 
 
 with the transverse mesocolon and transverse colon (Fig. 341). During the 
 first or second year after birth the two lamellae fuse with each other caudal 
 to the transverse colon to form the greater omentum of adult anatomy. 
 
 Diaphragm . 
 
 Lesser omentum 
 
 Pancreas 
 Bursa omentalis 
 
 Stomach 
 
 Greater omentum 
 
 Duodenum 
 
 Transverse mesocolon 
 
 Transverse colon 
 
 Mesentery of 
 small intestine 
 
 Small intestine ----- V\~ 
 
 FIG. 339. 
 
 Diaph. 
 
 FIG. 340. FIG. 341. 
 
 FIGS. 339, 340 and 341. Diagrams showing stages in the development of the bursa omentalis, the 
 greater omentum, and the fusion of the latter with the transverse mesocolon. Diagrams 
 represent sagittal sections. For explanation of lettering in Figs. 340 and 341 see Fig. 339. 
 
 The Lesser Omentum. It has already been noted that the liver grows into 
 the caudal portion of the septum transversum (p. 374). Since the ventral 
 mesentery in the abdominal region, or the ventral mesogastrium, is primarily 
 
380 TEXT-BOOK OF EMBRYOLOGY. 
 
 directly continuous with the septum transversum, it is later attached to the 
 liver. In other words it passes between the liver and the lesser curvature of the 
 stomach and also extends along the duodenal portion of the gut for a short 
 distance (Fig. 301). As the stomach turns to the left the ventral mesentery is 
 also drawn toward the left and comes to lie almost at right angles to the sagittal 
 plane of the body, forming the lesser omentum (omentum minus) or the hepato- 
 gastric and hepatoduodenal ligaments of the adult (Figs. 341 and 342). 
 
 The Mesenteries. So long as the intestine is a straight tube, the dorsal 
 mesentery lies in the medial sagittal plane, its dorsal attachment being practi- 
 cally of the same length as its ventral (intestinal) attachment. As development 
 proceeds, the intestine elongates much more rapidly than the abdominal walls, 
 and the intestinal attachment of the mesentery elongates accordingly. When 
 the portion of the intestine to which the yolk stalk is attached grows out into the 
 proximal end of the umbilical cord (p. 338), the corresponding portion of the 
 mesentery is drawn out with it (Fig. 301). When the intestine returns to the 
 abdominal cavity and forms the primary loop, with the caecum to the right side 
 (p. 339), its mesenteric attachment is carried out of the medial sagittal plane. 
 This results in a funnel-shaped twisting of the mesentery (Figs. 337 and 338). 
 The portion of the mesentery which forms the funnel is destined to become the 
 mesentery of the jejunum, ileum, and ascending and transverse colon, and is 
 attached to the dorsal body wall at the apex of the funnel (Fig. 337, 338, 342). 
 This condition is reached about the middle of the fourth month. 
 
 Up to this time the mesentery and intestine are freely movable, that is, they 
 have formed no secondary attachments. From this time on, as the intestine 
 continues to elongate and forms loops and coils, the mesentery is thrown into 
 folds, and certain parts of it fuse with other parts and with the body wall. 
 Thus certain parts of the intestine become less free or less movable within the 
 abdominal cavity. 
 
 The duodenum changes from the original longitudinal position to a more 
 nearly transverse position and, with its mesentery the mesoduodenum fuses 
 with the dorsal body wall, thus becoming firmly fixed. Since the mesoduode- 
 num fuses with the body wall, the duodenum has no mesentery in the adult. 
 The pancreas, which is primarily enclosed within the mesoduodenum, also 
 becomes firmly attached to the dorsal body wall (compare Figs. 339 and 340). 
 
 The mesentery of the transverse colon, or the transverse mesocolon, which 
 lies across the body ventral to the duodenum (Figs. 338 and 342), fuses with the 
 ventral surface of the latter and with the peritoneum of the dorsal body wall. 
 In this way the dorsal attachment of the transverse mesocolon is changed from 
 its original sagittal direction to a transverse direction (Figs. 340 and 341). The 
 mesocolon itself forms a transverse partition which divides the peritoneal cavity 
 into two parts, an upper (or cranial) which contains the stomach and liver, and 
 
PERICARDIUM, PLEUROPERITONEUM, DIAPHRAGM AND MESENTERIES. 381 
 
 a lower (or caudal) which contains the rest of the digestive tube except the 
 duodenum. The mesentery of the duodenum and pancreas changes from a 
 serous membrane into subserous connective tissue, and these two organs as- 
 sume the retroperitoneal position characteristic of the adult (Fig. 339). 
 
 The mesentery of the descending colon, or the descending mesocolon, lies in 
 the left side of the abdominal cavity, in contact with the peritoneum of the body 
 wall (see Fig. 342). It usually fuses with the peritoneum, and the descending 
 
 Dors, mesogastrium 
 
 Lesser omentum 
 (hep.-gast. Kg.) 
 
 Bile duct 
 
 Mesoduodenum 
 
 Transv. colon 
 
 Spleen 
 
 Duo.-jej. flexure 
 
 Desc. colon 
 Desc. mesocolon 
 
 Appendix 
 
 Yolk stalk 
 
 Medial line 
 
 FIG. 342. Gastrointestinal tract and mesenteries in a human embryo. The arrow 
 points into the bursa omentalis. Kollmann. 
 
 colon thus becomes fixed. After the ascending colon is formed, the ascending 
 mesocolon usually fuses with the peritoneum on the right side (see Fig. 342). In 
 a large percentage (possibly 25 per cent.) of individuals, the fusion between the 
 peritoneum and the ascending and descending mesocolon is incomplete or 
 
 wanting. 
 
 The sigmoid mesocolon bends to the left to reach the sigmoid colon, but 
 forms no secondary attachments. It is continuous with the mesorectum which 
 maintains its original sagittal position. A sheet of tissue the mesoappendix 
 continuous with and resembling the mesentery, is attached to the cascum and 
 vermiform appendix (Fig. 342). It probably represents a drawn out portion of 
 
382 TEXT-BOOK OF EMBRYOLOGY. 
 
 the original common mesentery, since the caecum and appendix together are 
 formed as an evagination from the primitive gut. 
 
 Normally the mesentery of the small intestine forms no secondary attach- 
 ments, but is thrown into a number of folds which correspond to the coils of the 
 intestine. 
 
 The secondary attachments of the greater omentum and the fusion of the 
 two lamellae have been described earlier in this chapter (p. 378). The mesen- 
 teries of the urogenital organs are considered in connection with the develop- 
 ment of those organs (Chapter XV). 
 
 The Peritoneum. The thin layer of tissue composed of delicate fibrous 
 connective tissue and mesothelium which lines the abdominal cavity and is re- 
 flected over the various omenta, mesenteries and visceral organs, is derived 
 wholly from the mesoderm. The lining of the coelom is composed of mesothe- 
 lium and mesenchyme. The latter gives rise to the connective tissue of the 
 serous membranes, and the mesothelial layer becomes the mesothelium of these 
 membranes. 
 
 Anomalies. 
 
 THE PERICARDIUM. Anomalous conditions of the pericardium are usually, 
 although not necessarily, associated with anomalies of the heart. They may 
 also be associated with defects in the diaphragm. Displacement of the heart 
 (ectopia cordis) is accompanied by displacement of the pericardium. The 
 heart sometimes protrudes through the thoracic wall, and, as a rule, in such cases 
 is covered by the protruding pericardium. In extensive cleft of the thoracic 
 wall (thoracoschisis, Chap. XIX) the pericardium may be ruptured. 
 
 THE DIAPHRAGM. The most common malformation of the diaphragm is a 
 defect in its dorsal part, occurring much more frequently on the left than on the 
 right side. The defect may affect but a small portion or may be extensive, the 
 peritoneum being directly continuous with the parietal layer of the pleura. 
 Such defects are due to the imperfect development of the pleuro-peritoneal mem- 
 brane which normally grows from the dorso-lateral part of the body wall and 
 fuses with the edge of the primary diaphragm, thus separating the pleural and 
 and peritoneal cavities (p. 375). The most conspicuous result of defects in the 
 dorsal part of the diaphragm is diaphragmatic hernia, in which parts of the 
 stomach, liver, spleen and intestine project into the pleural cavity, either free or 
 enclosed in a peritoneal sac. Defects in the ventral part of the diaphragm, due 
 to imperfect development of portions of the septum transversum, are not 
 common. 
 
 THE MESENTERIES AND OMENTA. Extensive malformations of the mesen- 
 teries apparently do not occur without extensive malformations of the digestive 
 tract. One of the most striking anomalous conditions is a retained embryonic 
 
PERICARDIUM, PLEUROPERITONEUM, DIAPHRAGM AND MESENTERIES. 333 
 
 simplicity of the mesentery, concurrent with corresponding simplicity in the 
 loops and coils of the intestine. In this anomaly the intestine has failed to 
 arrive at its usual complicated condition and the mesentery has not undergone 
 the usual processes of folding and fusion (p. 380 et seq.). Minor variations in 
 the mesenteries and omenta are probably due largely to imperfect fusion of 
 certain parts with one another and with the body wall. It is not uncommon to 
 find the ascending or descending colon, or both, more or less free and mov- 
 able. This condition is due to imperfect fusion of the mesocolon with the body 
 wall (p. 381). If the greater omentum is wholly or partially divided into sheets 
 of tissue, the two primary lamellae have failed to fuse completely (p. 379). 
 This divided condition is normal in many Mammals. 
 
 References for Further Study. 
 
 BRACKET, A.: Recherches sur le developpement du diaphragme et du foie. Jour, de 
 VAnat. et de la Physiol., T. XXXII, 1895. 
 
 BROMAX, J. : Die Entwickelungsgeschichte der Bursa omentalis und ahnlicher Recess- 
 bildungen bei den Wirbeltieren. Wiesbaden, 1904. 
 
 BROMAX, I.: Ueber die Entwickelung und Bedeutung der Mesenterien und der Korper- 
 hohlen bei den Wirbeltieren. Ergebnisse der Anat. u. Entwick., Bd. XV, 1906. 
 
 BROSSIKE, G.: Ueber intraabdominale (retroperitoneale) Hernien und Bauchfelltaschen, 
 nebst einer Darstellung der Entwickelung peritonealer Formationen. Berlin, 1891. 
 
 HERTWIG, O.: Lehrbuch der Entwickelungsgeschichte des Menschen und der Wirbeltiere. 
 Jena, 1906. 
 
 KEIBEL, F., and MALL, F. P.: Manual of Human Embryology, Vol. I, 1910. 
 
 KLAATSCH: Zur Morphologic der Mesenterialbildungen am Darmkanal der \Virbeltiere. 
 Morph. Jahrbuch, Bd. XVIII, 1892. 
 
 KOLLMAXX, J.: Lehrbuch der Entwickelungsgeschichte des Menschen. Jena, 1898. 
 
 KOLLMAXX, J.: Handatlas der Entwickelungsgeschichte des Menschen. Bd. II, 1907. 
 
 MALL, F. P.: Development of the Human Ccelom. Jour, of Morphol., Vol. XII, 1897. 
 
 PIERSOL. G. A.: Teratology. In Wood's Reference Handbook of the Medical Sciences. 
 1904. 
 
 RAVX, E.: Ueber die Bildung der Scheidewand zwischen Brust- und Bauchhohle in 
 Saugetierembryonen. Arch. f. Anat. u. Physiol., Anat. Abth., 1889. 
 
 STRAHL and CARIUS: Beitrage zur Entwickelungsgeschichte des Herzens und der 
 Korperhohlen. Arch. f. Anat. u. Physiol., Anat. Abth., 1889. 
 
 SWAEX, A.: Recherches sur le developpement du foie, du tube digestif, de Parriere- 
 cavite du peritoine et du mesentere. Premiere partie, Lapin. Jour, de VAnat. et de la 
 Physiol., T. XXXIII, 1896. Seconde partie. Embryons humains. T. XXXIII, 1897. 
 
 TOLDT, C.: Bau und Wachstumsveranderung der Gekrose des menschlichen Darm- 
 kanals. Denkschr. der kais. Akad. Wissensch. Wien. Math.-Naturivissen. Classe, Bd. 
 XLI, 1879. 
 
CHAPTER XV. 
 THE DEVELOPMENT OF THE UROGENITAL SYSTEM. 
 
 No other system in the body presents such peculiarities of development as 
 the urogenital system. In the first place, it is exceedingly complicated on ac- 
 count of its many parts. It is derived from both mesoderm (mesothelium and 
 mesenchyme) and entoderm. The urinary portion develops into a great com- 
 plex of ducts for the carrying off of waste products. The genital portion in 
 both sexes becomes highly specialized for the production and carrying off 
 of the sexual elements. In the second place, instead of one set of urinary organs 
 developing and persisting, three sets develop at different stages. The first 
 set (the pronephroi) disappears in part, but leaves certain structures which are 
 used, so to speak, in the development of the second. The second set (the meso- 
 nephroi) disappears for the most part, leaving, however, some portions which 
 are taken up in the development of the genital organs and other portions which 
 persist as rudimentary structures in the adult. The third set (the metanephroi 
 or kidneys) develops in part from the second and in part is of independent 
 origin. These conditions afford one of the most striking examples of the repe- 
 tition of the phylogenetic history by the ontogenetic, or, in other words, of von 
 Baer's law that an individual, in its development, has a tendency to repeat its 
 ancestral history; for the first and second sets of urinary organs in the human 
 embryo represent systems that are permanent in the lower Vertebrates. In the 
 third place, the ducts of the genital organs are not homologous in the two sexes. 
 In the male the ducts (deferent duct, duct of the epididymis, efferent ductules) 
 are derived from the second set of urinary organs; in the female they (the 
 oviducts) are derived from other ducts which develop in the second set of 
 urinary organs, but which are not functionally a part of the latter. 
 
 THE PRONEPHROS. 
 
 The pronephros, with the pronephric duct, is the first of the urinary organs 
 to appear. In embryos of 2-3 mm. there are two pronephric tubules on each 
 side, situated at the level of the heart. Although their mode of origin has not 
 been observed in the human embryo, it is probable, judging from observations 
 on lower Vertebrates, that they arise as evaginations of the mesothelium. The 
 part of the mesothelium involved is that adjacent to the intermediate cell mass 
 (Fig. 343) . (The intermediate cell mass is the portion of the mesoderm interven- 
 ing between the primitive segments and the unsegmented parietal and visceral 
 
 384 
 
THE DEVELOPMENT OF THE UROGENITAL SYSTEM. 
 
 385 
 
 layers; p. 84.) The more cephalic of the two tubules becomes hollow and 
 opens into the coelom; the more caudal is merely a solid cord of cells. Neither 
 tubule forms any connection with the pronephric duct. At each side of the root 
 of the mesentery a small elevation, which projects into the ccelom, probably 
 represents a rudimentary glomerulus. A glomerulus in the lower Vertebrates, 
 where the pronephros develops to a much greater degree than in Mammals, 
 contains tortuous vessels derived from branches of the aorta (Fig. 344). 
 The mesonephros (p. 389), beginning to develop almost as soon as the pro- 
 nephros and in the same relative position, forms a ridge which projects into the 
 coelom. The pronephric tubules thus become embedded in the mesonephric 
 ridge. 
 
 The pronephric duct begins to develop about the same time as the tubules. 
 It appears as a longitudinal ridge on the outer side of the intermediate cell mass 
 
 Sclerotorne Myotome 
 
 Ectoderm 
 
 Parietal 
 
 mesodenn 
 
 Visceral 
 mesoderm 
 
 Entodenrr 
 
 Pronephric 
 tubule 
 
 FIG. 343. Transverse section of a dog embryo with 19 primitive segments. Bonnet. 
 Section taken through sixth segment. 
 
 at the level of the heart and projects into the space between the mesoderm and 
 ectoderm. The ridge is at first solid but soon acquires a lumen, and gradually 
 extends to the caudal end of the embryo where it bends medially to open into 
 the gut. The origin of the caudal portion of the duct is a matter of dispute. 
 It comes in contact and fuses with the ectoderm, but whether in the higher ani- 
 mals the fusion is secondary or signifies a derivation from the ectoderm has 
 not been determined. When first formed, the entire duct lies on the outer side 
 of the intermediate cell mass, but later becomes embedded in the mesonephric 
 ridge. 
 
 The pronephric tubules are but transient structures and have no functional 
 significance in man and the higher Vertebrates. The ducts, however, remain 
 and become the ducts of the second set of urinary organs, the mesonephroi. 
 
 The significance of the pronephros can be understood only by reference to the conditions 
 in the lower animals. In the latter the pronephros acquires a relatively higher degree of de 
 
386 TEXT-BOOK OF EMBRYOLOGY. 
 
 velopment than in the higher forms. The tubules are segmentally arranged and are present 
 in many segments of the body. They open at their outer ends into the ducts, and at their 
 inner ends into the ccelom through ciliated funnel-shaped mouths or nephrostomes. Little 
 masses of mesoderm, containing tortuous vessels derived from branches of the aorta, form 
 glomeruli which project into the ccelom. Waste products are removed from the blood 
 through the agency of the glomeruli and are collected in the ccelom. They are then taken up 
 by the pronephric tubules and carried away by the ducts. In some of the Round Worms 
 there is not even a longitudinal duct, but the tubules open directly on the outer surface of 
 the body. In the lowest Fishes all the tubules on each side open into a longitudinal duct 
 which opens into the cloaca. In these lower forms of animal life the pronephroi constitute 
 the permanent urinary apparatus. In the ascending scale the mesonephroi appear (higher 
 
 x-x . u^.,' r^ 
 
 Pron. t. - 
 
 Glom. 
 
 FIG. 344. Diagram of the pronephric system in an amphibian. Bonnet. 
 
 C&L, Coelom; Glom., glomerulus, containing ramifications of a branch of the aorta; 
 
 Nch., notochord; Pron. t., pronephric tubule. 
 
 Fishes, Amphibia) and assume the function of carrying off waste products. The prone- 
 phroi also develop, but to a lesser degree. Still higher in the scale (Reptiles, Birds, Mam- 
 mals) the kidneys (metanephroi) appear and the mesonephroi lose their functional sig- 
 nificance. But even in the very highest Mammals the pronephroi appear, in a very rudimen- 
 tary form, in each individual in the earliest embryonic stages, thus repeating the ancestral 
 history. 
 
 THE MESONEPHROS. 
 
 The mesonephroi, which constitute the second set of urinary organs, appear 
 in embryos of 2.6-3.0 mm., immediately following the pronephroi. They be- 
 gin to develop just caudal to the pronephric tubules and in the same relative 
 position as the latter, that is, in the intermediate cell mass. Condensations* 
 appear in the mesenchyme and become more or less tortuous. At their inner 
 ends they form secondary connections with the mesothelium and at their outer 
 ends they join the pronephric duct which now becomes the mesonephric (or 
 Wolffian) duct. The cells acquire an epithelial character, lumina appear, 
 and the tortuous mesenchymal condensations thus become true tubules. Their 
 connections with the mesothelium soon disappear (Fig. 345). 
 
 *The term " condensation " is here used to mean increased density of tissue due mainly to 
 proliferation of cells. 
 
THE DEVELOPMENT OF THE UROGENITAL SYSTEM. 
 
 387 
 
 After the tubules are formed, other condensations of the mesenchyme appear 
 near their inner ends. A branch from the aorta enters each condensation and 
 breaks up into a number of smaller vessels which ramify inside, the entire 
 structure thus becoming a glomerulus. Each glomerulus pushes against the 
 corresponding tubule, the latter becoming flattened and then growing around 
 the glomerulus. In this way the glomerulus becomes surrounded by two layers 
 of epithelium, except at the point where the vessels enter, and the whole structure 
 the Malpighian corpuscle resembles very closely a renal corpuscle of the adult 
 
 Roof Spinal 
 
 plate ganglion Amnion 
 
 Glomerulus 
 
 Mesentery 
 
 Intestine 
 
 Post, cardinal vein 
 
 Mesonephric 
 (Wolffian) duct 
 
 Blood vessel 
 
 Mesonephric 
 (Wolffian) ridge 
 
 Coelom 
 
 Body wall with 
 umbilical vein 
 
 FIG. 345. From a transverse section of a sheep embryo of 21 days (15 mm.), 
 showing the developing mesonephros. Bonnet. 
 
 kidney. Waste products are removed from the blood through the agency of 
 the glomeruli and are carried to the ducts by the mesonephric tubules (Fig. 345). 
 The tubules themselves increase in length and become much coiled. Sec- 
 ondary and tertiary tubules also develop and become branches of the primary. 
 Whether these develop from condensations of the mesenchyme or as buds from 
 the primary tubules has not been determined. Each tubule consists of two 
 parts (i) a dilated part around the glomerulus, composed of large flat cells 
 and forming Bowman's capsule, and (2) a narrower coiled part leading from 
 
388 TEXT-BOOK OF EMBRYOLOGY. 
 
 the glomerulus to the duct and composed of smaller cuboidal cells (Fig. 345). 
 The primary mesonephric tubules are arranged segmentally, one appearing 
 in each segment as far back as the pelvic region. Thus the intermediate cell 
 mass may be considered as a series of nephrotomes, corresponding to the 
 sclerotomes and myotomes. The segmental character is soon lost, however, 
 owing to the inequality of growth between the mesonephros and the other seg- 
 mental structures, and to the development of the secondary and tertiary tubules. 
 As stated above, the first mesonephric tubules appear immediately caudal to 
 
 Mid-brain 
 
 B ^ -Fore-brain 
 Hind-brain 
 
 Branchial groove I 
 
 Heart- 
 
 i 
 
 - Lung 
 
 f V-fiPJF ' '" 1 -. -' ' 
 
 Intestine 
 
 Mesonephros- 
 
 ffl Genital ridge 
 
 Coelom tH^Ki^k 
 
 V \ HK3B& . t 
 
 j*- : / Body wall 
 
 Lower limb bud 
 
 Tail 
 
 FIG. 346. Human embryo of 5 weeks. The ventral body wall has been removed 
 to disclose the mesonephroi. Kollmann. 
 
 the pronephros. From this point their formation gradually progresses in a 
 caudal direction as far as the pelvic region. By the further development of the 
 primary and by the addition of the secondary and tertiary tubules and the 
 glomeruli, the mesonephros as a whole increases in size and forms a large 
 structure which projects into the ccelom on each side of the body, forming the 
 so-called mesonephric or Wolffian ridge. It reaches the height of its develop- 
 ment in the human embryo about the fifth or sixth week, at which time it ex- 
 tends from the region of the heart to the pelvic region (Fig. 346) . Each organ 
 
THE DEVELOPMENT OF THE UROGENITAL SYSTEM. 
 
 389 
 
 is attached to the dorsal body wall by a distinct mesentery which, at its cephalic 
 end, also sends off a band to the diaphragm the diaphragmatic ligament of 
 the mesonephros. The peritoneum is reflected over the surface of the meso- 
 nephros, and on the ventro-medial side the mesothelium becomes thickened to 
 form the genital ridge (p. 404; Figs. 314 and 346). The mesonephric ducts are 
 embedded in the lateral parts of the organs and extend throughout practically 
 their entire length. Since the ducts are identical with the pronephric ducts, 
 they open at first into the caudal end of the gut, or cloaca (p. 385; Fig. 360). 
 At a little later period, when the urogenital sinus is formed, they open at the 
 junction of the latter with the bladder (Fig. 363). Still later they open into the 
 
 Appendage t * 
 oftes ' 
 
 Testicle 
 
 Appendage of epididymis 
 
 Mesonephric duct 
 '(duct of epididymis) 
 
 -Paradidymis 
 
 ._ Aberrant ductule 
 
 _ Mullerian duct 
 
 _ Urogenital sinus 
 
 FIG. 347. Diagram representing certain persistent portions of the mesonephros 
 in the male (see table). Kollmann. 
 
 sinus itself (p. 400) . A description of their further development is best deferred 
 to the section on the male genital organs, since they become the genital ducts 
 (p. 416). 
 
 The mesonephroi function as urinary organs during the period of their 
 existence in the embryos of all higher Vertebrates. Excretory products are con- 
 veyed directly to the tubules by means of the glomeruli instead of being de- 
 posited in the ccelom and then taken up by the tubules, as is the case in func- 
 tional pronephroi (p. 386). The main excretory ducts are the same as in the 
 pronephroi. Aside from the vessels in the glomeruli the mesonephroi are ex- 
 ceedingly vascular organs. Large and small branches of the posterior cardinal 
 veins ramify among the tubules (Figs. 314 and 232). The blood undergoes 
 
390 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 purifying processes in its close contact with the tubules and is returned to the 
 heart by the posterior cardinals, or, after the cephalic ends of the latter atrophy, 
 by the subcardinals and the inferior vena cava (see p. 256; also Fig. 232, B). 
 There is thus present a true renal portal system, similar to the hepatic portal 
 system. 
 
 Although the mesonephroi become large functional organs during the earlier 
 stages of development, they atrophy and disappear for the most part, coinci- 
 dently with the appearance and development of the kidneys. The degeneration 
 begins during the sixth or seventh week and goes on rapidly until, by the end of 
 the fourth month, little remains but the ducts and a few tubules. The degenera- 
 
 o. t. a. 
 
 Ovd. 
 
 Epo. 1. 
 
 Epo. t. 
 
 FIG. 348. Diagram representing certain persistent portions of the mesonephros 
 
 in the female (see table). 
 
 Epo. /., Longitudinal duct of the epoophoron; Epo. t., transverse ductules of the epoophoron; O. /. a., 
 ostium abdominale tubse; Ovd., oviduct; X represents a small duct which, if present, leads 
 from the epoophoron to one of the fimbriae of the oviduct. 
 
 tive processes consist of (i) an ingrowth of connective tissue among the tubules, 
 (2) atrophy of the epithelium of the tubules, and (3) atrophy of the glomeruli. 
 The portions which remain differ in the two sexes, and since the remnants 
 are taken up in the formation of the male and female genital organs it seems 
 best to discuss them more fully under those heads (pp. 413, 416). The accom- 
 panying table, however, will give a clue to their fate (see also Figs. 347 and 
 348). A more comprehensive table will be found on p. 423. 
 
 Male Female 
 
 Mesonephros 
 
 f Cephalic part 
 
 Caudal part 
 
 Duct of mesonephros 
 
 Efferent ductules 
 (vasa efferentia) 
 
 Paradidymis 
 | Vasa aberrantia 
 f Deferent duct 
 I Ejaculatory duct 
 [ Seminal vesicles 
 
 Epoophoron 
 
 Paroophoron 
 
 Gartner's canals 
 
 The significance of the mesonephroi, which, as well as the pronephroi, are present in the 
 embryos of ail higher Vertebrates, can be understood only by referring to the conditions in the 
 lower Vertebrates. In the majority of the Fishes and in the Amphibia the mesonephroi con- 
 stitute the functional urinary organs of the adult and possess essentially the same structure as 
 
THE DEVELOPMENT OF THE UROGENITAL SYSTEM. 391 
 
 in the embryos of higher forms. Beginning in the Reptiles and continuing up through the 
 series of Birds and Mammals, another set of urinary organs the kidneys develops. The 
 meson ephroi also develop in these forms, even to a high degree, thus repeating the ancestral 
 history, but retain their original function only in the earlier embryonic stages. 
 
 THE KIDNEY (METANEPHROS). 
 
 The kidneys are the third set of urinary organs to develop. They assume 
 the function of the mesonephroi as the latter atrophy, and constitute the per- 
 manent urinary apparatus. Each kidney is derived from two separate anlagen 
 which unite secondarily. The epithelium of the ureter, renal pelvis, and 
 straight renal tubules (collecting tubules) is derived from the mesonephric duct 
 
 Mesonephros 
 
 Mesonephric duct 
 
 ^^L. ^ " ^I's^ / 
 
 Metanephric blastema 
 
 Metanephric blastema 
 (inner zone) 
 
 Primitive renal pelvis 
 
 Cloacal membrane -^& Urete 
 
 FIG. 349. From a reconstruction of the anlage of the kidney (metanephros) , etc., of a human 
 embryo at the beginning of the 5th week. Schreiner. 
 
 by a process of evagination. The convoluted renal tubules and glomeruli are 
 derived directly from the mesenchyme, and in this respect resemble the meso- 
 nephric tubules and glomeruli. 
 
 The Ureter, Renal Pelvis and Straight Renal Tubules. During the 
 fourth week (in embryos of about 5 mm.) a small, hollow, bud-like evagination 
 appears on the dorsal side of each mesonephric duct near its opening into the 
 cloaca. The evagination continues to grow dorsally in the mesenchyme 
 toward the vertebral column, and at the same time becomes differentiated 
 into two parts, a narrow stalk and a dilated terminal portion. The stalk is 
 the forerunner of the ureter, the dilated end is the primitive renal pelvis (Figs. 
 349 and 351). When the dilated end reaches the ventral side of the vertebral 
 
392 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 column it turns and grows cranially between the latter and the mesonephros. 
 The stalk (or ureter) elongates accordingly (Fig. 350). 
 
 About the fifth week, four evaginations from the primitive renal pelvis appear 
 one cephalic, one caudal and two central (Figs. 350 and 352). These may be 
 considered as straight renal tubules of the first order. The distal end of each 
 then enlarges to form a sort of ampulla, and from each ampulla two other 
 evaginations develop, forming tubules of the second order. From the ampulla 
 of each secondary tubule two tertiary tubules grow out; and this process con- 
 
 Mesonephros 
 
 Mesonephric duct 
 
 Junction of meson, 
 duct and ureter 
 
 Cephalic e vagi nation 
 
 .Metanephric blastema 
 Central evaginations 
 
 Caudal evagination 
 
 FIG. 350. From a reconstruction of the anlage of the kidney, etc., of a human 
 embryo of 11.5 mm. Schreiner. 
 
 tinues in a similar manner until twelve or thirteen divisions occur, the final 
 divisions occurring during the fifth month. The tubules grow into the mesen- 
 chyme which surrounds the pelvis and which forms the so-called metanephric 
 blastema, or nephro genie tissue (Fig. 351). 
 
 If the straight tubules were to remain in this condition, only four would open 
 directly into the pelvis, corresponding with the four primary evaginations. In 
 the adult, however, many hundreds open into the pelvis; consequently extensive 
 changes of the early condition must take place. These changes are similar to 
 
THE DEVELOPMENT OF THE UROGEXITAL SYSTEM. 
 
 393 
 
 the process by which the proximal ends of some of the blood vessels come to be 
 included in the wall of the heart (p. 235). The proximal ends of the tubules 
 become wider, the pelvis swells out, and the walls of the tubules become in- 
 cluded in the wall of the pelvis. In certain parts of the pelvic wall this process 
 goes on until deep bays the calyces are formed, into which a large number of 
 tubules open. In the other parts of the wall the process does not go so far, thus 
 leaving promontories the renal papilla upon which larger tubules or papil- 
 lary ducts open. The adult renal pelvis thus consists of the primitive pelvis plus 
 the proximal ends of the straight tubules. 
 
 Metanephric I 
 blastema | 
 
 Primitive 
 renal pelvis 
 
 Ureter 
 
 Mesonephric duct 
 Intestine 
 
 . Bladder 
 
 FIG. 351. From a transverse section of a human embryo at the beginning of the 5th week. 
 The plane of the section is indicated in Fig. 349. Schreiner. 
 
 The Convoluted Renal Tubules and Glomeruli. As stated above, 
 the metanephric blastema or nephrogenic tissue surrounds the renal pelvis 
 and the straight tubules. It represents a condensation of the mesenchyme and is 
 destined to give rise to the convoluted tubules and glomeruli. The cells of the 
 blastema in the region of the ampullae of the terminal straight tubules acquire 
 an epithelial character and become arranged in solid masses (Fig. 353). Each 
 mass unites with an ampulla and acquires a lumen, which becomes continuous 
 with the lumen of the straight tubule, then elongates and forms an S-shaped 
 structure (Figs. 354 and 355). The loop of the S nearer the straight tubules 
 elongates still more and grows toward the pelvis, parallel with the straight 
 
394 TEXT-BOOK OF EMBRYOLOGY. 
 
 tubules, to form Henle's loop. The part between Henle's loop and the straight 
 tubule elongates and becomes convoluted to form the proximal part of a con- 
 voluted renal tubule (second convoluted tubule). The part between the distal 
 end and Henle's loop elongates and becomes convoluted to form the distal part 
 of a convoluted renal tubule (first convoluted tubule) (Figs. 356 and 357). 
 
 To avoid confusion it may be well to call attention to the fact that what has here been 
 called the proximal part of a convoluted tubule corresponds with what is usually described as 
 the second or distal convoluted tubule, and that the distal part of a convoluted tubule 
 corresponds with the first or proximal convoluted tubule. In histology the distal and proxi- 
 mal convoluted tubules are spoken of in relation to the renal corpuscle, but in development 
 it is more convenient to speak of the terminal part of a tubule as its distal part. 
 
 Cephalic 
 evagination 
 
 Caudal 
 evagination 
 
 Ureter 
 
 FIG. 352. From a model of the primitive renal pelvis and the evaginations which form the cephalic, 
 central and caudal straight renal tubules of the first order. Human embryo of 4! months. 
 Compare with Fig. 350. Schreiner 
 
 A glomerulus develops in connection with the extreme distal end of a con- 
 voluted tubule or, in other words, with the distal loop of the S (p. 393). There 
 occurs here a further condensation of the mesenchyme, into which grows a 
 branch from the renal artery. This, as the afferent vessel of the glomerulus, 
 breaks up into several arterioles, each of which gives rise to a tuft of capillaries. 
 These tufts are separated from one another by somewhat more mesenchymal 
 tissue than separates the capillaries within a tuft. The tufts with the asso- 
 ciated mesenchymal tissue constitute a glomerulus, and it is the mesenchymal 
 septa between the tufts that give to the glomerulus its characteristic tabulated 
 appearance. The capillaries of each tuft empty into an arteriole, and the 
 several arterioles unite to form the efferent vessel of the glomerulus, which passes 
 out along side of the afferent vessel. The renal tubule becomes flattened on the 
 side next the condensation of the mesenchyme, and as the glomerulus develops, 
 the epithelium of the tubule grows around it except at the point where the blood 
 
 \ 
 
THE DEVELOPMENT OF THE UROGENITAL SYSTEM. 
 
 395 
 
 vessels enter and leave. Thus a double layer of epithelium comes to surround 
 the glomerulus, the space between the two layers being the extreme distal part 
 of the lumen of a renal tubule. The inner layer is closely applied to the surface 
 
 I Anlagen of 
 > convoluted 
 renal tubules 
 
 Renal pelvis 
 
 Capsule 
 
 Anlage of 
 
 convoluted renal tubule 
 
 Ampulla of 
 straight renal tubule 
 
 FIG. 353. Sagittal section of the anlage of the left kidney in a rabbit embryo of 15 days. Schreiner. 
 The straight renal tubules (sections of which are shown) are embedded in the metanephric blastema. 
 
 Condensations of the latter form the anlagen of the convoluted renal tubules. At the left 
 
 of the figure several mesonephric tubules are shown. 
 
 Amp. 
 
 Con. r. t. 
 
 Met. bl. 
 
 Con. r. t. 
 
 FIG. 354. From a section of the kidney of a human foetus of 7 months. Schreiner. 
 
 Amp., Ampulla of a straight renal tubule; Con. r. /., anlagen of convoluted renal tubules, above and 
 
 between which are two ampullae (compare Fig. 355); met. bl., metanephric blastema. 
 
 of the glomerulus and even dips down into the latter between the tufts. The 
 outer layer forms Bowman's capsule, the flat epithelium of which passes over 
 into the cuboidal epithelium of the "neck" of the tubule, and this in turn is 
 
396 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 Pros, convoluted tubule 
 Dist. convoluted tubul 
 Henle's loo 
 
 FIG. 355- 
 
 Ampulla of straight tubule 
 
 Henle's loop 
 
 Distal part of 
 convoluted tubule 
 
 Bowman's capsule 
 
 Proximal part of 
 convoluted tubule 
 
 Distal part of 
 convoluted tubule 
 
 "Neck" 
 Bowman's capsule 
 
 FIG. 356. 
 
 Prox. convoluted tubule 
 Dist. convoluted tubule 
 Henle's loop 
 
 Prox. convoluted tubule^ 
 Bowman's capsule 
 Straight tubule 
 
 Prox. convoluted tubule 
 Dist. convoluted tubule 
 
 Prox. convoluted tubule 
 
 Dist. convoluted tubule 
 Bowman's capsule 
 
 Ascending } 
 
 > arm of Henle's loop 
 Descending J 
 
 FIG. 357. 
 
 F;GS - 355> 35 6 and 357- From reconstructions of convoluted renal tubules in successive 
 stages of development. Stoerk. 
 
THE DEVELOPMENT OF THE UROGEXITAL SYSTEM. 397 
 
 continuous with the pyramidal epithelium of the distal convoluted tubule. 
 The entire structure is a renal corpuscle. The formation of renal corpuscles 
 begins in embryos of 30 mm. and continues until after birth. 
 
 The Renal Pyramids and Renal Columns. The tubules arising from 
 the four primary evaginations of the renal pelvis together form four distinct 
 groups or primary renal (Malpighian) pyramids one cephalic, one caudal, and 
 two central. The central pyramids are crowded in between the end pyramids, 
 (cephalic and caudal) and do not develop as rapidly as the latter which soon 
 bend around toward the ureter, thus resulting in the formation of the convex 
 side of the kidney and a depression or hilus opposite (compare Figs. 352 and 
 358) . Between these four pyramids the mesenchyme remains for some time as 
 
 Primary renal pyramid 
 
 'Primary renal column 
 Cephalic straight tubule- 
 Primary renal pyramid 
 Central straight tubule = 
 
 ___^^^^^_^^_^^^^_ Primary renal column 
 Caudal straight tubule 
 
 Urett 
 
 Primary renal pyramid 
 FIG. 358. Frontal section of the kidney of a human foetus of 3! months (10 cm.). Hauch. 
 
 rather distinct septa, forming the primary renal columns (columns of Bertini) 
 which are marked by corresponding depressions on the surface of the kidney 
 and extend to the renal pelvis. The four primary pyramids may be considered 
 as lobes (Fig. 358). It should also be stated that the parts of the tubules 
 derived from the mesenchyme form the bases of the renal pyramids. Be- 
 tween the groups of straight tubules derived from evaginations of the second or 
 third order (see p. 392) there are also septa of mesenchyme which divide each 
 primary pyramid into two or three secondary pyramids. These septa may 
 be considered as secondary renal columns (Fig. 359). Thus the entire kidney 
 is divided into from eight to twelve secondary pyramids. Tertiary renal 
 columns then divide incompletely the secondary pyramids into tertiary pyra- 
 
398 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 mids. These are apparent on the surface of the kidney and constitute the 
 surface tabulation, but are not clearly denned in the interior. 
 
 The formation of renal papillae (p. 393) corresponds to the formation of 
 pyramids only to a certain point, for some of the tertiary pyramids appear only 
 near the surface and consequently do not have corresponding papillae. This 
 accounts for the fact that frequently the number of pyramids apparent on the 
 surface does not correspond with the number of papillae. The surface lobula- 
 tion is very plainly marked in kidneys up to and for a short time after birth. It 
 then disappears and the surface becomes smooth. At the same time the con- 
 nective (mesenchymal) tissue of the renal columns is largely replaced by the 
 
 Secondary 
 
 renal 
 column Secondary 
 
 renal 
 
 pyramid Secondary 
 renal 
 column 
 
 FIG. 359. Frontal section of the kidney of a human foetus of 19 weeks (17.5 cm.). Hauch. 
 
 epithelial elements of the gland so that in the adult kidney the columns are not 
 clearly denned. 
 
 The capsule of the kidney is derived from the mesenchyme which surrounds 
 the anlage of the organ (Fig. 353) . This mesenchyme is transformed into fibrous 
 connective tissue and a small amount of smooth muscle, forming a layer which 
 closely invests the kidney and dips into the hilus where it surrounds the blood 
 vessels and the end of the ureter. The connective tissue and muscle of the 
 ureter are also derived from the mesenchyme. 
 
 CORTEX AND MEDULLA. As the convoluted renal tubules develop in the 
 metanephric blastema (p. 393), they form a cap-like mass around the group of 
 
THE DEVELOPMENT OF THE UROGENITAL SYSTEM. 399 
 
 straight tubules. This is the beginning of the renal cortex. A true cortex, 
 however, can be spoken of only after the appearance of the glomeruli (in 
 embryos of 30 mm.). Its peripheral boundary is the capsule, and the renal 
 corpuscles nearest the pelvis mark its inner boundary. The mass of straight 
 tubules forms the bulk of the medulla. It does not at this stage contain Henle's 
 loops, the latter developing later (during the fourth month). Both cortex 
 and medulla increase until the kidney reaches its adult size. The cortex 
 increases relatively faster than the medulla up to the seventh year; after 
 this the increase is practically equal. The medullary rays are probably 
 secondary formations, being formed by groups of straight tubules which 
 grow out into the cortex; later, ascending arms of Henle's loops are added to 
 these groups. 
 
 Some of the glomeruli of the first generation are much larger than any 
 found in the adult. In some of the lower Mammals these "giant" glomeruli 
 disappear and it is probable that the same occurs in the human embryo. Some 
 of the tubules also degenerate and disappear. The cause of these phenomena 
 is not known. 
 
 Changes in the Position of the Kidneys. As has already been described 
 (p. 391), the kidney buds first grow dorsally from the mesonephric ducts 
 toward the vertebral column. They then grow cranially, with a corresponding 
 elongation of the ureters, and in embryos of 20 mm. they lie for the most part 
 cranial to the common iliac arteries. This migration continues until the time 
 of birth when the cephalic ends of both kidneys reach the eleventh thoracic ver- 
 tebra. When the kidneys begin to move cranially the hilus is directed caudally. 
 Later they rotate and the hilus is turned toward the medial sagittal plane. 
 
 Since the ureter, renal pelvis and straight tubules develop from the mesonephric ducts, 
 and since the convoluted tubules and glomeruli develop directly from the same tissue as the 
 mesonephric tubules, namely, the mesenchyme, the renal tubules may be said to represent 
 the third generation of urinary tubules. But no definite reason for the appearance of the 
 third generation can be given. The atrophy of the mesonephroi would, of course, make 
 necessary the compensatory development of new structures; but this only carries the problem 
 a step further back, for the cause of the atrophy of the mesonephroi is not clear. In regard 
 to this atrophy, however, there is a suggestion of a cause in the fact that in the Amphibia 
 the mesonephroi are in part used for conveying the sexual elements, which leaves the meso- 
 nephroi less free to function as urinary organs. Possibly the loss of freedom to function leads 
 to the development of new structures the kidneys in the higher forms (Reptiles, Birds 
 and Mammals). In these forms the kidneys assume the urinary function after the early 
 embryonic stages, and only the ducts and a part of the tubules of the mesonephroi persist in 
 the male to convey the sexual elements. Thus the persistent parts of the mesonephroi as- 
 sume a new function as the old one is lost. But, on the other hand, complications arise 
 on account of the fact that in the female the sexual products are carried off by another set 
 of ducts (the Mullerian ducts), which develop in both sexes but disappear in the male, 
 while the mesonephroi and their ducts disappear almost entirely. 
 
400 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 THE URINARY BLADDER, URETHRA AND UROGENITAL SINUS. 
 
 As described elsewhere, the allantois appears at an early stage as an evagi- 
 nation from the ventral side of the caudal end of the primitive gut (Fig. 282), 
 grows out into the belly stalk, and finally becomes enclosed in the umbilical cord 
 (p. 114). As the embryo develops, the proximal end of the allantois becomes 
 elongated to form a stalk or duct which extends from the caudal end of the 
 gut to the umbilicus (Fig. 285). The portion of the gut immediately caudal to 
 the attachment of the allantoic duct becomes dilated to form the cloaca which 
 at first is a blind sac, its cavity being separated from the outer surface of the 
 embryo by the cloacal membrane (Fig. 360) . The latter is composed of a layer of 
 entoderm and a layer of ectoderm, with a thin layer of mesoderm between. The 
 cloaca then becomes separated into two parts a larger ventral part which forms 
 
 Intestine Kidney bud 
 
 Mesonephric duct 
 
 Urachus 
 
 Cloaca 
 
 Cloacal membrane 
 
 Caudal gut 
 
 Notochord \ 
 
 Neural tube 
 
 FIG. 360. From a model of the cloaca and the surrounding structures in a 
 human embryo of 6.5 mm. Keibel. 
 
 the urogenital sinus and a smaller dorsal part which forms the rectum. This 
 is accomplished by a fold or ridge which grows from the lateral wall into the 
 lumen and meets and fuses with its fellow of the opposite side. The fusion be- 
 gins at the cephalic end, in the angle between the allantoic duct and the gut, 
 and gradually proceeds caudally until the separation is complete as far as the 
 cloacal membrane. The mass of tissue forming the partition is called the uro- 
 rectaljold, (Fig. 361) . The openings of the mesonephric ducts, which primarily 
 were situated in the lateral cloacal wall (p. 389), are situated after the separation 
 in the dorso-lateral wall of the urogenital sinus (compare Figs. 360, 361, 362). 
 During the separation of the urogenital sinus from the rectum, certain 
 changes take place in the proximal ends of the mesonephric ducts and ureters. 
 The ends of the ducts become dilated and are gradually taken up into the wall of 
 the sinus. This process of absorption continues until the ends of the ureters are 
 included, with the result that the ducts and ureters open separately, the latter 
 
THE DEVELOPMENT OF THE UROGEXITAL SYSTEM. 401 
 
 slightly cranial and lateral to the former. (Compare Figs. 362 and 363.) This 
 condition is reached in embryos of 12 to 14 mm. The point at which these two 
 sets of ducts open marks the boundary between a slightly larger cephalic part 
 of the sinus, the anlage of the bladder, and a smaller caudal part which becomes 
 the urethra and urogenital sinus (Fig. 363). 
 
 After the second month the bladder becomes larger and more sac-like, and 
 the openings of the ureters migrate farther cranially to their final position. The 
 lumen of the bladder is at first continuous with the lumen of the allantoic duct, 
 but the duct degenerates into a solid cord of cells, the urachus. The latter 
 degenerates still further and finally remains only as the middle umbilical liga- 
 
 Urorectal fold Mesonephric duct 
 
 ^^^ ^^^^ Kidney bud. 
 
 Urachus 
 
 Cloaca 
 Urogenital sinus 
 
 Cloacal membrane ~ * Rectum 
 
 audal gut 
 
 FIG. 361. From a model of the cloacal region of a human embryo slightly older than 
 
 that shown in Fig. 360. Keibel. 
 
 The arrow points to the developing partition (urorectal fold) between the rectum and urogenital 
 sinus. The opening of the mesonephric duct into the urogenital sinus is indicated by a 
 small seeker. 
 
 ment. It seems quite probable that the bladder is derived almost wholly from 
 the cloaca. A small part arises from the inclusion of the ends of the mesoneph- 
 ric ducts. If any part is derived from the allantoic duct, it is only the apex. 
 After the bladder begins to enlarge, the adjacent portion of the urogenital 
 sinus becomes slightly constricted. This marks the beginning of the urethra. 
 In the female the constricted part represents practically the entire urethra. 
 In the male it represents only the proximal end, the other portion developing 
 in connection with the penis (p. 428). The urogenital sinus is narrow and 
 tubular at its junction with the urethra; more distally it is wider and is shut off 
 from the exterior by the cloacal membrane. After the embryo reaches a length 
 of 1 6 to 17 mm., the membrane ruptures and the sinus opens on the surface. 
 
402 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 The narrow part of the sinus is gradually taken up into the wider, resulting in 
 the formation of a sort of vestibule. In both sexes the urethra opens into the 
 deeper end of the vestibule. In the male the mesonephric (seminiferous) 
 
 Cloaca 
 (undivided portion) 
 
 Cloacal membrane 
 
 Tail 
 
 Mesonephric ducts 
 Ccelom 
 
 Primitive renal pelvis 
 
 Rectum 
 
 FIG. 362. From a reconstruction of the caudal end of a human embryo 
 of 11.5 mm. (4^ weeks). Keibel. 
 
 Umbilical artery 
 Bladder 
 
 Symphysis pubis 
 Urogenital si 
 
 Genital tubercle 
 Urethra 
 
 Ovary 
 
 Broad ligament 
 of uterus 
 
 - Mullerian duct 
 
 Mesonephric duct 
 Ureter 
 
 Recto-uterine 
 excavation 
 
 Rectum 
 
 Tail 
 
 FIG. 363. From a reconstruction of the caudal end of a human embryo 
 
 of 25 mm. (8^-9 weeks). Keibel. 
 The asterisk (*) indicates the urorectal fold. 
 
 ducts open near the external orifice. In the female the opening of the develop- 
 ing vagina is situated on the dorsal side near the external orifice. 
 
 The epithelium of the prostate gland is derived by evagination from the proxi- 
 
THE DEVELOPMENT OF THE UROGENITAL SYSTEM. 403 
 
 mal part of the urethra. The first evagination appears during the third month. 
 In the male the process continues to form a rather large gland; in the female the 
 structure remains in a rudimentary condition. During the fourth month two 
 evaginations arise from the urethra and develop into the bulbo-urethral 
 (Cowper's) glands in the male, into the larger vestibular (Bartholin's) glands in 
 the female. 
 
 From the course of development it is seen that the epithelium of most of the 
 bladder, of the female urethra and proximal end of the male urethra, of the 
 
 Germinal j|a . Stroma 
 
 epithelium t mm (mesenchyme) 
 
 (mesothelium) 
 
 FIG. 364. Transverse section through the germinal epithelium of a pig embryo of n mm. Nagel. 
 
 The larger cells in the epithelium represent the sex cells, the smaller ones the 
 
 undifferentiated mesothelial cells. 
 
 prostate, of the urogenital sinus, and of the bulbo-urethral and vestibular 
 glands is of entodermal origin. A very small part of the bladder epithelium 
 is of mesodermal origin, since the proximal ends of the mesonephric ducts, 
 which are mesodermal derivatives, are taken up into the wall. All the connec- 
 tive tissue and smooth muscle associated with these organs are derived from 
 the mesoderm (mesenchyme) which surrounds the anlagen. 
 
 THE GENITAL GLANDS. 
 The Germinal Epithelium and Genital Ridge. 
 
 At a very early stage in the formation of the mesonephros, a narrow strip 
 of mesothelium extending along the medial surface becomes thicker and the 
 cells become arranged in several layers (Figs. 314 and 346). The cells become 
 differentiated into two kinds (i) small cuboidal cells with cytoplasm which 
 stains rather intensely, and (2) larger spherical cells with clearer cytoplasm and 
 
404 TEXT-BOOK OF EMBRYOLOGY. 
 
 large vesicular nuclei (Fig. 364). The latter are the sex cells; and the whole 
 epithelial (mesothelial) band is known as the germinal epithelium. The sex 
 cells are destined to give rise to the sexual elements in the female to the ova, 
 in the male to the spermatozoa. In the earlier stages, however, it is impossible 
 to determine whether the sex cells will give rise to male or female elements. 
 The differentiation of sex and the corresponding histological differentiation of 
 the sex cells occur at a later period. 
 
 In his recent work on the ovary and testis in Mammals, Allen has ob- 
 served in very early stages (pig embryos of 6 mm., rabbit embryos of 13 days) 
 certain large cells, with large clear nuclei, in the mesenchymal tissue of the 
 mesentery, outside of the genital ridge. These, from their resemblance to the 
 sex cells within the genital ridge, should probably also be classed as sex cells. 
 Their origin in these animals, however, is not known with certainty; but 
 the fact that in turtle embryos Allen has found cells of a similar character 
 apparently migrating from the entoderm through the mesoderm to the site of 
 the genital glands suggests the possibility that they are entodermal derivatives. 
 It is doubtful whether these aberrant sex cells take part in the development of 
 the mature sexual elements, the latter in all probability being derived from 
 the sex cells of the mesothelium of the genital ridge. 
 
 Beard, Eigenmann, Rabl, Woods, and others, have described sex cells, undoubtedly 
 homologous with the aberrant sex cells mentioned above, as occurring in various regions of 
 the embryos of certain Fishes. These investigators also assert that the sex cells become 
 specialized and, so to speak, segregated at a very early period of development, even at the 
 stage of blastomere formation. Beard contends that the early differentiated sex (or germ) 
 cells are significant in the origin of certain teratomata (see Chapter on Teratogenesis). 
 
 The cells of the germinal epithelium increase in number by mitotic division 
 and, for some time at least, the sex cells continue to increase in number by 
 differentiation from the small cuboidal (indifferent) cells, as indicated by the 
 presence of intermediate stages between the two types. The germinal epi- 
 thelium soon becomes separated into two layers (i) a superficial layer which 
 retains its epithelial character and contains the sex cells, and (2) a deeper layer 
 composed of smaller cells which resemble those of the mesenchyme and which 
 give rise to a part, at least, of the stroma of the genital glands. The elevation 
 formed by these two layers projects into the body cavity from the medial side 
 of the mesonephros and constitutes the genital ridge (Fig. 346). From the 
 superficial epithelial layer, columns or cords of cells, containing some of the 
 sex cells, grow into the underlying tissue. This ingrowth, however, does not 
 occur equally in all parts of the genital ridge, for three fairly distinct regions 
 can be recognized. In the cephalic end comparatively few columns appear, 
 but these few grow far down into the underlying tissue and constitute the rete 
 cords. In the middle region a greater number of columns grow into the 
 
THE DEVELOPMENT OF THE UROGEXITAL SYSTEM. 
 
 405 
 
 stroma, forming the sex cords. In the caudal region there are practically no 
 columns. At first the line of demarkation between the cell columns and the 
 stroma is not clearly defined^ 
 
 The changes thus far described are common to both sexes and are completed 
 during the fourth or fifth week. The genital ridges or anlagen of the genital 
 glands constitute "indifferent" structures which later become differentiated into 
 either ovaries or testicles. 
 
 Differentiation of the Genital Glands. 
 
 After the fourth or fifth week, certain changes occur in the genital ridges 
 which differ accordingly as the ridges form ovaries or testicles. While the 
 differences are at first not particularly obvious, there are four which become 
 clearer as the changes progress, (i) If the ridge is to become a testicle, the 
 cells of the surface epithelium become arranged in a single layer and become 
 
 Rete cords 
 (Rete testis) 
 
 Mesorchium 
 
 Mesothelium 
 
 Tunica 
 albuginea 
 
 Mesonephros 
 
 Sex cords 
 (convoluted semin- 
 iferous tubules) 
 
 Glomerulus 
 
 FIG. 365. Transverse section of the left testicle of a pig embryo of 62 mm. Bonnet. 
 
 flat. (2) In a developing testicle a layer of dense connective tissue grows be- 
 tween the surface epithelium and the sex cords, forming the tunica albuginea. 
 
 (3) In a testicle there also appears a sharper line of demarkation between the 
 cell columns and the stroma, and the latter shows a more extensive growth. 
 
 (4) Another feature of the testicle is that the sex cells begin to be less con- 
 spicuous and do not increase further in size, but come to resemble the other 
 epithelial elements. The ovarian characters are to a certain extent the oppo- 
 site, (i) The surface epithelium does not become flattened. (2) A layer of 
 connective tissue, corresponding to the albuginea of the testicle, grows be* 
 
406 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 tween the epithelium and the deeper parts, but is of a looser nature. (3) There 
 is a less sharp line of demarkation between the cell columns and the stroma. 
 (4) The sex cells continue to increase in size and become more conspicuous. 
 (Compare Figs. 365 and 366.) 
 
 During these processes of development, the anlage of each genital gland be- 
 comes more or less constricted from the mesonephros and finally is attached only 
 by a thin sheet of tissue the mesovarium in the female or the mesorchium in the 
 
 Oviduct 
 
 (Ostium abdom- 
 
 inale tubae) 
 
 Cortex 
 
 Medullary cords 
 
 (Medulla) ~ 
 
 -4 Epoophoron 
 
 Rete cords 
 - (Rete ovarii) 
 
 -Mesonephros 
 
 Oviduct 
 FIG. 366. Longitudinal section of the ovary of a cat embryo of 94 mm. Semidiagrammatic. Coert. 
 
 male (p. 419). At the same time the anlage grows more rapidly in thickness 
 than in length and assumes an oval shape. 
 
 The Ovary. As stated above, a layer of loose connective tissue, correspond- 
 ing to the albuginea of the testicle, grows in between the surface epithelium and 
 the cell columns (sex cords) and effects a more or less complete separation. 
 The sex cords are thus pushed farther from the surface, become more clearly 
 marked off from the surrounding stroma and constitute the so-called medullary 
 cords. The cortex of the ovary at this stage is represented only by the surface 
 (germinal) epithelium, which is composed of several layers of cells and contains 
 
THE DEVELOPMENT OF THE UROGENITAL SYSTEM. 407 
 
 numerous sex cells in various stages of differentiation (Fig. 367). The 
 rete cords which arise in the cranial end of the "indifferent" gland (p. 404) 
 come to lie in what will be the hilus of the ovary. The ovary may thus be 
 said to be composed of two parts (i) the rete anlage and (2) the stratum ger- 
 minativum. The latter is subdivided by the albuginea into (a) medulla and 
 (b) cortex. 
 
 i. The rete cords develop into a group of anastomosing trabeculae which con- 
 stitute the rete ovarii, situated in the hilus but nearer the cephalic end of the 
 gland (Fig. 366). They are the homologues of the rete testis. The cells com- 
 posing them are smaller and darker than those of the medullary cords. Sprouts 
 grow out from the rete cords and unite with the medullary cords and the meso- 
 nephric tubules. (The same process occurs in the testicle, where the rete cords 
 give rise to the functional rete testis and straight seminiferous tubules.) In 
 
 Cortex :^R**.v, '.'*\\ V"- f&.f-'r'Ji^^^^m^^. Mesothelium 
 
 (Germinal epithelium) 
 
 Medulla -i 
 
 Mesovarium 
 
 Re te ovarii 
 
 FIG. 367. Transverse section of the ovary of a fox embryo. Biihler in Hertwig's Handbuch. 
 The large clear cells are the primitive ova. 
 
 some of the cords lumina appear and are lined with irregular epithelium. 
 Such a condition represents the height of their development in the ovary. 
 From this time on, they degenerate and finally disappear. The time of their 
 disappearance varies in different individuals; they usually persist until birth, 
 sometimes until puberty. 
 
 Formerly it was thought that the rete cords were derived from the meso- 
 nephric tubules and entered the genital glands secondarily. More recent re- 
 searches have demonstrated quite conclusively, however, that they are deriva- 
 tives of the germinal epithelium and unite with the mesonephric tubules 
 secondarily. 
 
 2 (a). The medullary cords are composed of small epithelial cells, contain a 
 number of larger sex cells or primitive ova, and are surrounded by stroma 
 (Figs. 367, 368). They are connected with the rete cords and in some places 
 with the germinal epithelium. During foetal life they give rise to primary 
 ovarian (Graafian) follicles; later they degenerate and finally disappear. 
 
408 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 2(b). The cortex of the ovary, as stated above, at first consists of several 
 layers of small, darkly staining cells, among which are many large, clearer sex 
 cells or primitive ova (Fig. 367). From the epithelium, masses or cords of cells 
 grow into the underlying tissue, carrying with them some of the primitive ova. 
 These masses are known as P finger's egg cords. In some cases several ova are 
 grouped together, forming egg nests (Fig. 368). The epithelial cells are the 
 progenitors of the follicular cells and constantly undergo mitotic division. The 
 primitive ova, on the other hand, increase in size and their nuclei show distinct 
 intranuclear networks. 
 
 The egg cords become separated from the surface epithelium and are 
 broken up so that in most cases a single ovum is surrounded by a single layer of 
 
 Germinal 
 epithelium 
 
 Cortex 
 
 Medulla 
 
 FIG. 368. From a section through the ovary of a human foetus of 4 months. Meyer-Ruegg, Btih/er. 
 The large cells are the primitive ova. 
 
 epithelial cells. This constitutes a primary Graafian follicle. Rarely a follicle 
 contains more than one ovum. In the case of the egg nests, the ova may become 
 separated, or two or more may lie in one follicle. If two or more ova are 
 present at first in any follicle, usually only one continues to develop and the 
 others either degenerate or are used as nutritive materials. In very rare cases, 
 however, two ova may develop in a single follicle, but whether they reach 
 maturity or not is uncertain. The formation of egg cords is usually com- 
 pleted before birth, but in some cases may continue for one or two years after 
 birth. During the processes thus far described, the stroma also has been in- 
 creasing, and the egg cords and follicles come to be separated by a considerable 
 amount of connective tissue. The germinal epithelium becomes reduced to a 
 single layer of cuboidal cells. 
 
THE DEVELOPMENT OF THE UROGENITAL SYSTEM. 
 
 409 
 
 Each primary ovarian follicle, containing a primitive ovum (egg cell, sex cell) , 
 is composed of a single layer of flat or cuboidal cells, plus a layer of stroma 
 which gives rise to the theca folliculi. As the ovum continues to enlarge, the 
 follicular cells become higher and arranged in a radial manner (Fig. 369, a) . By 
 proliferation, the follicular cells come to form several layers, the innermost 
 layer retaining the radial character and forming the zona radiata. The inner or 
 basal ends of the cells of the zona radiata become clear to form the zona pellucida. 
 In the latter, radial striations appear which have been described as minute 
 
 c d 
 
 FIG. 369. Four stages in the development of the ovarian (Graafian) follicle 
 
 From photographs of sections of a cat's ovary Hertivig. 
 
 The ovum is not shown in a, b and c. 
 
 channels in the cells, through which nutriment may pass to the ovum. After 
 the follicular epithelium has become several layers thick, a fluid substance 
 known as the liquor folliculi, and probably derived from the cells themselves, 
 comes to lie in little pools among the cells (Fig. 369, b and c ) . While the follicle 
 as a whole enlarges, these pools gradually coalesce and form a single large pool 
 which fills the interior of the follicle (Fib. 369, d). Thus the epithelium is 
 crowded out toward the periphery where it forms a layer several cells in thick- 
 ness, known as the stratum granulosum. The ovum itself, with the zona radiata 
 and some other surrounding cells, is also crowded off to the periphery of the 
 
410 TEXT-BOOK OF EMBRYOLOGY. 
 
 follicle. The little elevation of the stratum granulosum in which the ovum 
 is embedded is known as the cumulus ovigerus or germ hill (see Fig. 18). 
 
 The primary ovarian follicles at first lie rather near the surface of the ovary, 
 but as they enlarge and as the ovary enlarges they come to lie deeper. As the 
 follicle approaches maturity it increases greatly in size (5=fc mm.) and finally 
 extends through the entire thickness of the cortex, its theca touching the tunica 
 albuginea. 
 
 In speaking of the development of the follicles, it must be remembered that 
 they develop slowly and do not reach maturity until near the age of puberty, and 
 furthermore that one, or very few at most, reach maturity at the same time. In 
 other words, when one follicle has reached maturity there are all intermediate 
 stages of development between this and the primitive follicles. When a follicle 
 reaches maturity it ruptures at the surface of the ovary and the ovum is set free 
 (p. 30). The ovum itself undergoes certain changes by which the somatic 
 number of chromosomes is reduced one-half (p. 21). It then unites with the 
 mature spermatozoon, which also contains one-half the somatic number of 
 chromosomes, and forms the starting point, so to speak, for a new individual. 
 At this point the processes by which an individual is carried through its life 
 period from its beginning as a fertilized ovum to the time when it produces the 
 next generation of mature sexual elements are ended. The developmental 
 cycle of one generation is complete. 
 
 It has been estimated that approximately 36,000 primitive ova appear in 
 each human ovary. Since, as a rule, only one ovum escapes from the ovary at a 
 menstrual period or between two succeeding periods, it is obvious that the vast 
 majority of these never reach maturity. They probably degenerate, and, as a 
 matter of fact, atretic follicles may be found in an ovary at any time. 
 
 CORPUS LUTEUM. After the rupture of the mature follicle at the surface of 
 the ovary and the escape of the ovum and liquor folliculi, blood from the rup- 
 tured vessels fills the interior of the follicle and forms a clot the corpus h&mor- 
 rhagicum. The cells of the stratum granulosum proliferate and migrate into 
 the clot and gradually form a mass which replaces the blood. It is held by some 
 that the cells are derived from the theca folliculi. Whatever their origin, they 
 become infiltrated with a fatty substance known as lutein. Trabeculse of 
 connective tissue grow into the mass of cells, carrying small blood vessels with 
 them. The (lutein) cells disintegrate and the products of disintegration are 
 probably carried off by the blood, and finally the entire corpus luteum is trans- 
 formed into a mass of connective tissue (Figs. 19, 20 and 21, and p. 31). 
 
 Whether the escaped ovum is fertilized or not has an influence upon the 
 development of the corpus luteum. In case of fertilization, the corpus luteum 
 becomes quite large, increasing in size up to the fourth month of pregnancy, and 
 then degenerates. In case the ovum is not fertilized, the corpus luteum re- 
 
THE DEVELOPMENT OF THE UROGENITAL SYSTEM. 411 
 
 mains smaller. In both cases, however, the histological changes are essentially 
 the same (p. 33). 
 
 The Testicle. The processes that give rise to the "indifferent" genital 
 glands have been described (p. 403 et seq.) . It has also been stated that there 
 appears during the fourth or fifth week a structure that forms one of the char- 
 acteristic features of the testicle. This is a layer of dense connective tissue 
 which develops beneath the surface epithelium and constitutes the tunica 
 albuginea (p. 405), and which separates the surface epithelium from the sex 
 cords (Fig. 365) . The epithelium becomes reduced to a single layer of flat cells, 
 although the cells on the tip of the gland usually remain high until after birth. 
 Naturally this epithelium is continuous around the hilus of the testicle with the 
 epithelium (mesothelium) of the abdominal cavity. Within the gland are the 
 sex cords the progenitors of the convoluted seminiferous tubules, which become 
 quite distinctly marked off from the stroma by a basement membrane. In the 
 
 Interstitial cell Sex cell 
 
 - 
 *^- * ~* -~, *.*--** 
 
 m 
 
 Mesothelium *Tunica Supporting cell 
 
 albuginea (of Sertoli) 
 
 FIG. 370. From a section of the testicle of a human foetus of 35 mm., showing a developing 
 convoluted seminiferous tubule. Meyer-Rilegg, Biihler. 
 
 hilus region lie the rete cords the progenitors of the rete testis and the straight 
 seminiferous tubules (Fig. 365) . The rete cords of the testicle are homologues of 
 the rete cords of the ovary, and are derivatives of the germinal epithelium on the 
 cephalic portion of the "indifferent" gland (p. 404). 
 
 The sex cords at first are solid masses composed of several layers of cells. 
 The latter are of two kinds, as in the ovary (i) smaller, darkly staining indiffer- 
 ent cells, and (2) larger, clearer sex cells (Fig. 370). The sex cells lose their 
 clearness and come to resemble again the undifferentiated epithelial cells. 
 They represent the spermatogonia, which correspond to the primitive ova. 
 The spermatogonia proliferate very rapidly and become much more numerous 
 than the epithelial cells. The sex cords become more and more coiled during 
 development and anastomose with one another near the convex surface 
 of the testicle. Beginning after birth and continuing up to the time of 
 puberty, lumina appear in them by displacement of the central cells, and 
 
412 TEXT-BOOK OF EMBRYOLOGY. 
 
 they thus give rise to the convoluted seminiferous tubules. The supporting 
 cells (of Sertoli) are probably derived from the undifferentiated epithelial cells. 
 
 The details of the further development of the spermatogonia to form the 
 the spermatozoa have been described in the Chapter on Maturation. At this 
 point, that is, with the formation of the spermatozoon, the life cycle from a 
 mature male sexual element in an individual to a mature male sexual element 
 in an individual of the succeeding generation is completed. 
 
 The rete cords constitute an anastomosing network of solid cords of small, 
 darkly staining cells, situated in the hilus region. These cords later acquire 
 irregular lumina, which are lined with cuboidal cells, and form the rete testis. 
 Evaginations grow out from the rete and fuse with the ends of the convoluted 
 tubules, thus forming the straight tubules. On the other hand, outgrowths 
 from the rete unite with the tubules in the cephalic portion of the mesonephros, 
 so that a direct communication is established between the convoluted semi- 
 niferous tubules and the mesonephric tubules. There is thus formed the proxi- 
 mal part of the efferent duct system of the testicle (Fig. 365). That portion 
 of the tunica albuginea in which the rete testis lies, becomes somewhat thickened 
 to form the mediastinum testis. 
 
 The stroma of the testicle is derived for the most part from the mesenchyme 
 of the "indifferent" gland or genital ridge. Probably a smaller part is derived 
 from the germinal epithelium (see p. 404). During development, however, 
 the glandular elements increase more rapidly than the stroma, so that in the 
 adult they predominate. There is a tendency for the convoluted tubules to 
 become arranged in groups which are separated by trabeculae of connective 
 tissue radiating from the mediastinum. The interstitial cells of the stroma are 
 direct derivatives of the connective tissue cells (Fig. 370). 
 
 Determination of Sex. 
 
 The views regarding the determination of sex are discussed in the chapter 
 on Maturation (page 27) in connection with the question of Mendelian 
 heredity. 
 
THE DEVELOPMENT OF THE UROGEXITAL SYSTEM. 
 
 413 
 
 The Ducts of the Genital Glands and the Atrophy of the 
 Mesonephroi. 
 
 In the Female. Strictly speaking, the ovaries are ductless glands; for 
 neither developmentally nor anatomically are the ducts which convey their 
 specific secretion directly connected with them. Furthermore, these ducts are 
 in part transformed into certain organs for the reception and retention of both 
 kinds of sexual elements. In other words, the ducts in part become specially 
 modified to form the vagina and uterus, of which the latter serves as an organ 
 of maintenance for the embryos of the next generation. 
 
 The ducts originate in connection with the mesonephroi, and are known at 
 first as the Mullerian ducts. They appear in both sexes alike but persist only in 
 the female. In the lower Vertebrates they are split off from the mesonephric 
 ducts. In the higher forms, however, their mode of origin is not known with 
 
 Ureter 
 
 Intestine 
 
 Mesonephric duct 
 
 Liver. 
 
 Genital cord 
 
 Mullerian duct 
 
 Left umbilical artery 
 
 Bladder 
 
 Right umbilical artery 
 
 FIG. 371. From a transverse section through the pelvic region of a human embryo 
 of 25 mm. (82-9 weeks). Keibel. 
 
 certainty, but the present evidence favors the view that they arise independ- 
 ently of the mesonephric ducts. They appear in human embryos of 8-14 mm. 
 The mesothelium on the lateral surface of the cephalic end of each mesonephros 
 becomes thickened and then invaginates or dips into the underlying mesen- 
 chyme. By proliferation of the cells at its tip, the invaginated mass grows 
 caudally as a duct parallel with and close to the mesonephric duct. The two 
 ducts come to be embedded in a ridge which at the cephalic end of the meso- 
 nephros is situated laterally, but toward the caudal end bends around and comes 
 to lie ventrally. Beyond (caudal to) the mesonephros the ridge is attached to 
 the lateral body wall, and near the urogenital sinus it meets and fuses with its 
 fellow of the opposite side (Fig. 371). The two Mullerian ducts, contained 
 in the ridges, also approach each other and fuse. The fusion begins in 
 embryos of 25 to 28 mm. (end of second month), and about the same time they 
 open into the dorsal side of the urogenital sinus. The relations of the Mullerian 
 
414 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 and mesonephric ducts are different in different parts of their courses. At the 
 cephalic end the Miillerian lies dorsal to the mesonephric, but farther back it 
 runs more laterally, then ventrally, and finally opens into the urogenital sinus 
 on the medial side of the mesonephric duct. 
 
 THE OVIDUCT. The single part of each Mullerian duct gives rise to the 
 oviduct. The opening at the cephalic end remains as the ostium abdominale 
 tuba, which from the beginning communicates directly with the abdominal 
 cavity (coelom) and never becomes connected with the ovary (Fig. 366). The 
 rim of the opening sends from three to five projections into the abdominal 
 cavity to form the primary fimbrice. Secondary branches grow out from these 
 and form the numerous fimbriae of the adult oviduct. The part of each 
 
 Bladder 
 
 Uterus Rectum 
 
 Symphysis pubis 
 
 \\ ' ' - , .;:. 
 
 Cervix uteri 
 
 Labium majus I Hymen 
 
 Labium minus 
 
 Vagina 
 
 FIG. 372. Right half of the pelvic region of a female human foetus of 7 months. Nagel. 
 
 Miillerian duct between the fimbriated end and the fused caudal end, grows in 
 length as the embryo develops, but not proportionately, so that in the adult the 
 oviduct is relatively shorter than in the embryo. At first it is lined with simple 
 cylindrical epithelium, but later the cells become cuboidal, and during the 
 second half of f cetal life acquire distinct cilia. The connective tissue and muscle 
 of the oviduct are derived from the mesenchyme that primarily surrounds the 
 Mullerian duct. 
 
 In connection with one of the fimbrias of the oviduct there is sometimes found 
 a small vesicle lined with ciliated epithelium, forming the non-stalked hydatid 
 (of Morgagni), which possibly represents the extreme cephalic end of the 
 Miillerian duct (Fig. 380). In this case the permanent ostium of the tube 
 would be of secondary origin. 
 
THE DEVELOPMENT OF THE UROGENITAL SYSTEM. 415 
 
 THE UTERUS AND VAGINA. The fused caudal ends of the two Mullerian 
 ducts form the anlage of the uterus and vagina, which is a single medial tube 
 opening into the urogenital sinus (Fig. 363). During the third month certain 
 histological changes bring about a differentiation between the cephalic end or 
 uterus and the caudal end or vagina. The simple columnar epithelium of the 
 vaginal portion changes to stratified squamous, and during the fourth month 
 the lumen becomes closed. Near the external orifice a semicircular fold ap- 
 pears, which represents the hymen (Fig. 372). During the sixth month the 
 lumen reappears by a breaking down of the central cells. The epithelium of 
 the uterus, primarily high columnar, becomes lower and toward the end of 
 foetal life acquires cilia. Many irregular folds appear in the mucosa of the 
 vagina, a smaller number in the uterus (Fig. 372). Some of the folds in the 
 
 Ovary 
 
 Mesovarium 
 
 Broad ligament 
 with paroophoron 
 
 Oviduct 
 
 Mesosalpinx 
 with epoophoron 
 
 FIG. 373. Transverse section through the ovary and broad ligament of a human 
 foetus of 3 months. Nagel. 
 
 uterus constitute the regular plica palmatcz of the cervix. The uterine glands 
 represent evaginations from the epithelial lining. They do not begin to develop 
 until after birth (one to five years), and their development is usually not com- 
 pleted until the age of puberty. 
 
 The muscle and connective tissue of the walls of the uterus and vagina are 
 derived from the mesenchyme which surrounds the Mullerian ducts. The 
 muscle develops relatively late (after the fourth month of foetal life). 
 
 ATROPHY OF THE MESONEPHROI. By far the greater part of each meso- 
 nephros degenerates and disappears, and the parts that do persist are rudimentary 
 and possess no functional significance. The cephalic portion leaves ten to 
 twenty coiled tubules which terminate blindly at one end and at the other end 
 open into a common duct that represents the cephalic end of the mesonephric 
 duct. These tubules constitute the epoophoron (parovarium, organ of Rosen- 
 
416 TEXT-BOOK OF EMBRYOLOGY. 
 
 miiller) which comes to lie in the mesosalpinx between the oviduct and the 
 mesovarium, and later in the mesentery between the oviduct and the ovary 
 (Fig. 373). At the height of their development the tubules are lined with 
 columnar, ciliated epithelium. The rete cords of the ovary (rete ovarii, p. 407) 
 during their development unite with the tubules in the cephalic portion of the 
 mesonephros, but later disappear. The epoophoron is homologous with the 
 tubules of the head of the epididymis in the male. 
 
 The caudal portion of the mesonephros leaves a few tubular remnants 
 which come to lie in the broad ligament near the hilus of the ovary. These con- 
 stitute the paroophoron which is homologous with the paradidymis in the male 
 (Fig. 373). They may disappear before birth or may persist through life. 
 
 The mesonephric duct also leaves certain remnants which are situated (i) in 
 the broad ligament, (2) in the lateral wall of the uterus, (3) in the lateral wall of the 
 vagina, and (4) in the tissue lateral to the external genital opening. These rem- 
 nants are known as the canals of Gartner, and they naturally lie in the course of 
 the duct in the embryo. All the rudimentary structures derived from the 
 mesonephroi and their ducts are extremely variable. 
 
 In the Male. In the male all the efferent ducts of the genital glands, except 
 the rete testis, are derived from the mesonephroi and their ducts. As described 
 earlier in this chapter (p. 411), the rete testis acquires a connection with some of 
 the tubules in the cephalic end of the mesonephros and with the sex cords or 
 anlagen of the convoluted and straight seminiferous tubules (see Fig. 365). 
 This establishes a communication between the seminiferous tubules and the 
 tubules of the mesonephros. Those mesonephric tubules with which the rete 
 testis unites persist as the efferent ductules (or vasa eff erentia) . The latter form 
 a set of coiled ducts which are situated in the head of the epididymis and which 
 open into the cephalic part of the mesonephric duct (Fig. 347). They are 
 homologous with the epoophoron in the female. 
 
 The next succeeding portion of the mesonephric duct becomes the duct of the 
 epididymis which in its tortuous course constitutes the bulk of the body and tail 
 of the epididymis and passes over into the caudal portion of the mesonephric 
 duct. The latter portion becomes the deferent duct (vas def erens) . The caudal 
 end of the deferent duct forms the ejaculatory duct which opens into the urogeni- 
 tal sinus. The seminal vesicles appear during the third month as lateral 
 evaginations from the ejaculatory ducts. 
 
 The portions of the mesonephros not involved in the formation of the duct 
 system of the testicle atrophy and for the most part disappear. They leave 
 certain tubules, however, which persist as rudimentary structures connected 
 with the testicle. In the cephalic end, some of the tubules persist in part and 
 come to lie among the efferent ductules, being either attached to the latter or un- 
 connected, and forming the appendage of the epididymis. The caudal part of 
 
THE DEVELOPMENT OF THE UROGEXITAL SYSTEM. 
 
 417 
 
 the mesonephros leaves a few tubules which come to lie near the head of the epi- 
 didymis and form the paradidymis (or organ of Giraldes) , the tubules of which 
 are lined with columnar, ciliated epithelium. Near the transition from the 
 duct of the epididymis to the deferent duct there is almost invariably a tubule 
 (sometimes branched) which also represents a remnant of the mesonephros and 
 is known as the aberrant ductule. It usually opens into the duct of the epididy- 
 mis, but may lie free in the tissue around it (Fig. 347). 
 
 ATROPHY OF THE MULLERIAN DUCTS. These ducts persist in the female 
 and become the oviducts, uterus and vagina; in the male they degenerate and 
 disappear almost entirely. The degeneration begins about the time they open 
 
 Diaphragmatic 
 ligament of 
 mesonephros 
 
 Genital gland 
 
 Mesonephros 
 
 Mesonephric duct 
 
 Urachus 
 
 Mesonephric duct 
 
 Inguinal ligament 
 
 Umbilical artery 
 FIG. 374. Crogenital organs in a human embryo of 17 mm. (6 weeks). Kollmann's Atlas. 
 
 into the urogenital sinus (embryos of 25 to 28 mm.) ; by the time the embryo 
 reaches a length of 60 mm. only the extreme cephalic end and the caudal 
 third remain, and at 90 mm. the entire duct is gone except the extreme ends. 
 The cephalic end persists as the appendix testis (or hydatid of Morgagni) 
 (Figs. 347, 379). The caudal end persists as the utriculus prostaticus (uterus 
 masculinus). 
 
 Changes in the Positions of the Genital Glands and the Development 
 
 of their Ligaments. 
 
 During the early stages of development the genital glands testicles or 
 ovaries are situated far forward in the abdominal cavity. During the eighth 
 week they lie opposite the lumbar vertebrae. During the succeeding months, 
 up to the time of birth, they gradually move caudally to the positions they 
 
418 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 occupy in the adult. This migration is brought about, to some extent at 
 least, by the influence of certain bands of tissue which are primarily like 
 mesenteries. As the mesonephros develops and projects into the body cavity. 
 
 Ureter 
 
 Deferent duct 
 
 Inguinal ligament 
 (Gubernaculum testis) 
 
 Processus vaginalis 
 peritonasi 
 
 .--Umbilical cord 
 
 FIG. 375. From a dissection of the pelvic region of a male human foetus of 21 cm. 
 
 Kollmanri's Atlas. 
 
 it comes to be attached along the dorsal body wall, lateral to the dorsal mesen- 
 tery, by a sheet of tissue which is called the mesonephric mesentery. Cranial to 
 the mesonephros, this mesentery is continued as the diaphragmatic ligament 
 
 1>- Spermatic cord 
 
 A 
 
 ' \ 
 
 *n Inguinal ring 
 
 Tunica vaginalis 
 
 Tunica vaginalis 
 
 communis 
 
 Inguinal cone 
 
 Scrotum 
 
 Raphe* 
 
 FIG. 376. From a dissection of the scrotal region of a human foetus of 25 cm. 
 Kollmann's Atlas. 
 
 of the mesonephros, which as the name indicates, is attached to the diaphragm; 
 caudally it is continued to the inguinal region as the inguinal ligament of the 
 
THE DEVELOPMENT OF THE UROGENITAL SYSTEM. 
 
 419 
 
 mesonephros (Fig. 374). The genital gland lies on the medial side of the 
 mesonephros and is attached to the latter by a sort of mesentery which becomes 
 the mesovarium in the female or the mesorchium in the male. The cephalic 
 portions of the ducts (Miillerian and mesonephric) lie close together in a ridge 
 on the lateral surface of the mesonephros; as they pass caudally they extend 
 around to the ventral surface of the mesonephros and approach the medial line, 
 and finally, in the pelvic region, the two ridges meet and fuse, forming the so- 
 called genital cord (Fig. 371). The genital cord thus contains the mesonephric 
 and Mullerian ducts, the latter fusing to form a single tube (the anlage of the 
 uterus and vagina, p. 415). It also contains the umbilical arteries. 
 
 Kidney 
 
 Suprarenal gland 
 
 Intestine 
 
 Round ligament 
 ("Inguinal ligament) 
 
 Umbilical artery 
 
 Umbilical vein 
 
 FlG 377- From a dissection of the pelvic region of a female human foetus of 7.5 cm. 
 
 Kollmann's Atlas. 
 
 Such a condition is found in embryos of about eight weeks. From this 
 time on, the processes of development follow divergent lines in the two sexes, 
 the differences becoming more marked from month to month. Certain struc- 
 tures persist and other disappear, according to the sex. The mesenteries and 
 ligaments undergo metamorphoses and the genital glands migrate caudally. 
 
 Descent of the Testicles. As the mesonephros atrophies, its mesentery 
 and the mesentery of the testicle are combined to form a single band of tissue 
 which, of course, is continuous with the inguinal ligament. The latter now 
 becomes the so-called gubernaculum testis (Hunteri), a strong band or cord 
 composed of connective tissue and smooth muscle. Its cephalic end is attached 
 to the epididymis; its caudal end pierces the body wall in the inguinal region and 
 
420 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 is attached to the corium of the skin (Fig. 375). It plays an important part in 
 the descent of the testicle. The descent is brought about through the principle 
 of unequal growth. As the body grows in length, the gubernaculum grows 
 much less rapidly and, since the caudal end of the latter is fixed, the natural 
 result is the drawing downward of the testicle. This takes place gradually, 
 and at the end of the third month the testicle lies in the false pelvis ; at the end 
 of the sixth month close to the body wall at the inguinal ring. 
 
 During the third month a second factor in the descent of the testicle appears. 
 This is an evagination of the peritoneum at the point where the gubernaculum 
 pierces the body wall. The evagination at first is a shallow depression, known 
 
 Kidney 
 Mullerian duct 
 
 Genital gland 
 Mesonephros 
 
 Ureter 
 
 Inguinal ligament 
 
 Mesonephric duct 
 
 Mullerian duct 
 
 Apex of bladder 
 Bladder 
 Opening of ureter 
 
 Opening of mesonephric duct 
 
 Opening of Mullerian ducts 
 
 Rectum 
 
 Urogenital sinus 
 
 Cloaca 
 
 Genital tubercle 
 
 Genital ridge 
 
 Opening of cloaca 
 
 FIG. 378. Diagrammatic representation of the urogenital organs in the " indifferent " stage. Hertivig* 
 
 as the processus vaginalis peritonei, but continues to burrow through the body 
 wall and causes an elevation in the skin which is destined to become one side of 
 the scrotum (see p. 426) . The opening of the peritoneal sac into the body cavity 
 is the inguinal ring. In its descent the testicle passes through the inguinal ring 
 and comes to lie in the elevation in the skin or scrotum (ninth month) . Whether 
 its passage into the scrotum is the result of a traction by the gubernaculum is 
 not certain. The inguinal ring then closes by apposition of its walls and the 
 testicle lies in a closed sac which has been pinched off, so to speak, from the body 
 cavity (Fig. 376). 
 
THE DEVELOPMENT OF THE UROGENITAL SYSTEM. 
 
 421 
 
 Kidney 
 
 Appendage of testicle 
 (hydatid of Morgagm) 
 
 Epididymis 
 
 Testicle 
 
 Paradidymis 
 
 Deferent duct 
 
 Mullerian duct 
 
 Gubernaculum testis 
 
 Ureter 
 
 Seminal vesicle 
 Deferent duct 
 
 Epididymis 
 Testicle 
 
 Gubernaculum testis 
 
 Kidney 
 
 Hydatid 
 
 Oviduct 
 (fimbrise) 
 
 Epoophoron 
 Ovary 
 
 Paroophoron 
 
 Mesonephric duct 
 
 Oviduct 
 
 Epoophoron 
 
 Ovary 
 
 Ovarian ligament 
 
 Uterus 
 Round ligament 
 
 Vagina 
 
 Apex of bladder 
 
 Bladder 
 
 Opening of ureter 
 
 Urethra 
 
 Opening of ejacul. duct 
 
 Prostate 
 
 Urethra Sinus prostaticus 
 
 FIG. 379. 
 
 Apex of bladder 
 
 Urethra 
 Vestibulum vaginae 
 
 FlG. 380. 
 
 FIG. 379. Diagram of the development of the male genital organs from the 
 
 ;< indifferent " anlagen. Hertuuig. 
 FIG. 380. Diagram of the development of the female genital organs from the 
 
 " indifferent " anlagen. Hertwig. 
 
 These diagrams should be compared with Fig. 378. The dotted lines represent the organs in the 
 relative positions they occupy in the adult (with the exception of the Miillerian duct in the 
 male and the mesonephric duct in the female, which ducts disappear for the most part). 
 
422 TEXT-BOOK OF EMBRYOLOGY. 
 
 Since the testicle is invested by peritoneum from the beginning of its develop- 
 ment, it must be understood that in its passage into the scrotum it passes along 
 under the peritoneum. Consequently when it reaches the scrotum it is sur- 
 rounded by a double layer of peritoneum, the tunica vaginalis propria. 
 
 The descent of the testicle also produces marked changes in the course of 
 the deferent duct. Primarily the (mesonephric) duct extends cranially from 
 the urogenital sinus in a longitudinal direction. But as the testicle migrates, 
 the cephalic end of the duct is drawn caudally so that in the adult the deferent 
 duct extends cranially from the scrotum to the ventral side of the urinary 
 bladder and then bends caudally again to open into the urethra. 
 
 Descent of the Ovaries. The ovaries undergo a change of position cor- 
 responding to the descent of the testicles, although the change is not so extensive. 
 Primarily the Miillerian and mesonephric ducts lie in a ridge on the surface of 
 the mesonephros (p. 413). As the mesonephros and its duct atrophy, the Miil- 
 lerian duct (oviduct) comes to lie in a fold, the mesosalpinx, which is attached 
 to the mesovarium (Fig. 373) . At the same time the mesovarium becomes directly 
 continuous with and really a part of the inguinal ligament. The latter cor- 
 responds, of course, to the gubernaculum testis, and plays a role in the descent 
 of the ovaries. It may be conveniently divided into three parts, (i) a cephalic 
 part which is attached to the hilus of the ovary, (2) a middle part which ex- 
 tends from the ovary to the uterus, forming the ovarian ligament, and (3) a cau- 
 dal part which extends from the uterus to the inguinal region, forming the 
 round ligament of the uterus (Fig. 377). The round ligament pierces the body 
 wall and is attached to the corium of the skin. At the point where it passes 
 through the body wall there is a slight evagination of the peritoneum, the 
 diverticulum of Nuck, which corresponds to the processus vaginalis peritonei 
 in the male. 
 
 The ovaries gradually migrate caudally from their original position into the 
 false pelvis (third month) and thence into the true pelvis (at birth). Obviously 
 no traction can be exerted upon them by the round ligament (or caudal part of 
 the inguinal ligament), since the latter extends from the uterus to the inguinal 
 region. Their descent into the pelvic seems to be due to the unequal growth 
 of the ovarian ligaments, or in other words, to the fact that the ovarian liga- 
 ments grow proportionally less than the surrounding parts. During their 
 descent the ovaries become embedded in the broad ligaments of the uterus, 
 which represent further development of the peritoneal folds of the genital cord. 
 In this way the mesovarium becomes merged with the broad ligament. 
 
 On pages 420 and 421 are three diagrammatic representations of the changes 
 that take place in the genital systems of the two sexes. Fig. 378 represents 
 the " indifferent " stage in which all the embryonic structures are present; 
 Fig. 379 represents the changes that occur in the male; Fig. 380 represents the 
 
THE DEVELOPMENT OF THE UROGEXITAL SYSTEM. 
 
 423 
 
 changes that occur in the female. A careful study of the diagrams will assist 
 the student materially in understanding the processes of development which 
 have been described in the preceding paragraphs. 
 
 Below is a table that is meant to set forth briefly the various structures 
 which belong to the internal genital organs in the two sexes, and which are 
 derived from the structures in the "indifferent" stage. The words in italics 
 are the names of structures that persist in a rudimentary form. 
 
 Indifferent 
 
 Male 
 
 Female 
 
 
 
 
 
 Germinal epithelium (meso- 
 
 
 Convoluted seminiferous tubules 1 
 with spermatozoa / 
 
 Ovarian (Graafian) follicles 
 with ova. 
 
 Medullary cords 
 
 
 
 
 
 
 
 Straight seminiferous tubules . . 1 
 Rete testis j 
 
 Rete cords. 
 
 
 
 Part of stroma of testicle .... 
 
 Part of stroma of ovary. 
 
 f cephalic part 
 Mesonephros \ 
 [ caudal part < 
 
 r 
 
 i 
 
 i 
 
 Efferent ductules (vasa efferentia) \ 
 A ppendage of epididymis . . . J 
 Paradidymis (organ of Giraldes) \ 
 Aberrant ductules(vasa aberrantia) J 
 
 EpoopJioron, transverse duc- 
 tules. 
 
 Paroophoron. 
 
 
 
 Duct of epididymis (vas epididy- 
 midis) 
 
 Vesicular appendage (of 
 Morgagni} (?) 
 
 Mesonephric duct . . . . < 
 
 
 Deferent duct (vas deferens) . . 
 Ejaculatorv duct 
 
 Epoophoron, longitudinal 
 duct. 
 
 
 
 Seminal vesicle 
 
 Gartner's canals. 
 
 
 
 
 
 
 t 
 
 Morgagnfs appendage of testicle 1 
 (hydatid of Morgagni) . . . j 
 
 Fimbriae of oviduct 
 Oviduct. 
 
 
 . 
 
 Prostatic utricle (uterus masculinus) 
 
 Uterus. 
 Vagina. 
 
 Inguinal ligament of meso- " 
 nephros 
 
 \ 
 
 Gubernaculum testis (Hunteri) . . 
 
 k Ovarian ligament. 
 Round ligament of uterus. 
 
 
 
 
 
 
 
 Urethra ( prost ? ticpart ) 
 \ membranous part . . J 
 
 Prostate 
 
 f Urethra. 
 \ Vestibule of vagina. 
 Prostate. 
 
 
 
 Bulbo-urethral gland (Cowpers) 
 
 Larger vestib alar gland (Bar* 
 tholin's. 
 
 THE EXTERNAL GENITAL ORGANS. 
 
 In addition to the internal organs of generation, to which the description has 
 thus far been confined, certain other structures appear on the outside of the 
 body to form the external genitalia. In the case of these also there is an "indif- 
 ferent" stage from which the courses of development diverge in the two sexes. 
 
 During the sixth week a depression appearing on the ventral surface of the 
 caudal end of the body indicates the position of the cloacal membrane (p. 400). 
 This becomes surrounded by a slight elevation, produced by the thickening 
 of the mesoderm which is known as the genital ridge (Fig. 381). The cephalic 
 
424 TEXT-BOOK OF EMBRYOLOGY. 
 
 side of the ridge becomes raised still farther above the surface, forming a dis- 
 tinct protrusion, the genital tubercle. The tubercle continues to increase in 
 size, and the distal end forms a knob-like enlargement. Along the ventral (or 
 rather caudal) side a groove appears, which extends distally as far as the base 
 of the enlarged end. The ridges along the sides of the groove increase in 
 size and form the genital folds. In the meantime a second pair of elevations 
 appears lateral to the genital folds to form the genital swellings (Fig. 382). 
 
 After the cloacal membrane ruptures, a single opening is produced which 
 leads from the exterior into the cloaca. This opening is then separated by the 
 further growth of the urorectal fold (p. 400) into the opening of the urogenital 
 tract and the anal opening. The caudal part of the fold then enlarges to form 
 the perineal body, which serves to push the anus farther away from the genital 
 ridges. The latter, together with the genital tubercle and swellings, all of which 
 lie in the immediate vicinity of the urogenital opening, constitute the anlagen 
 of the external genital organs (Fig. 383). These at this time are in the 
 "indifferent" stage, from which development proceeds in one of two directions, 
 accordingly as the embryo is a male or a female. Up to the fourth month 
 there is little difference between the structures in the two sexes. After this the 
 differences become more and more obvious. 
 
 In the female the changes in the originally "indifferent" structures are 
 comparatively slight. The genital tubercle grows slowly and becomes the 
 clitoris. The enlarged extremity becomes more clearly marked off from the 
 other part to form the glans clitoridis. The skin covering the glans is converted 
 by a process of folding into a sort of prepuce. The genital folds, which 
 bound the opening of the urogenital tract, become elongated and form the 
 labia minora. The opening of the urogenital tract is the vestibulum vagina. 
 The genital swellings enlarge still more than the genital folds, by a deposition 
 of a considerable mass of fat in the mesenchyme, and become the labia majora. 
 The latter are the structures (mentioned on p. 420) which mark the points 
 at which the inguinal ligaments of the mesonephroi pierce the body wall, and 
 are homologous with the scrotum in the male (Figs. 384 and 385). 
 
 In the male the "indifferent" anlagen undergo more extensive changes 
 than in the female. The genital tubercle continues to grow more rapidly and 
 forms the penis, which is homologous with the clitoris. The enlarged extremity 
 becomes the glans penis, and an extensive folding of the skin over the glans 
 forms the prepuce. The groove on the caudal or lower side of the tubercle 
 elongates as the latter elongates and becomes deeper. Finally the ridge (or 
 genital fold) on each side of the groove meets and fuses with its fellow of the 
 opposite side, thus enclosing within the penis a canal the penile portion of 
 the urethra. The groove is primarily continuous with the opening of the uro- 
 genital tract, and as the fusion takes place the penile portion forms a direct 
 
Gen. r. 
 
 THE DEVELOPMENT OF THE UROGENITAL SYSTEM. 425 
 
 Umb. c. 
 
 ":< ..^ 
 
 ^ 
 
 -*.'. Umb. c. 
 
 Gen. tub. 
 
 do. and 
 gen. f. 
 
 GI. p. 
 
 FIG. 385. FIG. 386. 
 
 FIGS. 381-386. Stages in the development of the external genital organs. Kollmann's Atlas. 
 FIG. 381, " indifferent " stage embryo of 17 mm.; Fig. 382, " indifferent " stage embryo of 23 mm-; 
 
 Fig. 383, " indifferent " stage embryo of 29 mm. (beginning of 3d month); Fig. 384, female 
 
 embryo of 70 mm. (n weeks); Fig. 385, female embryo of 150 mm. (16 weeks); Fig. 386, 
 
 male embryo of 145 mm. (16 weeks). 
 An.y Anus; Cl., clitoris; Clo.and gen. /., cloaca and genital folds; CL m., cloacal membrane; Ext., 
 
 lower extremity; Gen. /., genital folds; Gen. r., genital ridge; Gen. yw., genital swelling; 
 
 Gen. tub., genital tubercle; Gl. p., glans penis; Lab. ma., labium majus; Lab. mi., labiura 
 
 minus; Ra., raphe of scrotum; Scr., scrotum; Ta., tail; Ug. s., urogenital sinus; Umb. c^ 
 
 umbilical cord. 
 
426 TEXT-BOOK OF EMBRYOLOGY. 
 
 continuation of the internal (membranous and prostatic) portion of the urethra. 
 The genital swellings also fuse and form the scrotum, the line of fusion in the 
 medial line becoming the raphe (Fig. 386). Primarily the inguinal ligaments 
 of the mesonephroi are attached to the corium of the skin in the genital swellings, 
 and as the testicles descend they pass through the inguinal ring into the scro- 
 tum. In a sense the scrotum represents an evagination of the body wall 
 
 THE DEVELOPMENT OF THE SUPRARENAL GLANDS. 
 
 Although the suprarenal glands do not logically come under the head of the 
 urogenital system, being neither functionally nor developmentally a part of the 
 latter, it is most convenient to consider them in this chapter. 
 
 In Mammals including man these glands are composed of two parts which 
 can be differentiated histologically and topographically the cortex and 
 medulla. The cortex is composed of trabeculae and spheroidal masses of cells 
 
 Phaeochrome cells 
 i 
 
 Nerve fibers 
 
 \ 
 
 Phaeochrome Connective Sympathetic 
 
 cells tissue ganglion cells 
 
 FIG. 387. Section of a sympathetic ganglion in the cceliac region of a frog (Rana esculenta), 
 showing differentiating phaeochrome cells. Giacomini. 
 
 which do not have a strong affinity for the ordinary cytoplasmic stains and 
 which contain granules of a fat-like substance known as lipoid granules. The 
 medulla is composed of irregularly arranged sympathetic ganglion cells and 
 other granular cells which, after treatment with chrome salts, acquire a peculiar 
 brownish color. The brown cells are known as chromaffin (or phaeochrome) 
 cells and their granules as chromaffin (or phaeochrome) granules. As cortex 
 and medulla are distinct anatomically, they are also distinct developmentally, 
 being derived from two distinct and different parent tissues which unite 
 secondarily. Furthermore, it is an interesting fact that in the lower Vertebrates 
 (Fishes) the two parts remain permanently separate; that in the ascending 
 scale of animal life (Amphibia, Reptiles, Birds) they become more closely 
 associated; and that finally (in Mammals) they unite to form a single glandular 
 structure. In Mammals the phylogenetic history is repeated with remarkable 
 
THE DEVELOPMENT OF THE UROGENITAL SYSTEM. 
 
 427 
 
 precision during the development of an individual : The two parts arise sepa- 
 rately, come closer together, and finally unite. 
 
 The Cortical Substance. The cortex is of mesothelial (mesodermal) 
 origin. In embryos of five to six mm. the mesothelium at the level of the 
 cephalic third of the mesonephros proliferates and sends buds or sprouts into 
 the mesenchyme at each side of the root of the dorsal mesentery. These 
 sprouts soon lose their connection with the parent mesothelium and unite with 
 one another to form a rather compact mass of epithelial-like cells ventro-lateral 
 to the aorta (Fig. 314). Frequently the two masses fuse across the medial line 
 ventral to the aorta. They constitute the anlagen of the cortical substance of 
 
 
 Connective tissue MS 
 
 Cortex 
 
 Medulla 
 (Phaeochrome cells) 
 
 FIG. 388. From a transverse section of a 40 mm. pig embryo, showing the growth of the medullary 
 substance into the cortical substance of the suprarenal gland. The vessel in the center of 
 the figure is the aorta. Wiesel. 
 
 the two suprarenal glands. From the fact that in the lower forms they remain 
 separate from the medullary substance and lie between the urinary organs, 
 they are known as the interrenal organs. 
 
 The Medullary Substance. A little later than the appearance of the 
 cortical anlage, the cells of some of the developing sympathetic ganglia become 
 differentiated into two types (i) the so-called sympathoblasts which develop into 
 sympathetic ganglion cells, and (2) ph&ochromoblasts which are destined to give 
 rise to the phceochome or chromafiin cells (Fig. 387). Hence the chromafrin 
 cells are derivatives of the ectoderm, since the ganglia are of ectodermal origin. 
 They soon become more or less separated from the ganglia, migrate to the 
 
428 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 region of the cortical anlagen and then penetrate the latter in cord-like masses 
 (Fig. 388) . Finally these masses unite in the interior of the cortical substance 
 to form a single compact mass (Fig. 389). Along with the phaeochrome masses, 
 sympathoblasts also are carried in and give rise to the sympathetic ganglion cells 
 within the gland. The two types of cells together constitute the medullary 
 substance. In the lower forms the phseochrome masses remain separate from 
 the cortical substance and are known as the suprarenal organs. In Mammals 
 the two sets of organs (interrenal and suprarenal) unite to form the suprarenal 
 gland. 
 
 |fe 
 
 ill 
 
 
 '> s -''-'# V : '.??V^v '*V 
 
 
 Med. Cor. Cor. 1 
 
 FIG. 389. Section of the suprarenal gland of a 119 mm. pig embryo. Cor., Cortex; Cor.*, some 
 cortical substance in the center of the gland; Med., medulla. Wiesel. 
 
 At the time when the mesonephros is fully developed, the cortical substance 
 forms a small oval body near its cephalic end. During the union of the cortex 
 and medulla and the atrophy of the mesonephros, the suprarenal gland becomes 
 more closely associated with the cephalic end of the kidney, and by the middle of 
 the third month has practically reached its adult position. During the third 
 month and the first half of the fourth month the glands increase in size and 
 become relatively large structures, larger in fact than the kidneys. From the 
 fourth month on, they grow proportionately less than the neighboring organs, 
 and by the sixth month are about half as large as the kidneys. At birth the 
 ratio of their weight to that of the kidneys is about 1:3; in the adult about i : 28. 
 
 While perhaps in a normal course of development all the anlagen are united 
 in the adult suprarenal gland, it is not unusual to find accessory structures in 
 various places. Some of these consist of cortical tissue only and are usually 
 
THE DEVELOPMENT OF THE UROGENITAL SYSTEM. 
 
 429 
 
 found in or near the capsule of the gland. Others may consist of both cortical 
 and medullary substances, and are found in the vicinity of or embedded in the 
 kidneys, in the retroperitoneal tissue near the kidneys, in the walls of neighbor- 
 ing blood vessels, or associated with the internal genital 
 organs in the rete testis or epididymis, or in the broad 
 ligament. These accessory structures may arise inde- 
 pendently of the main gland, or they may be portions of 
 the main gland which were separated during the union 
 of the different anlagen of the latter and were carried 
 away in the descent of the genital glands. 
 
 In addition to the chromamn tissue which enters into 
 the formation of the main gland or of accessory glands, 
 there are other small masses of this tissue which remain 
 permanently associated with some of the prevertebral 
 and peripheral sympathetic ganglia. 
 
 Recent researches have shown that the Carotid Skein 
 (glomus caroticum, intercarotid ganglion, carotid gland) , 
 which formerly was believed to be a derivative of the 
 epithelial lining of one of the branchial grooves, is of 
 sympathetic origin and that the cells acquire the charac- 
 teristic chromamn reaction. These facts indicate that 
 it is closely allied with the medullary substance of the suprarenal gland. 
 
 FIG. 390. Diagram of 
 the developing phoeo- 
 chrome masses in a 
 human foetus of 50 
 mm. A y Aorta; N, 
 cortical substance (in- 
 terrenal gland) ; U y 
 ureter; R, rectum. 
 Kohn. 
 
 Anomalies. 
 
 THE KIDNEYS. Rarely is there congenital absence of both kidneys. More 
 often there is a high degree of aplasia in both organs in otherwise well-developed 
 children. In either case death necessarily soon follows. Not infrequently one 
 kidney, usually the left, is poorly developed or absent and a compensatory 
 enlargement of the other exists. Such malformations are due to deficient 
 development of the organs, but the causes underlying the deficient development 
 are obscure. 
 
 One of the most common malformations is the abnormal position of one or 
 both kidneys (ectopia of the kidneys). Usually they occupy a position lower 
 than the normal in the abdominal cavity, which indicates that they have failed, 
 during development, to migrate forward to the normal limit (see p. 399). Very 
 rarely one or both organs migrate beyond the normal limit, in which case they 
 occupy positions cranial to the normal. 
 
 Not infrequently the lower ends of the two kidneys are fused across the 
 medial line, giving rise to the so-called "horseshoe kidney." Two renal 
 pelves and ureters are usually present. Occasionally the fusion is so extensive 
 
430 TEXT-BOOK OF EMBRYOLOGY. 
 
 that a single flat mass is formed. This occupies a medial position or lies at 
 either side of the medial line, and may be situated at the normal level or lower. 
 The renal pelvis may be single or double, with one or two ureters. In cases of 
 double ureters and pelves it seems most likely that the anlagen of the kidneys 
 have fused secondarily, that is, after the evagination from the mesonephric 
 ducts (p. 391). In cases where the pelvis and ureter are single, the fusion may 
 have occurred secondarily, although there is the possibility that only a single 
 anlage appeared. 
 
 Occasionally in children and even in adults the kidneys show a distinct 
 lobulation. This is due to the persistence of the lobulation that normally 
 exists in the foetus (p. 397). 
 
 The kidney may be more or less movable owing to laxity of the surrounding 
 tissue, or it may be floating, in which case it has a distinct mesentery. These 
 cases should be distinguished from those in which similar conditions have been 
 acquired, usually as the result of trauma. 
 
 Congenital cysts of the kidney are not uncommon. They vary in size and 
 number, sometimes being so numerous that they crowd out the greater part 
 of the renal tissue. Rarely they are so large and numerous that the affected 
 organ fills a large part of the abdominal cavity, resulting in serious or even 
 fatal disturbances of the functions of other organs. There are three views con- 
 cerning the origin of these cysts, (i) They may be the result of dilatation of 
 certain renal tubules derived from the nephrogenic tissue, which failed to unite 
 with the straight tubules (p. 393). (2) Inflammation in the medulla of the 
 foetal kidney may effect a closure of the lumina of some of the tubules, with 
 subsequent dilatation of the portions (tubules or renal corpuscles) that are cut 
 off from communication with the renal pelvis. (3) Normally some of the renal 
 corpuscles and tubules degenerate (p. 399) , and the cysts may arise as dilatations 
 of incompletely degenerated corpuscles or tubules or both. While these views 
 appear reasonable, none of them has been proven. All three views express 
 possibilities, and there is no good reason for believing that any one of them 
 expresses the only possibility. 
 
 THE URETERS. The renal pelvis is sometimes absent, the calyces uniting 
 to form two or more tubes which in turn unite to form the ureter. This prob- 
 ably is the result of abnormal branching of the ureter during development and 
 the failure of the ends of the branches to become dilated. Occasionally the 
 ureter is double or triple throughout the whole or a part of its length. The 
 most reasonable explanation of two or three complete ureters on either side is 
 that two or three separate evaginations arose from the mesonephric duct (p. 
 391.) Where the tube is double in only a part of its length, an abnormal 
 branching of the single original evagination is indicated. 
 
 Atresia of one or both ureters is occasionally met with. This probably 
 
THE DEVELOPMENT OF THE UROGENITAL SYSTEM. 431 
 
 represents a secondary constriction after the ureter is formed since both evag- 
 inations are hollow from the beginning (p. 391), but the cause of the constric- 
 tion is not understood. The atresia results in dilatation of the portion of the 
 ureter on the side toward the kidney. 
 
 Abnormal situations of the openings are sometimes seen, the explanation 
 of which is to be found in the relations of these tubes to the mesonephric ducts, 
 to the cloaca, and to the Miillerian ducts. In the male the ureters may open into 
 the seminal vesicles, the prostatic urethra, or the rectum. If one recalls that 
 the ureter arises as an evagination from the mesonephric duct near the opening 
 of the latter into the cloaca (p. 391), that the cloaca becomes separated into a 
 dorsal part (the rectum) and a ventral part (the urogenital sinus) (p. 400) , and 
 that the proximal end of the mesonephric duct is so far taken up into the wall 
 of the urogenital sinus (or bladder) that the ureter opens separately (p. 400), it is 
 readily seen that any interference with these normal processes of development 
 will result in abnormal opening of the ureter. If the ureter does not become 
 separated from the mesonephric duct, it will open into the deferent duct (vas 
 deferens), the latter being the proximal part of the mesonephric duct. And 
 since the seminal vesicle is an outgrowth from the proximal end of the meso- 
 nephric duct, the opening of the ureter is likely to be associated with the vesicle. 
 If the separation between the ureter and mesonephric duct is complete, but 
 the opening of the ureter does not migrate cranially on the wall of the bladder, 
 the opening comes to lie in the wall of the prostatic urethra. If the wall 
 (urorectal fold) separating the urogenital sinus and rectum is situated too far 
 dorsally, the opening of the ureter comes to be in the wall of the rectum. (Con- 
 sult Figs. 360, 361, 362, 363.) 
 
 In the female the ureters may open into the urethra, the vagina, or the uterus. 
 The explanation of the opening into the urethra is the same as in the male 
 (see preceding paragraph). The opening into the genital tract is probably to 
 be explained on the ground that the ureters fail to migrate cranially along 
 the wall of the urogenital sinus to the bladder, and as the fused ends of the 
 Miillerian ducts enlarge to form the uterus and vagina, the openings of the 
 ureters are taken up into their walls. 
 
 THE BLADDER. Absence of the bladder is very rare. Abnormal small- 
 ness, due to imperfect dilatation of the urogenital sinus (p. 401), is not infre- 
 quent. 
 
 The urachus, which represents the portion of the allantoic duct between 
 the bladder and the umbilicus (p. 401), not infrequently persists as a whole or 
 in part, giving rise to certain anomalous conditions in the region of the middle 
 umbilical ligament. The urachus may persist as a complete tube, lined 
 with epithelium, thus forming a means by which urine can escape at the 
 umbilicus. This condition is usually associated with obstruction of the 
 
432 TEXT-BOOK OF EMBRYOLOGY. 
 
 urethra and is known as uracho-vesical fistula. The urachus may degenerate 
 in part, leaving disconnected portions which frequently become dilated to 
 form cysts. 
 
 Vesical fissure, the most serious malformation of the bladder, is associated 
 with fissure of the lower abdominal wall. The edges of the cleft in the bladder 
 are continuous with those of the cleft in abdominal wall, the integument being 
 continuous with the lining of the bladder. In some cases the bladder is 
 everted through the cleft, and the cleft may even be so extensive as to involve 
 the external and internal genital organs. Vesical fissure is much more com- 
 mon in the male than in the female. No very satisfactory explanation of this 
 malformation has yet been given. It is in some way connected with imperfect 
 formation of the ventral abdominal wall resulting from influences acting at a 
 very early period of development. 
 
 THE URETHRA in both sexes may be abnormally small or abnormally large 
 or partly occluded, owing to faulty development of the urogenital sinus. In 
 the male the penile portion also maybe malformed, being represented merely 
 by a furrow on the lower side of the penis. This condition, known as hypo- 
 spadias, is due to the incomplete fusion or lack of fusion between the genital folds 
 along the lower side of the genital tubercle (p. 424) . In extreme cases the de- 
 fect may involve the scrotum and extend back as far as the prostate gland, the 
 two halves of the scrotum being separated. Epispadias, in which the urethral 
 cleft extends along the upper side of the penis (or the clitoris) is rare, and is 
 usually associated with vesico-abdominal fissure. Its mode of origin is not 
 understood. 
 
 THE TESTICLES. One of the most common malformations affecting the 
 male genital glands is the condition known as chryptorchism, in which the 
 glands, instead of descending into the scrotum, are retained within the ab- 
 dominal cavity. One or both testicles may be affected. They may occupy 
 their original position far forward in the abdominal cavity or may be situated 
 near the inguinal canal, or may lie at some intermediate point. The malposi- 
 tion is due to a failure in the normal descent into the scrotum (p. 419). The 
 cause of the failure is obscure. Not infrequently the ectopic testicles atrophy 
 or fail to develop properly at puberty. 
 
 Congenital absence of one or both testicles is rare. More frequently the 
 gland or efferent system of ducts is defective in part, owing to imperfect 
 development. In case of absence of the testicles the individual is small and 
 poorly developed ; when the glands are imperfectly developed the individual is 
 effeminate. 
 
 Cysts which are sometimes met with in the epididymis are possibly due to 
 dilatation of incompletely degenerated portions of the mesonephric tubules 
 or Miillerian ducts. Teratoid tumors and chorio-epitheliomata are occasionally 
 
THE DEVELOPMENT OF THE UROGENITAL SYSTEM. 433 
 
 found in the testicle. For a further discussion of these see chapter on Terato- 
 genesis (XIX). 
 
 THE OVARIES. Congenital absence of both ovaries is rare; defective 
 development of one is more common. Either anomaly may occur with or 
 without defects in the other genital organs. Occasionally the ovaries remain 
 rudimentary, their function as egg-producing organs never being assumed. 
 Malpositions, due to partial or complete failure in the normal descent into 
 the pelvis (p. 422), are not infrequent. Sometimes, on the other hand, they 
 descend to the inguinal canal and may even pass through the latter into the 
 labia majora. 
 
 Ovarian cysts occur frequently. Some of these (follicular cysts) may arise 
 during postnatal life as dilatations of Graafian follicles. Others probably 
 arise during foetal life in the same manner. Certain other forms of ovarian 
 tumors, known as cystadenomata, are possibly to be considered as derivatives 
 of the epithelium of the medullary cords which in normal cases disappear 
 entirely (p. 407; also Fig. 366). A discussion of the origin of teratoid tumors of 
 the ovary will be found in the chapter on Teratogenesis (XIX). 
 
 THE OVIDUCTS, UTERUS AND VAGINA. Absence of the oviducts is usually 
 associated with malformations of other parts of the genital tract. On the other 
 hand, normal oviducts may be present in conjunction with defective uterus 
 and vagina. Atresia may occur at the uterine or fimbriated end, or at any 
 intermediate point. 
 
 The majority of the malformations of the uterus and vagina can be at- 
 tributed to defective processes of development in the caudal ends of the Miiller- 
 ian ducts. It will be remembered that the caudal ends of these ducts normally 
 fuse to form a single medial tube which opens into the urogenital sinus, and 
 which constitutes the anlage of the uterus and vagina (p. 415; Fig. 363). It is 
 obvious that any defect in this fusion will result in some degree of duplicity 
 in the two organs in question. The fusion may be almost complete, the result- 
 ing abnormality being merely a small pocket which forms, at each side of the 
 fundus, a continuation of the cavity of the uterus. There may be a greater 
 degree of imperfection in the fusion, resulting in a partial division of the uterus 
 into two horns bicornuate uterus. The wall between the two Miillerian ducts 
 may remain patent in the entire uterine portion of the tract, thus giving rise 
 to a bipartite uterus. If the wall between the ducts remains intact throughout 
 both uterine and vaginal portions, the result is a complete division of the utero- 
 vaginal tract uterus didelphys. Occasionally the uterine portion of one 
 Miillerian duct may fail to develop properly and becomes a solid cord, resulting 
 in an unicornuate uterus. 
 
 Not infrequently the uterus remains rudimentary infantile uterus. This 
 anomaly is usually accompanied by stenosis of the vagina. Stenosis or other 
 
434 TEXT-BOOK OF EMBRYOLOGY. 
 
 defects in the vagina may occur, however, when the uterus is normal. In rare 
 instances the hymen is absent; in other cases it closes the entrance to the vagina 
 a condition known as imperf orate hymen. 
 
 Malformations of the uterus and vagina resulting from persistence of the 
 cloaca and atresia of the anus are mentioned on page 357. 
 
 HERMAPHRODITISM. 
 
 This condition implies a combination of the male and female sexual organs 
 in one individual, accompanied by a blending oi the general characteristics of 
 the two sexes When such an individual possesses both ovary and testicle, the 
 condition is known as true hermaphroditism; when the individual possesses 
 ovaries or testicles, the condition is known as false hermaphroditism. 
 
 TRUE HERMAPHRODITISM. The presence of both ovary and testicle in one 
 individual is one of the rarest anomalies in man. Furthermore, one or both of 
 the organs are sexually immature. Three forms can be recognized (Klebs) : 
 
 1. Lateral hermaphroditism, in which an ovary is present on one side and a 
 testicle on the other; 
 
 2. Unilateral hermaphroditism, in which both ovary and testicle are present 
 on one side, either ovary or testicle, or neither, on the other side; 
 
 3. Bilateral hermaphroditism, in which both ovary and testicle are present on 
 both sides. 
 
 In all these cases the general character of the body is of an intermediate 
 type, sometimes tending toward the male, sometimes toward the female. The 
 external genitalia are also of an intermediate type, with hypospadias, small 
 penis, separate scrotal halves, and small vaginal orifice. The uterus usually 
 shows some degree of duplicity. 
 
 FALSE HERMAPHRODITISM. In this type of hermaphroditism, in which 
 either ovaries or testicles are present in an individual with mixed general 
 sexual characteristics, two varieties can be recognized : 
 
 1. Masculine false hermaphroditism, the more common, in which testicles are 
 present but the external genitalia and general character of the body approximate 
 the female; 
 
 2. Feminine false hermaphroditism, in which ovaries are present but other- 
 wise male characteristics predominate. 
 
 The causes underlying the origin of hermaphroditism are among the most 
 obscure in teratogenesis. It is well known that up to the fourth or fifth week 
 the anlagen of the sexual glands are histologically "indifferent," and later be- 
 come differentiated into ovaries or testicles (p. 405). Since the secondary 
 sexual characteristics are dependent upon the development of the primary, they 
 also are brought out later. If the " indifferent " glands give rise to both ovaries 
 
THE DEVELOPMENT OF THE UROGENITAL SYSTEM. 435 
 
 and testicles, true hermaphroditism is the result; if they give rise to either 
 ovaries or testicles but the external genitalia and general characteristics develop 
 in the opposite direction, false hermaphroditism is the result. Thus the her- 
 maphroditic condition is potentially present in every individual during the 
 earlier stages of development; the most remarkable fact is that it is not more 
 common. 
 
 Recent researches in cytology have added a new phase to the question of the 
 origin of hermaphroditism. Accessory chromosomes have been demonstrated 
 in the ova and spermatozoa of many species of insects (McClung, Wilson, 
 Morgan) and in ova and pollen of dioecious plants (Correns). It has been 
 suggested that these have some significance in the determination of sex, the 
 female elements containing the additional chromatin elements (see p. 27). 
 Carrying this a step further, Adami has suggested that " hermaphroditism is 
 based upon aberration in the distribution of the chromosomes in either the ovum, 
 or the spermatozoon." 
 
 References for Further Study. 
 
 ADAMI, J. G.: The Principles of Pathology. Vol. I, 1908. 
 
 AICHEL, O.: Vergleichende Entwickelungsgeschichte und Stammesgeschichte der 
 Nebennieren. Arch. f. mik. Anat.. Bd. LVL, 190x5. 
 
 ALLEN, B. M.: The Embryonic Development of the Ovary and Testis in Mammals. 
 Am. Jour, of Anat., Vol. Ill, 1904. 
 
 BEARD, J.: The Germ-cells of Prisdurus. Anat. Anz., Bd. XXI, 1902. 
 
 BEARD, J.: The Morphological Continuity of the Germ Cells in Raja batis. Anat. Anz., 
 Bd. XVIII, 1900. 
 
 BONNET, R.: Lehrbuch der Entwickelungsgeschichte. Berlin, 1907. 
 
 EIGENMANN, C. H.: On the Precocious Segregation of the Sex-cells of Micrometrus 
 aggregatus. Jour of Morphol., Vol. V, 1891. 
 
 FELIX, W.: Entwickelungsgeschichte des Excretions-systems. Ergebnisse der Anat. 
 u. Entwick., Bd. XIII, 1903. 
 
 FELIX, W., and BUHLER^ A.: Die Entwickelung der Harn- und Geschlechtsorgane. In 
 Hert wig's Handbuch d. vergleich. u. experiment. Entwickelungslehre der Wirbeltiere, Bd. III. 
 Teil I, 1904. 
 
 GAGE, S. P.: A Three Weeks' Human Embryo, with Especial Reference to the Brain and 
 Nephric System. Am. Jour, of Anat., Vol. IV, 1905. 
 
 GERHARDT, U.: Zur Entwickelung der bleibenden Nieren. Arch. f. mik. Anat , Bd 
 ILVII, 1901 
 
 HERTWIG, O.: Lehrbuch der Entwickelungsgeschichte des Menschen und der Wirbel- 
 tiere. Jena, 1906. 
 
 HILL, E. C.: On the Gross Development and Vascularization of the Testis. Am. 
 Jour. of. Anat., Vol. VI, 1907. 
 
 HUBER, G. C.: On the Development and Shape of the Uriniferous Tubules of Certain 
 of the Higher Mammals. Am. Jour, of Anat., Vol. IV, Suppl., 1905. 
 
 KEIBEL, F.: Zur Entwickelungsgeschichte des menschlichen Urogenitalapparatus. 
 Arch.f. Anat. u. Physiol., Anat. Abth. y 1896. 
 
 KOHN, A.: Das chromaffine Gewebe. Ergebnisse der Anat. u. Entwick., Bd. XII, 1903, 
 
436 TEXT-BOOK OF EMBRYOLOGY. 
 
 KOLLMAX, J.: Lehrbuch der Entwickelungsgeschichte des Menschen. Jena, 1898. 
 
 KOLLMAX J.: Handatlas der Entwickelungsgeschichte des Menschen. Jena, 1907, 
 Bd. II. 
 
 M\RCHAXD, F.: Missbildungen. In Eulenburg's Real-Encyclopadie der gesammten 
 Heilkunde, Bd. XV, 1897. 
 
 McMuRRiCH, J. P.: The Development of the Human Body. Philadelphia, 1907. 
 
 MIXOT, C. S.: Laboratory Text-book of Embryology. Philadelphia, 1903. 
 
 MORGAN, T. H.: The Cause of Gynandromorphism in Insects. Am. Xaturalist, Vol. 
 XLI, 1907. 
 
 NAGEL, W.: Ueber die Entwickelung des Urogenitalsystems des Menschen. Arch. f. 
 Mik. Anal., Bd. XXXIV, 1889. 
 
 NAGEL, W.: Ueber die Entwickelung der Urethra und des Dammes beim Menschen. 
 Arch.f. mik. Anat., Bd. XL, 1892. 
 
 XAGEL, W.: U/eber die Entwickelung des Uterus und der Vagina beim Menschen. Arch. 
 f. mik. Anat., Bd. XXXVII, 1891. 
 
 PIERSOL, G. A. : Teratology. In Wood's Reference Handbook of the Medical Sciences, 
 Vol. VII, 1904. 
 
 POLL, H.: Die Entwickelung der Xebennierensysteme. In Hertwig's Handbuch der 
 vergleich. u. experiment. Entwickelungslehre der Wirbeltiere, Bd. Ill, Teil I, 1905. 
 
 RABL, C.: Ueber die Entwickelung des Urogenitalsystems der Selachier. MarpJwl. 
 Jahrbuch, Bd. XXFV, 1896. Theorie des Mesoderms. Ueber die erste Entwickelung der 
 Keimdruse. Morphol. Jahrbuch, Bd. XXTV, 1896. 
 
 SCHREIXER, H. E.: Ueber die Entwickelung der Amniotenniere. Zeitschr.f. ivissensch. 
 Zoologie, Bd. LXXI, 1902. 
 
 SOULIE, A.: Sur le mecham'sme de la migration des testicules. Com p. Rend, de la Soc. 
 de Biol., Paris, Ser. 10, T. II, 1895. 
 
 SOULIE, A.: Recherches sur le developpement des capsules surrenales chez les vertebres 
 superieurs. Jour. de. FAnat. et de la Physiol., T. XXXIX, 1903. 
 
 STOERK, O.: Beitrag zur Kenntnis des Aufbaus der menschlichen Xiere. Anat. 
 Hefte, Bd. XXIII, 1904. 
 
 TAXDLER, J.: Ueber Vornieren-Rudimente beim menschlichen Embryo. Anat. HefU^ 
 Bd. XXVIII, 1905. 
 
 TAUSSIG, F. J.: The Development of the Hymen. Am. Jour, of Anat., Vol. VIII, 1908. 
 
 WLESEL, J.: Ueber die Entwickelung der Xebennieren des Schweins, besonders der 
 Marksubstanz. Anat. Hefte, Bd. XVI, 1900. 
 
 WLXTWARTER, H.: Recherches sur Povogenese et Porganogenese de Povaire des Mammi- 
 feres. Arch, de Biol., T. XVII, 1900. 
 
 WOODS, F. W.: Origin and Migration of the Germ-cells in Acanthias. Am. Jour, of 
 Anal., Vol. I, No. 3, 1902. 
 
CHAPTER XVI. 
 THE DEVELOPMENT OF THE IHTEGUMENTARY SYSTEM. 
 
 The integument consists of the skin and certain accessory structures. The 
 skin is composed of the dermis (or corium) and the epidermis. The accessory 
 structures comprise the hairs, nails, sudoriferous glands, sebaceous glands, and 
 mammary glands. The epidermis (or epithelial layer) and all the accessory 
 structures are derived from the ectoderm; the dermis is mesodermal in its 
 origin. Other appendages of the skin such as scales, feathers, claws, hoofs, 
 and horns which are found only in the lower animals, are ectodermal 
 derivatives and belong in the same class as the accessory structures in man. 
 
 The Skin. 
 
 THE EPIDERMIS. The embryonic ectoderm consists primarily of a single 
 layer of cells (Fig. 81). During the latter part of the first month, the single 
 layer gives rise to two layers, of which the outer is composed of irregular flat 
 cells and is known as the epitrichium or periderm, the inner or basal, of larger 
 cuboidal cells which are the progenitors of the epidermal cells and of the acces- 
 sory structures. The epitrichial cells later become dome-shaped and acquire 
 a vesicular structure,' the nuclei becoming less distinct. They persist until the 
 middle of foetal life and are then cast off and mingle with the secretion of the 
 
 ly formed sebaceous glands as a constituent of the vernix caseosa (see p. 442) . 
 The epidermal cells, constantly increasing in number, soon come to form several 
 layers (4 to 6 in the sixth month). The innermost layer rests upon the base- 
 ment membrane and is composed of cuboidal or columnar cells rich in cytoplasm ; 
 the outer layers consist of irregular cells with clearer contents and less distinct 
 nuclei. 
 
 As development proceeds, the basal layer gives rise to several layers which 
 together constitute the stratum germinativum. The cells of the innermost 
 layers are constantly proliferating and thus forming new cells which are pushed 
 toward the surface. During the seventh month keratohyalin granules appear 
 in two or three layers which are then known collectively as the stratum granu- 
 losum. The clearer cells of the superficial layers undergo a process of de- 
 generation by which their contents are transformed into a horny substance, 
 the nuclei becoming fainter and finally disappearing. These modified or degen- 
 erated cells, which are constantly being cast off and replaced by others from 
 
 437 
 
438 TEXT-BOOK OF EMBRYOLOGY. 
 
 the deeper layers, constitute the stratum corneum (Fig. 392). In the thick 
 epidermis, on the palms of the hands and the soles of the feet, for example, a 
 few layers of cells just outside of the stratum granulosum become specially 
 modified (keratinized) to form the stratum lucidum. 
 
 THE DERMIS. In the first month the dermis is represented by closely ar- 
 ranged, spindle-shaped mesenchymal (mesodermal) cells underlying the 
 epidermis, and is separated from the latter by a delicate basement membrane. 
 This mesenchymal tissue gives rise to fibrous connective tissue which, about 
 the third month, becomes differentiated into two layers the dermis proper 
 and the deeper subcutaneous tissue. The papillae develop as little projections 
 of the dermis which grow into the stratum germinativum of the epidermis. 
 In some of these, many blood vessels appear, while in others nerve endings 
 
 Eponychium 
 Root of nail Nail 
 
 Sole plate 
 
 Phalanx II 
 
 Sweat glands 
 
 FIG. 391. Longitudinal section through the end of the middle finger of a 
 5 months human foetus. Bonnet. 
 
 (tactile corpuscles of Meissner) develop, thus giving rise to vascular and nerve 
 papillae. Usually a considerable amount of fat develops in the subcutaneous 
 tissue. Some of the mesencnymal cells of the dermis are transformed into 
 smooth muscle cells which are found in connection with the hairs (arrectores 
 pilorum), in the scrotum (tunica dartos), and in the nipples. 
 
 The dermis has generally been considered as a derivative of the cutis plates 
 (p. 163) which, with the myotomes, constitute the outer walls of the primitive 
 segments, but it is probable that the outer walls of the segments are trans- 
 formed wholly into muscle tissue (McMurrich). 
 
 The pigment in the dermis develops in the form of granules in the connect- 
 ive tissue cells; that in the epidermis appears as granules in the cells of the deeper 
 layers (white races) or of all the layers (dark races). Whether the pigment in 
 the epidermis arises independently or is carried from the dermis by wandering 
 cells is not known. 
 
THE DEVELOPMENT OF THE INTEGUMENTARY SYSTEM. 439 
 
 The Nails. 
 
 The nails are derivatives of the epidermal layer of the ectoderm, and cor- 
 respond morphologically to the claws and hoofs of lower animals. The 
 epidermis on the end of each finger and toe forms a thickening, known as the 
 primitive nail, which is encircled by a faint groove (Zander). This occurs 
 about the ninth week. Later the nail area migrates to the dorsal side of the 
 digit and becomes somewhat sunken below the surface of the surrounding 
 epithelium (Fig. 391). These observations have led to the conclusion that 
 primarily the nails in man occupied positions on the ends of the digits, cor- 
 responding to the positions of the claws in low r er forms. Furthermore, the fact 
 that the nails (or their anlagen) are at first situated on the ends of the digits and 
 subsequently migrate dorsally would exolain the innervation of the nail region 
 by the palmar (and plantar) nerves. 
 
 Strat. corneum "I 
 
 1 Epidermis 
 
 #> " I Strat. germinativum J 
 
 /.-*I^ 
 
 V-V **: 
 
 *i I SfSP@f- HairBerm 
 
 (*' Hf Hair papa 
 
 
 papilla 
 
 _- i--,.^ , w.w - , 
 
 Con. tis. follicle 
 
 Hair germ 
 
 Hair papilla Connective tissue 
 
 follicle 
 
 FIG. 392. Vertical section of the skin of a mouse embryo of 18 mm., showing 
 early hair germs. Maurer. 
 
 After the dorsal migration of the nail area, the epithelium and dermis along 
 the proximal and lateral edges become still more elevated to form the nail wall, 
 the furrow between the latter and the nail being the nail groove. At the distal 
 edge of the nail area, the epithelium becomes thickened to form the so-called 
 sole plate, which is probably homologous with the more highly developed sole 
 plate in animals with hoofs or claws. The epithelium of the nail area increases 
 in thickness, and, as in the skin, becomes differentiated into three layers 
 (Fig. 391). The outer layers of cells become transformed into the stratum 
 corneum. The cells of the next deeper layers, which acquire keratin granules 
 and constitute the stratum lucidum, degenerate and give rise to the nail sub- 
 stance. Thus the nail is a modified portion of the stratum lucidum. The 
 layers of epithelium beneath the nail form the stratum germinativum, which, 
 with the subjacent dermis, is thrown into longitudinal ridges. 
 
440 TEXT-BOOK OF EMBRYOLOGY. 
 
 After its first formation, the nail is covered by the stratum corneum and 
 the epitrichium, the two together forming the eponychium. The epitrichium 
 soon disappears; later the stratum corneum also disappears with the exception 
 of a narrow band along the base of the nail. 
 
 The formation of nail substance begins during the third or fourth month in 
 the proximal part of the nail area. The nail grows from the root and from the 
 under surface in the region marked by the whitish color (the lumda). New 
 keratinized cells are added from the subjacent stratum germinativum and be- 
 come degenerated to form new nail substance which takes the place of the old as 
 the latter grows distally. 
 
 The Hair. 
 
 The hairs, like the nails, are derivatives of the epidermal layer of the ecto- 
 derm. In embryos of about three months, local thickenings of the epidermis 
 appear (beginning in the region of the forehead and eye-brows) and grow 
 obliquely into the underlying dermis in the form of solid buds the hair germs 
 (Fig. 393, I, II). As the buds continue to elongate they become club-shaped 
 and the epithelium at the end of each molds itself over a little portion of the 
 dermis in which the cells have become more numerous and which is known as 
 the hair papilla (Fig. 392). 
 
 As the epidermal bud grows deeper, its central cells become spindle-shaped 
 and undergo keratinization to form the beginning of the hair shaft; the peripheral 
 layers constitute the anlage of the root sheath (Fig. 393, III, IV). The hair 
 shaft grows from its basal end, new keratinized cells being added from the 
 epithelium nearest the papilla as the older cells are pushed toward the surface 
 of the skin. The surface cells of the hair shaft become flattened to form the 
 cuticle of the hair (Fig. 393, V). The hairs appear above the surface about the 
 fifth month. Of the cells of the root sheath, those nearest the hair become 
 scale-like to form the cuticle of the root sheath; the next few layers become 
 modified (keratinized) to form Huxley's and Henle's layers. Outside of these 
 is the stratum germinativum, the basal layer of which is composed of columnar 
 cells resting upon a distinct basement membrane. The stratum germinativum 
 is continued over the tip of the papilla, where its cells give rise to new cells for 
 the hair shaft (Fig. 393, V). 
 
 The connective tissue around the root sheath becomes differentiated into an 
 inner highly vascular layer, the fibers of which run circularly, and an outer 
 layer, the fibers of which extend along the sheath. The two layers together con- 
 stitute the connective tissue follicle. 
 
 The first formed hairs, which are exceedingly fine and silky, develop in vast 
 numbers over the surface of the embryonic body and are known collectively as 
 the lanugo. This growth is lost (beginning before birth and continuing during 
 
THE DEVELOPMENT OF THE INTEGUMENTARY SYSTEM. 
 
 441 
 
 the first and second years after), except over the face, and is replaced by coarser 
 hairs. These in turn are constantly being shed during the life of the individual 
 
 t 
 
 
 
 \ ^m^7 MM 
 
 \^^p^r ^m 
 
 l s^*&* i 
 
 >V f tr<-2&? : ***f& '<< 
 
 ^ ft 
 
 FIG. 393. Five stages in the development of a human hair. 
 C, Papilla; 5, arrector pili muscle; c, beginning of hair shaft; d, point where hair shaft grows 
 through epidermis; e, anlage of sebaceous gland; /, hair germ; g, hair shaft; h, Henle's 
 layer; , Huxley's layer; k, cuticle of root sheath; /, inner root sheath; m, outer root sheath 
 in tangential section; n, outer root sheath; o, connective tissue follicle. 
 
 and replaced by new ones. The new hairs probably in most cases develop from 
 the old follicles, the cells over the old papillae proliferating and the newly 
 
442 TEXT-BOOK OF EMBRYOLOGY. 
 
 formed hairs growing up through the old sheaths. In some cases, however, new 
 follicles are formed directly from the epidermis and dermis. In some of the 
 lower Mammals, new hair germs appear as outgrows from the sheaths of old 
 follicles, thus giving rise to tufts of hair. The arrectores pilorum muscles arise 
 from the dermal (mesenchymal) cells and become attached to the follicles below 
 the sebaceous glands. 
 
 The Glands of the Skin. 
 
 THE SEBACEOUS GLANDS. These structures usually develop in connection 
 with hairs. From the root sheath a solid bud of cells grows out into the dermis 
 (Fig. 393, IV) and becomes lobed. The central cells of the mass undergo fatty 
 degeneration and the products of degeneration pass to the surface of the skin 
 through the space between the hair and its root sheath. The more peripheral 
 cells proliferate and give rise to new central cells which in turn are transformed 
 into the specific secretion of the gland, the whole process being continuous. On 
 the margins of the lips, on the labia minora and on the glans penis and prepuce, 
 glands similar in character to the sebaceous glands arise directly from the 
 epidermis independently of hairs. 
 
 THE SUDORIFEROUS GLANDS. The sweat glands begin to develop during 
 the fifth month as solid cylindrical growths from the deeper layers of the epider- 
 mis into the dermis (Fig. 391). Later the deeper ends of the cylinders become 
 coiled and lumina appear. The lumina do not at first open upon the surface 
 but gradually approach it as the deeper epidermal layers replace the more 
 superficial. 
 
 THE VERNIX CASEOSA. During fcetal life the secretion of the sebaceous 
 glands becomes mingled with the cast-off epitrichial and epidermal cells to form 
 the whitish oleaginous substance (sometimes called the smegma embryonum) 
 that covers the skin of the new-born child. It is collected especially in the 
 axilla, groin and folds of the neck. 
 
 THE MAMMARY GLANDS. 
 
 In embryos of six to seven mm., or even less, a thickening of the epidermis 
 occurs in a narrow zone along the ventro-lateral surface of the body (Strahl). 
 In embryos of 1 5 mm. this thickening, known as the milk ridge, extends from the 
 upper extremity to the inguinal region (Kallius, Schmidt). Later the caudal 
 end of the ridge disappears, while the cephalic portion becomes more prominent. 
 The further history of the ridge has not been traced, but in embryos considerably 
 older the anlage of each gland is a circular thickening of the epidermis in the 
 thoracic region, projecting into the underlying dermis. It seems most probable 
 that this local thickening represents a portion of the original ridge, the remainder 
 
THE DEVELOPMENT OF THE INTEGUMENTARY SYSTEM. 443 
 
 having disappeared. Later the central cells of the epidermal mass become 
 cornified and are cast off, leaving a depression in the skin (Fig. 394). In em- 
 bryos of 250 mm. a number of Solid secondary buds have grown out (Fig. 395). 
 These resemble the anlagen of the sweat glands, to which they are generally 
 considered as closely allied (Hertwig, Wiedersheim and others), and represent 
 the excretory ducts. Continued evaginations from the terminal parts of the 
 excretory ducts form the lobular ducts and acini. The acini, however, are 
 scarcely demonstrable in the male, and not even in the female until pregnancy. 
 Lumina appear by a separation and breaking down of the central cells of the 
 ducts and acini, the peripheral cells remaining as their lining. 
 
 Nipple 
 Epitrichium depression Dermis 
 
 Stratum 
 germinativura 
 
 Dermis 
 (Areolar zone) 
 
 Vv v:.v -. ' ^ ?5a ! S3?sgES#S - * ' " 
 
 FIG. 394. Vertical section through the anlage of the mammary gland of 
 a human foetus of 16 cm. Bonnet. 
 
 Late in foetal life, or sometimes after birth, the original depressed gland 
 area becomes elevated above the surface to form the nipple. The excretory 
 ducts (15 to 20 in number) which at first opened into the depression, thus come 
 to open on the surface of the nipple. In the area around the nipple the 
 areola numerous sudoriferous and sebaceous glands develop, some of which 
 come to open into the lacteal ducts. Sometimes rudimentary hairs appear. 
 Other glands known as areolar glands (of Montgomery) resembling rudi- 
 mentary mammary glands also develop from the epidermis of the areola. 
 
 After birth the mammary glands continue to grow slowly in both sexes up to 
 the time of puberty. After this they cease to grow in the male, and then atrophy. 
 In the female, growth of the glandular elements goes on, but very slowly, and 
 usually a considerable amount of fat develops in the surrounding tissue, 
 causing the enlargement of the breasts. 
 
 The Mammary Glands of Pregnancy. Even in the female, as stated before, 
 acini are scarcely demonstrable until pregnancy. The mamma consists 
 
444 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 mostly of connective tissue and fat, with scattered groups of duct-like tubules. 
 During pregnancy the tubules give rise to the acini by a process of evagination, 
 the cells increasing in number by mitosis. Toward the end of pregnancy each 
 excretory duct and its smaller ducts and acini form a distinct lobe with a rela- 
 tively small amount of connective tissue. The epithelium is low or cuboidal, 
 and fat begins to accumulate, in the seventh or eighth month, as droplets in the 
 basal parts of the cells. The droplets increase in number and in size, approach- 
 ing the inner end of the cell, until finally the cell is practically filled. At the 
 beginning of lactation the fat escapes into the lumen of the acinus, leaving a bit 
 of ragged cytoplasm with a nucleus. This regenerates into a cell capable of 
 
 Stroma 
 (dermis) 
 
 Stroma 
 
 FIG. 395. Vertical section of the anlage of the mammary gland of a human foetus of 25 cm. Nagel. 
 
 further activity; and it is probable that the same cell may become filled with 
 fat and discharge its contents several times during lactation. 
 
 During pregnancy and lactation the acini also contain leucocytes which have 
 wandered through the epithelium from the surrounding tissue. These contain 
 fat droplets and are known as colostrum corpuscles. 
 
 At the end of lactation the acini atrophy and disappear, the lobules becoming 
 masses of connective tissue and fat, which contain groups of duct-like tubules 
 and which are so closely joined with one another that they are indistinguishable 
 as lobules. 
 
 ' Anomalies. 
 
 ANOMALIES or THE SKIN. The epidermis may develop to an abnormal de- 
 gree over the entire surface of the body, forming a horny layer which is broken 
 only where the skin is folded by the movement of the members of the body 
 a condition known as hyperkeratosis. Or the abnormal development may give 
 rise to irregular patches of thick epithelium ichihyosis. In either case, hairs 
 and sebaceous glands are usually absent over the affected areas. 
 
THE DEVELOPMENT OF THE INTEGUMENTARY SYSTEM. 445 
 
 Occasionally pigment develops in excess over larger or smaller areas of the 
 skin, giving rise to the so-called navi pigmentosi. In some cases, on the other 
 hand, there is total or almost total lack of pigment in the skin and hair (usually 
 accompanied by defective pigmentation of the iris, chorioid and retina) 
 a condition known as albinism. There are also instances of partial albinism. 
 The influence of heredity in albinism is doubtful, for albinos are usually the 
 children of ordinary parents. 
 
 The angiomata (lymphangiomata, haemangiomata) found in the skin are due 
 to dilated lymphatic or blood channels, the color in haemangiomata being due 
 to the haemoglobin in the blood. 
 
 Dermoid Cysts. The congenital dermoid cysts not infrequently found in or 
 under the skin are usually situated in or near the line of fusion of embryonic 
 structures, as in the region of the branchial arches, along the ventral body 
 wall and on the back. During the fusion of adjacent structures, portions of the 
 epidermis become constricted from the parent tissue and come to lie in the der- 
 mis, where they continue to grow and produce cystic masses and sometimes 
 give rise to hairs and sebaceous glands. This type of dermoid is to be dis- 
 tinguished from that found for example in the ovary, in which derivatives of 
 all three germ layers are present (see Chap. XIX). 
 
 ANOMALIES OF THE EPIDERMAL DERIVATIVES. Occasionally hair develops 
 in profusion over areas of the skin that naturally possess only a fine, silky growth, 
 such, for example, as a woman's face. Or nearly the entire body may be 
 covered by an unusual amount of hair. Such conditions known as hyper- 
 trichosis possibly represent the persistence and continued growth of the 
 lanugo (p. 440) and in this sense are to be regarded as the result of arrested 
 development (Unna, Brandt). Congenital absence of the hair (hypotrichosis, 
 alopecia) is a rare anomaly and is usually accompanied by defective develop- 
 ment of the teeth and nails. 
 
 Sebaceous cysts, generally regarded as due to accumulation of secretion 
 in the sebaceous glands, sometimes probably represent remnants of displaced 
 pieces of epidermis apart from the hairs (Chiari) . 
 
 Supernumerary mammary glands (hypermastia) and nipples (hyperthelia) are 
 not infrequently present in both males and females. They are usually situated 
 below the normal mammae (rarely in the axillary region) , in a line drawn from 
 the axilla to the groin, and probably represent persistent and abnormally de- 
 veloped portions of the milk ridge (see p. 442) In very rare cases a super- 
 numerary gland develops in some other region (even on the thigh) . If the 
 mammary glands are morphologically allied to the sweat glands (p. 443), these 
 misplaced mammae are suggestive of anomalous development of some of the 
 sweat gland anlagen. 
 
446 TEXT-BOOK OF EMBRYOLOGY. 
 
 References for Further Study. 
 
 BROUHA: Recherches sur les di verses phases du developpement et de 1'activite de la 
 mammelle. Arch, de BioL, T. XXI, 1905. 
 
 BONNET, R.: Die Mammarorgane im Lichte der Ontogenie und Phylogenie. Ergebnisse 
 d. Anat. u. Entwick., Bd. II, 1892; Bd. VII, 1898. 
 
 KALLIUS, E.: Ein Fall von Milchleiste bei einem menschlichen Embryo. Anat. Hefte, 
 Bd. VIII, 1897. 
 
 KEIBEL, F., and MALL, F. P.: Manual of Human Embryology, Vol. I, 1910. 
 
 KRAUSE, W.: Die Entwickelung der Haut und ihrer Nebenorgane. In Hertwig's 
 Handbuch d. vergleich. u. experiment. Entwick elungslehre der Wirbeltiere, Bd. II, Teil I, 1902. 
 
 OKAMURA, T.: Ueber die Entwickelung des Nagels beim Menschen. Arch. /. Der- 
 matol. u. Syphilol., Bd. XXV, 1900. 
 
 PIERSOL, G. A. : Teratology. In Wood's Reference Handbook of the Medical Sciences, 
 Vol. VII, 1904. 
 
 SCHMIDT, H.: Ueber normale Hyperthelie menschlicher Embryonen und tiber die 
 erste Anlage der menschlichen MilchdrUsen iiberhaupt. Morphol. Arbeiten, Bd. XVII, 1897. 
 
 SCHULTZE, O.: Ueber die erste Anlage des MilchdrUsen Apparates. Anat. Anz., Bd. 
 VIII, 1892. 
 
 STOHR, P.: Entwiokelungsgeschichte des menschlichen Wollhaares. Anat. Hefte, 
 Bd. XXIII, 1903. 
 
 STRAHL, H.: Die erste Entwickelung der Mammarorgane beim Menschen. Verhandl. 
 d. Anat. Gesellsch., Bd. XII, 1898. 
 
 ZANDER, R.: Bie friihesten Stadien der Nagelentwickelung und ihre Beziehungen zu 
 den Digitalnerven. Arch. f. Anat. u. Physiol., Anat. Abth., 1884. 
 
CHAPTER XVII. 
 THE NERVOUS SYSTEM. 
 
 BY OLIVER S. STRONG. 
 GENERAL CONSIDERATIONS. 
 
 There are certain features of the nervous system in general and particularly 
 of the vertebrate nervous system, the comprehension of which makes the 
 processes of development of the nervous system in man more intelligible. 
 First, the nervous systems of the lower Vertebrates are in many respects 
 simpler than those of higher forms and their variations throw light upon the 
 causes which determine neural structures. Second, as the nervous systems of 
 all Vertebrates develop from the same germ plasm, there are resemblances 
 between certain features of both the embryonic and adult systems of lower 
 vertebrates and certain developmental stages in the higher. Certain struc- 
 tures met with in lower adult forms may be regarded as representing stages 
 of arrested development although specialized and aberrant in many respects 
 of structures found in higher forms. Vestigial structures in the developing 
 nervous systems of higher forms may be regarded as recurring developmental 
 necessities in the attainment of the adult form. 
 
 Stated in the most general terms, coordination of bodily activities in response 
 to both external and internal conditions is the biological significance of the 
 nervous system. This implies a transmission of some form of change from one 
 part to another or, in other words, conduction. This functional necessity is 
 shown structurally in the elongated form of the histological elements of the 
 nervous system. That such changes habitually pass along each element or 
 neurone in some one direction seems to find a natural structural expression in 
 the receptive body and dendrites of the neurone, and in its long transmitting 
 axone. 
 
 It is also evident that coordination can only be performed by a transmission 
 of a change from some given structure either back to that structure or to some 
 other structure to cause a responsive change. We thus have not only in the 
 vertebrate, but at a very early stage in the invertebrate nervous system, a dif- 
 ferentiation into afferent and efferent components, the two together usually 
 being termed the peripheral nervous system. The histological elements of these 
 components are the afferent and efferent peripheral neurones. All structures 
 which are so affected as to transmit the change to the afferent peripheral neu- 
 
 447 
 
448 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 rones may be conveniently termed receptors, those structures affected by the 
 efferent peripheral neurones may be termed effectors (Sherrington). Receptors 
 include various "sensory" structures whose principal function appears to be 
 to limit to some particular kind of stimulus the changes affecting the afferent 
 nervous elements connected with them. Effectors include various structures 
 (muscles, glandular epithelia) whose activities are influenced by the nervous 
 system (Fig. 396). A primitive nervous mechanism, thus composed of (i) 
 afferent peripheral neurones which transmit the stimulus from a receptor to 
 (2) efferent peripheral neurones which in turn transmit the stimulus to an 
 effector, is a simple, two-neurone reflex arc (Fig. 396). 
 
 At the same time these neurones, as they increase in number, are obviously 
 brought into relation with each other with more economy of space by having 
 
 Receptor 
 
 Effector 
 
 FIG. 396. A two-neurone reflex arc in a Vertebrate, gg.. Ganglion, van Gehuchten* 
 
 common meeting places. This, together with the factor noted below, leads to 
 the concentration of an originally diffuse nervous system, spread out principally 
 in connection with the outer (ectodermal) surface, into a more centralized 
 (ganglionic) type of nervous system, which at the same time has in part re- 
 treated from the surface layer (ectoderm) from which it was originally derived 
 
 (Fig. 397)- 
 
 Furthermore, when we consider the great number of receptors and effectors 
 in even simple forms, it is apparent that for effective coordination there must be 
 a considerable degree of complexity of association between the afferent and 
 efferent neurones. These associations may be to some extent accomplished by 
 various branches of the afferent and efferent neurones coming directly into 
 various relations with each other, but it is also evident that when a certain 
 
THE NERVOUS SYSTEM. 
 
 449 
 
 degree of complexity is reached, such an arrangement would necessitate an 
 extraordinary number of afferent and efferent neurones or an extraordinary 
 development of branches of each where they connect. Accordingly we find a 
 second category of neurones, the intermediate or central neurones which mediate 
 
 Lumbricus 
 
 Nereis. 
 
 Vertebrata 
 
 FIG. 397. Illustrating the withdrawal from the surface of the bodies 
 of the afferent peripheral neurones. After Retzius. 
 
 between the afferent and efferent peripheral neurones. These central neurones, 
 together with portions of peripheral neurones in immediate relation with them, 
 form, in all fairly well differentiated nervous systems, including those of all 
 Vertebrates, the central as distinguished from the peripheral nervous system. 
 
 FIG. 398. A three-neurone reflex arc. van Gehuchten. 
 I, Afferent peripheral neurone; 2, intermediate or central neurone; 3, efferent peripheral neurones. 
 
 The change or stimulus would now pass from receptor through (i) afferent 
 peripheral neurones, (2) intermediate neurones, (3) efferent peripheral neu- 
 rones to effector. This arrangement constitutes a three-neurone reflex arc 
 
450 TEXT-BOOK OF EMBRYOLOGY. 
 
 (Fig. 398), and is evidently capable of complicated combinations which may 
 be further increased in complexity by the intercalation in the arc of other 
 intermediate neurones. Finally, in the central nervous system certain struc- 
 tures consisting of intermediate neurones are developed which represent the 
 mechanisms for certain coordinations of the highest order. Such are the 
 higher coordinating centers (suprasegmental structures of Adolf Meyer) . 
 
 As a result of the preceding, it follows that in seeking the explanation for 
 various nervous structures there must always be kept in mind, first, their correla- 
 tion with peripheral structures and, second, the degree of development of the 
 central coordinating mechanism represented by the intermediate or central 
 neurones. The most important features common to the nervous systems of 
 all Vertebrates owe their uniformity either to a corresponding uniformity in 
 the peripheral receptors and effectors, or to a uniformity in the coordinations of 
 the stimuli received and given out by the central nervous system. Variations 
 in structure are due to variations of either the peripheral or central factor above 
 mentioned. In the lower Vertebrates the former factor plays a relatively more 
 important part than in the higher Vertebrates, the central apparatus being 
 simpler; while in the development of the higher vertebrate nervous systems the 
 dominating factor is the increasing complexity of the central mechanism. The 
 superiority of the nervous system of man does not consist, in the main, of supe- 
 riority in sense organs or motor apparatus, but in the enormous development of 
 the intermediate neurone system. 
 
 GENERAL PLAN OF THE VERTEBRATE NERVOUS SYSTEM. 
 
 The Vertebrate is an elongated bilaterally symmetrical animal progressing 
 in a definite direction, primitively perhaps by alternating lateral contractions 
 performed by a segmented lateral musculature. Associated with these char- 
 acteristics are the bilateral character of the nervous system and its transverse 
 segmentation, shown by its series of nerves, a pair to each muscle segment. 
 The definite direction of progression involves a differentiation of the forward 
 extremity of the animal, such as the location there of the mouth and respiratory 
 apparatus and the development there of specialized sense organs, the nose, eye, 
 ear, lateral line organs, and taste buds, which increase the range of stimuli 
 received by the animal and thereby render possible a greater range of responsive 
 activities in obtaining food and in reproduction. As a natural outgrowth 
 of these specializations, the highest development of the central coordinating 
 mechanism also takes place at the forward end or head. This concentration 
 and development of various mechanisms in the anterior end is usually termed 
 cephalization, and is a tendency exhibited also by various groups of Inverte- 
 brates in which the same general conditions are present. 
 
 The typical vertebrate nervous system, then, consists of a bilateral central 
 
THE NERVOUS SYSTEM. 451 
 
 nervous system connected by means of a series of segmental nerves with per- 
 ipheral structures (receptors and effectors) and exhibiting at its anterior ex- 
 tremity a higher development .and specialization in both its peripheral and 
 central parts. 
 
 The general features of the typical vertebrate nervous system are best 
 revealed by a brief examination of certain stages in its development. 
 
 The entire nervous system, except the olfactory epithelium and parts of 
 certain ganglia (see p. 452), is derived ontogenetically from an elonga f ed plate 
 of thickened ectoderm, the neural plate. This plate extends longitudinally in 
 the axis of the developing embryo, its position being usually first indicated 
 externally by a median groove, the neural groove (Fig. 410), the edges of the 
 plate being elevated into the neural folds (Fig. 411). The neural folds are 
 continuous around the cephalic end of the plate, but diverge at the caudal 
 end, enclosing between them in this region the blastopore. Even at this stage, 
 the neural plate is usually broader at its cephalic end, thereby indicating already 
 the future differentiation into brain and spinal cord (Fig. 413). The neural 
 folds now become more and more elevated (Fig. 412), presumably due in 
 part to the growth of the whole neural plate, and finally meet dorsally and fuse, 
 thus forming the neural tube (Figs. 72 and 429). The fusion of the lips of the 
 neural plate to form the neural tube usually begins somewhere in the middle 
 region of the plate and thence proceeds both forward and backward (Fig. 119). 
 The last point to close anteriorly is usually considered as marking the cephalic 
 extremity of the neural tube, and is called the anterior neuropore. 
 
 Even before the neural plate closes to form the tube, there is often a differen- 
 tiation of cells along each edge, forming an intermediate zone between the 
 neural plate and the non-neural ectoderm (Fig. 429). As the neural plate 
 becomes folded dorsally into the neural tube these two zones are naturally 
 brought together at the point of fusion of the dorsal lips of the neural plate. 
 The two zones thus brought together are not included in the wall of the neural 
 tube, but form a paired or unpaired ridge of cells lying along its dorsal surface. 
 This ridge of cells is called the neural crest (Fig. 429). Later, each half of the 
 neural crest separates from the other half and from the neural tube and passes 
 ventrally down along the sides of the tube, at the same time becoming trans- 
 versely divided into blocks of cells (Fig. 434). These masses of cells are the 
 rudiments of the cerebrospinal ganglia and differentiate into the afferent per- 
 ipheral neurones, and into some at least of the efferent peripheral visceral neu- 
 rones (sympathetic) as well as some other accessory structures (see pp. 489 
 to 494). The peripheral processes of these ganglion cells (afferent peripheral 
 nerve fibers) pass to the receptors, the central processes (afferent root fibers) enter 
 the dorsal part of the nerve tube (Fig. 430). In the case of the special sense 
 organs there is an interesting tendency on the part of portions of the neural 
 
452 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 tube, either evaginations (optic vesicles, olfactory bulbs), or ganglia, to fuse 
 with ectodermal thickenings (placodes) at the site of the future sense organs. 
 There appear to be often two series of ganglionic placodes in the head, a 
 dorsal (suprabranchial) series and a ventral (epibranchial) series, the latter 
 being often known as gill cleft organs. The former appear to be especially 
 connected with the development of the acustico-lateral system, the latter prob- 
 ably with the gustatory (see p. 462). (Fig. 399). The bodies of the efferent 
 
 Neural crest cells - 
 
 
 Suprabranchial placode 
 
 Mesoderm 
 
 Epibranchial placode ^Bj^^^^HQBS 
 
 ''^'j&vO 6 
 Rudiment of nerve -piC. 
 
 1- Notochord 
 
 3T Preoralgut 
 
 FIG. 399. Transverse section through the head of a 7 day Ammocoetes in the region 
 of the trigeminal ganglion, von Kupffer. 
 
 neurones (except the sympathetic) remain in the neural tube, lying in its 
 ventral half, and send their axones out as the efferent peripheral nerve fibers to 
 the effectors. 
 
 The formation of the neural plate and its closure into a tube are the em- 
 bryological expression of the above noted tendency of highly specialized neural 
 structures to concentrate and withdraw from the surface (p. 448). The same 
 is true of the less highly specialized placodes, in which this process is not carried 
 so far. The neural plate may thus be regarded as the oldest placode. The 
 afferent peripheral neurones would naturally originate from the borders of this 
 plate, such portions being the last to separate from the non-neural ectoderm 
 or outer surface. They may be regarded as the youngest portions, phylo- 
 genetically, of the plate, and there seems to be some variation among Chordates 
 as to the degree of inclusion of the afferent peripheral neurones in the plate. 
 
 In the neural tube thus formed, there can be distinguished four longitudinal 
 
THE NERVOUS SYSTEM. 
 
 453 
 
 plates or zones : A ventral median plate (floor plate] , a dorsal median plate (roof 
 plate], where the fusion occurred, and two lateral plates (e.g., Fig. 442). 
 
 Two points are to be noted: First, that the neural plate is a bilateral struc- 
 ture and the future development of the tube will naturally take place principally 
 in the side walls or lateral plates of the formed tube; second, that the primary 
 connection between the two side walls is the ventral median plate, the dorsal 
 median plate having been produced by a secondary fusion. This being the 
 case, the ventral connection between the two lateral plates will naturally be 
 more extensive and possibly more primitive than the dorsal. The ventral and 
 dorsal median plates do not usually develop nervous tissue, but bands of vertical 
 elongated ependyma cells. In places the roof plate expands into thin mem- 
 branes which are covered with vascular mesodermal tissue forming chorioid 
 plexuses, such as the chorioid plexuses of the lateral, third and fourth ventricles 
 (Fig. 408). 
 
 FIG. 400. Scheme of a median sagittal section through a vertebrate brain before 
 
 the closure of the neuropore. von Kupffer, 
 
 A., Archencephalon; >., deuterencephalon; Ms., medulla spinalis (spinal cord); cd., notochord; 
 en., neuronteric canal; ek., ectoderm; en., entodernv /., infundibulum; up., neuropore; pv. t 
 ventral cephalic fold; tp., tuberculum posterius. 
 
 It has already been seen that even at its first appearance the neural plate 
 exhibits a differentiation into an anterior expanded part, the brain, and a 
 posterior narrower part, the spinal cord. After closure, in many Vertebrates at 
 least, a three-fold division can be made out: (i) A caudal part of the neural 
 tube, the spinal cord, which gradually expands cranially into (2) the caudal part 
 of the brain (deuterencephalon, v. Kupffer) (Fig. 400). These two parts lie 
 above the notochord and all the typical cerebrospinal nerves are connected 
 with them. (3) Cranially, at the anterior end of the notochord, the brain wall 
 expands ventrally forming the third portion (archencephalon) . At the forward 
 extremity is seen the anterior neuropore. The deuterencephalon is thus an 
 epichordal part of the brain, while the archencephalon is prechordal. At the 
 boundary between the two is a ventral infolding of the brain wall the ventral 
 cephalic fold (plica encephali ventralis) . At this stage the brain resembles that 
 of Amphioxus in many respects. From each side w r all of the archencephalon 
 
454 TEXT-BOOK OF EMBRYOLOGY. 
 
 an evagination appears, the optic vesicle (Fig. 414) which develops into the 
 retina and optic nerve. 
 
 In the next stage (Fig. 401), there is a tendency for the neural tube to bend 
 ventrally around the anterior end of the notochord. This bending is the 
 cephalic flexure. At the same time the dorsal wall above the cephalic fold be- 
 comes expanded and is marked off from that part of the dorsal wall lying 
 caudally by a transverse constriction, the rhombo-mesencephalic fold, and from 
 the part of the dorsal wall lying cranially by another transverse fold at the 
 site of the future posterior commissure. The middle part of the brain, the 
 roof of which is thus marked off, is the mid-brain or mesencephalon. Its 
 floor is the middle projecting part of the ventral cephalic fold. The cephalic 
 expansion of the brain, practically the former archencephalon, is now the 
 
 FIG. 401. Scheme of a median sagittal section through a vertebrate brain after the formation 
 
 of the three primary brain expansions, von Kupfter, 
 
 P.. prosencephalon; M., mesencephalon; R., rhombencephalon; Ms., spinal cord; civ., chiasma emi- 
 nence; /., infundibulum; It., lamina terminalis; pv., ventral cephalic fold; pn., processus 
 neuroporicus; pr., rhombo-mesencephalic fold; r. 1 , unpaired olfactory placode; ro., recessus 
 (prae-?) opticus; tp., tuberculum posterius. 
 
 fore-brain or prosencephalon and the caudal expansion is the rhombic brain or 
 rhombencephalon. 
 
 These three primary brain expansions ("vesicles"), the fore-brain, mid- 
 brain and rhombic brain, are constant throughout the Vertebrates. Beginning 
 at the location of the former neuropore (processus neuroporicus) and passing 
 caudally along the floor of the fore-brain we have the lamina terminalis or end- 
 wall of the brain, containing a thickening which indicates the site of the future 
 anterior (cerebral) commissure, next the recessus prceopticus, then another thick- 
 ening, the chiasma eminence, and finally a diverticulum, the recessus postopticus 
 and injundibulum (Fig. 401). 
 
 At a later stage (Fig. 402), there appear two evaginations in the roof of the 
 fore-brain, the anterior epiphysis or paraphysis and the posterior epiphysis or 
 epiphysis proper (pineal body). Immediately caudal to the paraphysis is a 
 transverse infolding of the brain roof, the velum transversum. The line aa 
 
THE NERVOUS SYSTEM. 455 
 
 (Fig. 402) extending from this fold to the optic recess indicates the location of a 
 fold in the side walls in some forms and is taken by some as the boundary be- 
 tween two subdivisions of the fore-brain, the end-brain or telenccphalon and the 
 inter-brain or diencephalon. Cranial to the epiphysis proper, is a commissure 
 in the dorsal wall (commissura habemdaris^ connecting two structures which 
 develop in the crests of the side walls, the ganglia habenula. 
 
 From the dorsal part of the telencephalon is developed the pallium. The 
 ventral anterior part evaginates toward the olfactory pit, its end receiving the 
 olfactory fibers. This region is often termed the rhinencefhalon. Thickenings 
 of the basal lateral walls of the telencephalon form \h^cozpora striata. 
 
 FIG. 402. Scheme of a median sagittal section through a vertebrate brain showing 
 
 the five-fold division of the brain, von Kupfler. 
 
 T., Telencephalon; D. : diencephalon; M., mesencephalon; Mt., metencephalon; Ml., myelence- 
 phalon; c. y cerebellum; cc., cerebellar commissure; ch., habenular commissure; cp., posterior 
 commissure; cw., chiasma eminence; e., epiphysis; e 1 ., paraphysis; J., infundibulum; //., 
 lamina terminalis; />., processusneuroporicus; pr., rhombo-mesencephalicfold; pv., ventral 
 cephalic fold; ro. } recessus (prae-) opticus; si., sulcus intraencephalicus posterior; tp., tuber- 
 culum posterius. The lines aa., dd and ft indicate the boundaries between four divisions. 
 
 The roof of the mesencephalon finally develops the "optic lobes" The 
 thickened part of the roof lying immediately caudal to the rhombo-mesen- 
 cephalic fold develops into the cerebellum. The part of the tube of which this 
 forms the roof is often called the hind-brain or metencephalon, while the rest of the 
 rhombencephalon is then termed the after-brain or myelencephalon. The roof of 
 this portion, which has become very thin in the course of its development, forms 
 the epithelial part of the tela chorioidea of the fourth ventricle. The con- 
 stricted portion of the tube between the rhombic brain and mid-brain is the 
 isthmus. 
 
 The above subdivisions of the three primary expansions into five parts 
 (end-, inter-, mid-, hind- and after-brains), especially the subdivisions of the 
 rhombic brain, do not have the morphological value of the three primary 
 
456 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 divisions but have a certain value for descriptive purposes. The cavities of 
 the brain are the ventricles and their connecting passages, namely, the third 
 ventricle of the diencephalon and the fourth ventricle of the rhombencephalon, 
 the two being connected by the mid-brain cavity (aquceductus Sylvii) . The 
 telencephalon usually develops a more or less paired character, its cavities 
 being then paired diverticula of the unpaired fore-brain cavity and known as 
 the lateral ventricles. 
 
 Before the closure of the brain part of the neural tube, transverse constric- 
 tions appear across the neural plate. The transverse rings into which the 
 
 FIG. 403. Chick embryos; i, of 22 hours' incubation; 2, of 24 hours; 3, of 25^ hours; 4, of 26 
 
 hours, showing respectively 2, 5, 6, and 7 primitive segments. Hill. 
 
 cp., Caudal limit of fore-brain; />-., caudal limit of mid -brain; ., first primitive segment; 
 ps. } primitive streak; i-n, neuromeres. 
 
 tube, when completed, is thus divided are known as neuromeres. They are 
 held to represent a primitive segmentation of the head, similar, perhaps, to 
 that exhibited by the spinal nerves and segmental somatic musculature (primi- 
 tive segments) of the trunk. The neuromeres may appear before the head 
 somites. To what extent they correspond to the somites or to the visceral 
 segmentation (p. 460) and also to the cranial nerves is a matter of dispute. 
 Concerning their number there have been various views, the evidence inclining 
 to three in the fore-brain, two in the mid-brain and six in the rhombic brain 
 (Fig. 403). Their presence and number are most in doubt in the cephalic end 
 of the tube, the highly modified prosencephalon. 
 
THE NERVOUS SYSTEM. 457 
 
 The general features of the vertebrate nervous system which especially 
 illuminate conditions met with in the human nervous system are the following: 
 (i) The correlation between the peripheral structures (receptors and effectors) 
 and the nervous system. (2) The distinction between the epichordal and pre- 
 chordal portions of the brain. The latter (fore-brain) is, in accordance with its 
 anterior position (comp. p. 450), the most highly modified part of the neural 
 tube. (3) The distinction between the segmented and suprasegmental parts 
 of the brain (Adolf Meyer).* The segmental part of the brain is that portion 
 in more immediate connection with peripheral segmental structures. Its epi- 
 chordal part is spinal-like and most clearly segmental. Its prechordal part, 
 both as to its peripheral and central portions, is so highly modified that its 
 segmental character is more obscure. It and the rest of the prechordal brain 
 are most conveniently treated together as fore-brain. The suprasegmental 
 parts of the brain, or higher coordinating centers, are the cerebellum, mid- 
 brain roof and the pallium (cerebral hemispheres). Their general functional 
 significance has been mentioned (p. 450). Some of their general structural 
 characteristics are : First, that they are each expansions of the dorso-lateral 
 walls of the neural tube; second, that in them the neurone bodies are placed 
 externally and in layers (cortex), the nerve fibers (white matter) lying within; 
 third, that each appears to have originally had an especially close relation with 
 some one of the three great sense organs of the head, the olfactory, \isual or 
 acustico-lateral system; fourth, that each is connected with the rest of the brain 
 by bundles of centripetal and centrifugal fibers, and often there are specialized 
 groups of neurone bodies in other parts of the brain for the origin or recep- 
 tion of such bundles. Each higher center has also its own system of association 
 neurones. 
 
 It will accordingly be most convenient to consider: (i) the spinal cord, (2) 
 the segmental part of the epichordal brain, (3) the cerebellum, (4) the mid- 
 brain roof, (5) the prosencephalon. 
 
 Spinal Cord and Nerves. 
 
 As already brought out, there are two principal morphological differences 
 between the afferent and efferent peripheral neurones. First, the neurone 
 bodies of the former are located outside the neural tube, w^hile the neurone 
 bodies of the latter lie within the walls of the neural tube. Second, the afferent 
 
 * This distinction apparently ignores the fact that the primitive neuromeric segmentation of the 
 neural tube involves its dorsal as well as its ventral walls and thus "suprasegmental" as well as "seg- 
 mental " structures were originally segmental. This may be granted, but while the demonstration 
 of the primitive segmentation of the neural tube may be valuable as showing the primitive mechan- 
 ism which has undergone later modifications, the importance of such later modifications renders the 
 above distinction necessary. The main significance of the nervous system is its associative character 
 and its progressive development is not as a segmental, but as a more and more highly developed 
 associating mechanism. 
 
458 TEXT-BOOK OF EMBRYOLOGY. 
 
 nerves enter the dorsal part of the lateral walls of the tube, while the efferent 
 nerves leave the ventral part of the lateral walls, their neurone bodies lying in 
 this ventral part. The effect of this upon the structural arrangements within 
 the tube is the production in the tube of two columns of neurone bodies, a dorsal 
 gray column for the reception of the dorsal or afferent roots and a ventral 
 gray column containing the efferent neurone bodies. 
 
 Another important differentiation arises apparently from the important 
 physiological difference in general character between the activities of what may 
 
 FIG. 404. Transverse section through the body of a typical Vertebrate, showing the peripheral 
 
 (segmental) nervous apparatus. Froriep. 
 Small dots, afferent visceral neurones; coarse dots, afferent somatic neurones; dashes, efferent 
 
 visceral (ventral root and sympathetic) neurones; lines, efferent somatic neurones. 
 Darm, gut; Ggl. spin., spinal ganglion; Ggl. vert., vertebral sympathetic ganglion; Ggl. mesent., 
 
 mesenteric sympathetic ganglion. The peripheral sympathetic ganglionic plexuses (Auer- 
 
 bach and Meissner) are not shown. Muse., muscle; Rad. dors., dorsal root; Rad. vent., 
 
 ventral root; R. comm., white ramus communicans. 
 Two sympathetic neurones are represented as intercalated in the visceral efferent pathway. It is 
 
 doubtful if there should be more than one. 
 
 be termed the internal (visceral or splanchnic} and the external (somatic) struc- 
 tures. Internal activities are to a certain extent independent of activities 
 which have to do more with the reactions of the organism to the external world, 
 and consequently their nervous mechanisms have a more or less independent 
 character, forming what is often called the autonomic (sympathetic) system. 
 This independence is exhibited structurally by the intercalation in the per- 
 ipheral pathway of additional neurones, whose bodies form visceral ganglia 
 
THE NERVOUS SYSTEM. 459 
 
 connected in various ways among themselves and probably having their own 
 reflex arcs or plexuses. These ganglia are nevertheless to some extent under 
 the control of the efferent neurones of the central nervous system, some of 
 which send their axones to such ganglia (Fig. 404). There are thus in the 
 central nervous system two categories of efferent peripheral neurones, those 
 innervating visceral structures "via sympathetic ganglia and those innervating 
 somatic structures. The bodies of the somatic efferent neurones are located 
 in the ventral gray matter of the nerve tube, while the bodies of the splanchnic 
 efferent neurones are believed to occupy more central and lateral positions in 
 the lower half of the gray matter of the neural tube (Fig. 404). It is uncer- 
 tain whether there are similar afferent splanchnic neurones in the sympathetic 
 ganglia, and thus distinct from those in the spinal ganglia, or whether these all 
 lie in the spinal ganglia and are consequently not fully differentiated from the 
 somatic afferent neurones. 
 
 The muscular segmentation of the trunk has already been mentioned and 
 also the corresponding segmental arrangement of the spinal nerves. Local 
 extensions of this musculature and of its overlying cutaneous surface in the 
 form of fins and limbs cause corresponding increase in the size of those seg- 
 ments of the cord innervating them. This is due to the increased number of 
 afferent fibers and consequent increase in the dorsal white columns and in the 
 receptive dorsal gray columns, also to the increase in the number of efferent 
 peripheral neurones whose bodies occupy the ventral gray column (e.g., cervi- 
 cal and lumbar enlargements). (Compare also the differentiation in the 
 cervical cord and- lower medulla of the columns and nuclei of Goll for the 
 lower extremities and those of Burdach for the upper extremities). 
 
 In general, the intermediate neurones of the cord fall into two categories; 
 intersegment al (ground bundles), connecting cord segments, and those send- 
 ing long ascending bundles to suprasegmental structures (see pp. 472 and 473.) 
 
 The Epichordal Segmental Brain and Nerves. 
 
 The principal peripheral structures which exert a determining influence on 
 the structure of the epichordal brain are : The mouthy the respiratory apparatus 
 (gills and later lungs), and two specialized sensory somatic structures, the 
 acustico-lateral system and the optic apparatus. 
 
 In the gills we have essentially a series of vertical clefts forming communica- 
 tions between the pharynx and the exterior, the intervals between the clefts 
 being the gill arches. The musculature of the gill arches is morphologically 
 splanchnic (pp. 302 and 311). The gill or branchial musculature is in closer 
 relations with stimuli from the external world than is the visceral musculature 
 of the body. As a result of this the former is not of the smooth involuntary 
 
460 TEXT-BOOK OF EMBRYOLOGY. 
 
 type, like the visceral musculature of the body, but is of the striated voluntary 
 type, like the somatic musculature. The branchial receptors are naturally 
 visceral in character and there is also in this region a series of specialized 
 visceral receptors, the end buds of the gustatory system. The development of 
 this whole specialized visceral apparatus in this region of the head has appar- 
 ently caused a corresponding reduction of the somatic musculature. 
 
 The musculature of the mouth is also splanchnic, the mouth itself being- 
 regarded by many morphologists as a modified pair of gill clefts which has re- 
 placed an older mouth lying further forward in the region of the hypophysis. 
 The existence of this series of gill clefts has naturally caused a branchiomeric 
 or splanchnic segmentation of the musculature of this region as opposed to the 
 somatic muscular segmentation seen in the trunk. Whether these two kinds 
 of segmentation correspond in this region is uncertain. (In this connection see 
 Fig. 428 and p. 496.) 
 
 In the acustico-lateral system three parts may be distinguished : (i) a remark- 
 able series of cutaneous sense organs, extending in lines over the head and body 
 and known as the lateral line organs; (2) the vestibule, including the semicircu- 
 lar canals; (3) the cochlea (organ of hearing proper Cord's organ) . In the 
 higher Vertebrates, the lateral line organs have disappeared, owing to a change 
 from a water to a land habitat; the labyrinth has remained unchanged, and 
 the cochlea has undergone a much higher development and specialization. 
 
 Regarding the optic apparatus, it is sufficient to point out here that its motor 
 part, the eye muscles, is usually taken to represent the sole remaining somatic 
 musculature belonging to the head proper. 
 
 The peripheral nerves of the epichordal part of the brain have fundamen- 
 tally the same arrangements as the spinal nerves, namely, the peripheral af- 
 ferent neurone bodies are separate from the nerve tube, forming ganglia, while 
 the bodies of the efferent neurones are located centrally in the morphologically 
 ventral portions of the lateral walls of the nerve tube. There are, however, 
 important differences, clearly correlated with the peripheral differentiations and 
 specializations outlined above, and affecting the afferent and efferent nerves. 
 
 First to be considered is the afferent part of the trigeminus (Figs. 405 and 
 406). The peripheral branches of the ganglion (semilunar or Gasserian 
 ganglion) of this nerve innervate that part of the external (somatic) surfaces of 
 the head (skin and stomodaeal epithelium) which have not been encroached 
 upon by the spinal afferent nerves. This nerve is accordingly more strictly 
 comparable with the afferent spinal nerves. The central processes of the 
 semilunar ganglion cells, after entering the brain, form a separate descending 
 bundle, the spinal V. It is interesting to note that the terminal nucleus of 
 this bundle of fibers is the morphological continuation in the brain of the 
 dorsal gray column of the cord. The extensiveness of the area innervated by 
 
THE NERVOUS SYSTEM. 
 
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462 TEXT-BOOK OF EMBRYOLOGY. 
 
 the trigeminus may be partly due to disappearance or specialization of anterior 
 somatic nerves and also to the growth of the head. 
 
 The organs of the lateral line are innervated by a quite distinct system of 
 ganglionated afferent nerves whose central connections are nearly identical with 
 those of the acoustic (Fig. 405). With the disappearance of the lateral line 
 organs and the specialization of the cochlear part of the ear vesicle, there is a 
 disappearance of the lateral line nerves (comp. Figs. 405 and 406) and a well- 
 marked division of the acoustic nerve into vestibular and cochlear portions, 
 the former innervating the older vestibulo-semicircular canal portion, the latter, 
 the more recent cochlea. Centrally, the vestibular nerve forms also a descend- 
 ing bundle of fibers and has its own more or less specialized terminal nuclei. 
 The latter is also true of the cochlear nerve. 
 
 The afferent portions of the facial, glossopharyngeal and vagus nerves in- 
 nervate the splanchnic receptors of the pharyngeal and branchial surfaces as 
 well as of a large part of the viscera. The facial, glossopharyngeal and vagus 
 also innervate the specialized splanchnic receptors, the gustatory system men- 
 tioned above. This system of taste buds has a very extensive development in 
 certain lower Vertebrates, especially the Bony Fishes. In the latter the 
 system of nerves innervating these structures is naturally much more extensive 
 and its central terminations and nuclei cause important modifications of the 
 medulla. In Mammals the remnants of this system are represented by the 
 taste buds in the mouth, the nerves innervating them being the chorda tympani 
 branch of the facial and the lingual branch of the glossopharyngeal (Fig. 406). 
 The central branches of the ganglia of these three nerves, after entering the 
 brain, form a descending bundle of fibers, ihejractus solitarius (or communis). 
 
 The somatic musculature of the head, as above mentioned, is usually taken 
 to be represented by the eye muscles and, later, the tongue muscles. The 
 tongue is one of the newer structures, rising in importance with the change to 
 a land habitat, and its muscles are probably an invasion from the neck region 
 caudal to the branchial arches (p. 321). The eye muscles are innervated by 
 the III, IV and VI cranial nerves, the tongue muscles by the XII which is a 
 more recent addition to the cranial nerves. All of these nerves are charac- 
 terized by having their neurone bodies located in the most medial (morpholog- 
 ically most ventral) portions of the lateral brain walls, and they all, except the 
 IV, emerge near the mid-ventral line. In these respects they resemble the 
 major or somatic part of the ventral spinal roots. (For illustration see Figs. 
 427, 405 and 406). 
 
 The splanchnic musculature of the jaws and the branchial arches is inner- 
 vated by the efferent portions of the V, VII, IX, X (and XI). The neurone 
 bodies or nuclei of origin of these nerves lie more laterally than those of the III, 
 IV, VI and XII, and their axones also leave the nerve tube more laterally 
 
THE NERVOUS SYSTEM. 
 
 463 
 
464 TEXT-BOOK OF EMBRYOLOGY. 
 
 along with the incoming afferent fibres. These nerves all exhibit a character- 
 istic segmental arrangement corresponding to that of the gill clefts. The 
 VII, IX, and the various nerves making up the X, divide dorsal to the cor- 
 responding gill clefts into prebranchial and postbranchial branches, also 
 giving off suprabranchial branches. The efferent element, or component, 
 forms a part of each postbranchial branch. These relations are shown clearly 
 in the accompanying diagrams (Figs. 405 and 406). Part of the vagus also 
 innervates the viscera and this nerve is thus divisible into branchial and visceral 
 portions. 
 
 Two peculiarities may be noted in regard to these splanchnic nerves : First, 
 that the afferent portions have ganglia resembling those of the spinal nerves; 
 second, that the branchial efferent portions consist simply of one neurone 
 proceeding all the way from the nerve tube to the muscle innervated, thus 
 resembling the somatic rather than the visceral nerves of the trunk. As al- 
 ready noted (p. 459), these nerves regulate activities somatic in character but 
 involving splanchnic structures. It is thus seen that the dominating factor is 
 functional rather than morphological present functional necessities modify 
 those of the past. 
 
 With the change from a water to a land habitat and the accompanying 
 disappearance of gills and appearance of lungs, we have various suppressions 
 and modifications of the branchial musculature (Fig. 406). There are two 
 striking specializations of the branchial musculature. One is the origin of 
 the facial (mimetic) musculature in the highest Vertebrates. This is derived 
 from the muscles of the hyoid arch, innervated naturally by extensions of the 
 facial nerve. The other is a specialization of muscles, probably of the caudal 
 branchial arches, into cervico-cranial muscles (head-movement), innervated by 
 what may be considered a caudal extension of the vagus nerve, namely, the 
 spinal accessory (p. 496). The splanchnic laryngeal musculature and its 
 nerves show a certain degree of specialization (sound-production) in higher 
 forms. The efferent V is naturally a large constant nerve, in correlation with 
 the uniformly developed jaw musculature in all jaw-bearing (gnathostome) 
 Vertebrates (Figs. 405 and 406). These various changes in peripheral 
 structures are thus due either to environmental influences or to developments 
 within the central nervous system (p. 450). One of the most important en- 
 vironmental influences is the change from a water to a land habitat. The 
 influence of the central nervous system is shown in the further development 
 and specialization of a number of peripheral structures as motor "instru- 
 ments" of suprasegmental mechanisms. 
 
 The effects, then, of the peripheral arrangements upon the arrangements 
 within the neural tube are: (i) The formation of separate tracts and terminal 
 nuclei for (a) the unspecialized somatic afferent V nerve (spinal V and posterior 
 
THE NERVOUS SYSTEM. 
 
 465 
 
 horn) ; (b) the specialized somatic vestibular nerve (descending or spinal VIII 
 and various terminal nuclei) and also the cochlear nerve and its various termi- 
 nal nuclei; (c) the splanchnic afferent nerves (tractus solitarius and its 
 terminal nuclei). (2) The separation of the efferent neurone bodies lying in the 
 neural tube into two main longitudinal series of nuclei (a) the somatic efferent 
 nuclei, occupying a more medial position, their axones emerging from the neural 
 tube as medial ventral nerve roots; (b) the splanchnic efferent nuclei occupying 
 a more lateral position, their axones emerging laterally and forming mixed 
 roots with the incoming afferent fibers (Fig. 407). 
 
 FIG. 407. Diagram of a transverse section through the lower human medulla showing the origin of 
 the X and XII cranial nerves. Schdfer. 
 
 g y Ganglion cell of afferent vagus sending central arm (root fiber) to solitary tract (f.s.} and col- 
 lateral to the nucleus of the solitary tract (/. s. n.). It is not certain that the axones of the 
 cells of this terminal nucleus take the course indicated in the figure, n.amb., nucleus am- 
 biguus and d. n. X, dorsal efferent nucleus of the vagus, both of which send out axones as the 
 efferent root fibers of the vagus. These two represent the lateral or splanchnic efferent nuclei 
 of this region, n. XII, nucleus of the hypoglossus the axones of which pass out medially as 
 efferent root fibers of the XII. This nucleus represents the medial or somatic efferent nuclei 
 of this region, f.s.. tractus solitarius or descending roots of vagus, glossopharyngeus and 
 facial; d. V., descending spinal root of the trigeminus; r., restiform body; o., inferior olivary 
 nucleus (''olive"); pyr~ pyramid. 
 
 The intermediate neurones of the epichordal segmental brain, as well as 
 of the cord, fall into two general systems. One of these is the system of 
 inter segmental neurones, connecting various segments of the segmental brain 
 and cord. This system may be collectively termed the ground bundles (of the 
 cord) and reticular formation (of the brain) . These neurones may be regarded 
 as not only furnishing the various reflex communications between the afferent 
 and efferent cerebrospinal peripheral neurones, but as also forming a system 
 upon which the descending neurones from the higher coordinating centers 
 (suprasegmental structures) act, before the efferent peripheral neurones are 
 reached. This system may thus be regarded in general as more closely associ- 
 
466 TEXT-BOOK OF EMBRYOLOGY. 
 
 ated with the efferent than with the afferent peripheral neurones. Certain 
 tracts in this system and their nuclei of origin have reached a considerable 
 degree of differentiation, due principally to association with higher centers. 
 Among these differentiated reticulo-spinal tracts may be mentioned the medial 
 longitudinal fasciculus, the rubro-spinal tract, and the various tracts from 
 Deiters' nucleus. The other system consists of nuclei which are associated 
 with the afferent axones as their terminal nuclei, the axones of which form long 
 afferent tracts to suprasegmental structures. Especially well-marked differ- 
 entiations of nuclei and tracts of this system are usually due both to its con- 
 nections with peripheral structures and with the higher centers. The principal 
 afferent suprasegmental tracts to the cerebellum are mentioned below (p. 466). 
 Those to mid-brain roof and (via added neurones) to pallium are the medial 
 fillet or lemniscus from the nuclei of the columns of Goll and Burdach, the 
 lateral lemniscus from the cochlear terminal nuclei and other ascending tracts 
 from terminal nuclei of peripheral afferent neurones. 
 
 The Cerebellum. 
 
 The other great factor (see p. 450) affecting the structure of the epichordal 
 brain is the development in it of two higher coordinating centers or supraseg- 
 mental structures, the cerebellum and optic lobes. The cerebellum is a develop- 
 ment of the dorsal part of the lateral walls of the tube just caudal to the isthmus 
 and was probably primarily developed in correlation with the acustico-lateral 
 system, especially with the lateral line and vestibule-semicircular canal 
 portions (p. 460). Due probably to the fact that it is thus an important 
 "equilibrating" mechanism, the cerebellum has acquired other important con- 
 nections besides its original ones with the acustico-lateral system. In the 
 vertebrate series it is especially developed in all active balancing forms (Fig. 408) . 
 In Mammals it has acquired important connections with the greatly enlarged 
 pallium (cerebral hemispheres), in accordance with its general regulative in- 
 fluence (static and tonic) upon motor reactions. The great development of the 
 cerebellum has profoundly modified the anatomical arrangements of the rest of 
 the brain and cord, owing to its numerous and massive connections. The fol- 
 lowing important masses of gray matter and fiber bundles may be mentioned as 
 cerebellar^a^em^_connections : Clarke's column cells, and other cells in the 
 cord, and the spino-cerebellar tracts; the lateral nuclei, inferior olives and the 
 restiform body in the medulla; part of the pes pedunculi, the pontile nuclei and 
 middle peduncle of the cerebellum. The superior cerebellar peduncle to the 
 red nucleus, together with tracts to Deiter's nucleus, belong to the cerebellar 
 efferent connections. The cortico-pontile portion of the pes, the pontile nuclei 
 and the middle peduncle represent the most recently developed cerebral con- 
 nections (comp. pp. 470-472 and Fig. 409). 
 
THE NERVOUS SYSTEM. 467 
 
 The Mid-brain Roof. 
 
 This expansion of the dorsal part of the neural tube constitutes a higher 
 coordinating center for impulses received by various somatic nerves spinal, 
 cochlear and optic. Owing to its being, in all forms below Mammals, the 
 principal visual center, the optic part (optic lobes) varies in proportion to the 
 development of the eye, animals with poorly developed eyes having small optic 
 lobes. In Mammals, the ^>ptic part (anterior corpora quadrigemina or col- 
 liculi) is relatively less important, owing to a taking over of a portion of its 
 coordinating functions by the neopallium (pp. 470, 472), but the cochlear part 
 (posterior corpora quadrigemina or colliculi) has increased in importance, 
 owing to the rise of the cochlear organ (organ of Corti). The centripetal and 
 centrifugal connections of the mid-brain roof are not so massive or extensive 
 and consequently do not modify the other parts of the brain and cord as pro- 
 foundly as do those of the cerebellum. It sends descending tracts to after- 
 brain and cord segments. 
 
 The Prosencephalon. 
 
 The division of this part of the brain into the telencephalon and diencephalon 
 has already been indicated (p. 455). In the diencephalon may be noted (i) the 
 absence of the notochord ventral to the brain, thereby permitting a ventral ex- 
 pansion of the brain walls, the Jvy^p^wlamuSy associated with an organ not 
 well understood, the hypophysis; (2) certain more or less vestigial structures, 
 such as the pineal eyes (epiphyses), and other primitive structures, such as 
 the ganglia habenulae, in the dorsal part, this dorsal portion being collectively 
 termed the epithalamus; (3) nuclei in (i) and (2) connected with olfactory 
 and gustatory tracts; (4) receptive nuclei for the optic tract and the cochlear 
 path from the posterior colliculus; (5) receptive nuclei for secondary tracts from 
 the end stations of more caudal somatic ganglia (nuclei of Goll and Burdach 
 and medial lemniscus). The last two (4 and 5) constitute the ihalamus and 
 increase in importance in the higher Vertebrates (see p. 470, Fig. 409). 
 
 In the telencephalon there may be roughly distinguished an anterior and basal 
 part, the rhinencephalon, in especially intimate relations with the olfactory nerve; 
 a thickening of the basal wall, the corpus striatum^smd a thinner- willed dorsal 
 part, the pallium. The latter may be regarded in a sense as a dorsal develop- 
 ment of the corpus striatum and first appears as a distinct structure in the 
 Amphibia. 
 
 The peripheral or segmental apparatus which are connected with the pros- 
 encephalon are the highly modified optic and olfactory organs. While the optic 
 apparatus primarily originates from the prechordal brain, in the lower Verte- 
 brates its highest coordinating center, as mentioned above, lies partly in the 
 
468 TEXT-BOOK OF EMBRYOLOGY. 
 
 epichordal portion (optic lobes). It is possible that this connection is secon- 
 dary and contingent upon two functional necessities, the importance of cor- 
 relation with stimuli coming via more caudal nerves (cochlear and spinal 
 nerves), and the innervation of its motor apparatus by epichordal nerves, the 
 III, IV and VI. With the development of the neopallium in Mammals (see p. 
 477) and the consequent projection of visual stimuli upon it, the lower pre- 
 chordal (thalamic) centers form part of the newer pathway to the neopallium 
 and thus increase in importance, while the optic lobes recede, assuming the 
 position of a reflex center, especially for the visual motor apparatus. 
 
 The olfactory nerves enter the anterior extremity of the brain and are con- 
 nected by secondary and tertiary tracts with regions lying more caudally, where 
 in some cases the olfactory stimuli are associated with gustatory and probably 
 with visual stimuli. One of these regions is the hypothalamus which receives 
 both olfactory and gustatory tracts (Herrick) . More dorsal olfactory pathways 
 pass to the epithalamus. Both epithalamus and hypothalamus give rise to de- 
 scending systems which doubtless ultimately reach efferent nuclei. In fact, this 
 part of the brain presents, apparently, a complicated primitive mechanism for 
 the correlation especially of olfactory and gustatory stimuli, also to some extent 
 of visual Stimuli and stimuli via the trigeminal nerve, the whole forming a sort 
 of oral sense, probably controlling the feeding activities (Edinger). 
 
 The next factor in the further development of this part of the brain is the 
 rise in importance of the pallium upon which at first are projected mainly 
 olfactory stimuli (Fig. 408). 
 
 A further and still more extensive development of the pallium arises when 
 other kinds of stimuli are projected to a considerable extent upon it, thus giving 
 rise to a distinction between the older olfactory pallium (archipallium) and the 
 newer non-olfactory pallium (neopallium) . The latter appears first in the lateral 
 dorsal portion of the pallial wall and by its subsequent development the archi- 
 pallial wall is rolled inward upon the mesial surface of the hemispheres. 
 Further changes consist in the extension caudally of this portion pari passu with 
 the extension caudally of the neopallium and then the practical obliteration 
 of its middle portion by the great neopallial commissure, the corpus callosum 
 (Fig. 408, G and H). 
 
 In addition to the increasing projection of stimuli from all parts of the body 
 upon the neopallium and the consequent increase in centripetal fiber termina- 
 tions and in centrifugal neurone bodies lying in its walls, a second factor in 
 the development of the neopallium is the enormous increase of its association 
 neurones. It is the latter feature which especially distinguishes the human 
 from other mammalian brains. 
 
 The biological significance of these changes lies in the fact that there is thus 
 produced a mechanism not only for the association of all kinds of stimuli, but 
 
THE NERVOUS SYSTEM. 
 
 469 
 
 FIG. 408. A-F (Edinger) are sagittal sections showing structures lying in the median line and also 
 paired structures (e.g., pallium) lying to one side of the median line. The cerebellum is 
 black. It is doubtful whether the membranous roof in A indicated as pallium is strictly 
 homologous with that structure in other forms. In B, Pallium indicates prepallial structures. 
 
 Aq. Syl., Aquseductus Sylvii; Basis mesen. y basis mesencephali; Bulb, olf., bulbus olfactorius; Corp. 
 striat., corpus striatum; Epiph., epiphysis; G. h., ganglion habenulae; Hyp., hypophysis; 
 Infund., infundibulum; Lam. t., lamina terminalis; Lob. elect., lobus electricus; L. vagi, 
 lobus vagi; L. opt., mid-brain roof; Med. obi., medulla oblongata; Opt., optic nerve; Pl.chor., 
 plexus chorioideus; Rec. inf., recessus infundibuli; Rec. mam., recessus mammillaris; Saccus 
 vase., saccus vasculosus; Sp. c., spinal cord; ventr., ventricle; v. m. a., velum medullare 
 anterius; v.m. p., velum medullare posterius. 
 
 G and H show the mesial surface of the cerebral hemispheres in a low (G) and high (H) Mammal. 
 G. Elliot Smith, Edinger, slightly modified. 
 
 The exposed gray matter of the olfactory regions is shaded, the darker shade indicating the archi- 
 pallium (preterminal area and hippocampal formation), the lighter shade indicating the 
 rhinencephalon, which consists of the anterior and the posterior (principally pyriform) olfactory 
 
470 TEXT-BOOK OF EMBRYOLOGY. 
 
 also for very complex coordinations between these stimuli. In this way an 
 extensive symbolization and formulation of individual experience (memory, 
 language, etc.) can take place. The formulated experience of one generation 
 can be immediately transmitted (by education in the broad sense of the term) 
 to the plastic late-developing neopallia of the next generation. In this 
 way a racial experience may be rapidly built up without the direct inter- 
 vention of the slow processes of heredity and natural selection and each gen- 
 eration profit by the accumulated experience of past generations to a much 
 greater extent. The nervous mechanism, the pallium, is provided by in- 
 heritance; experience is not inherited but " learned." The pallial associative 
 mechanisms are continuously modified by their activities, thus affecting the 
 character of subsequent pallial reactions (associative memory). Such reac- 
 tions are usually termed psychical or conscious, as distinguished from the 
 reflex reactions of other parts of the nervous system. 
 
 In the course of these developments the pallium or cerebral hemispheres 
 have enormously increased in size until in man they overlap all the other parts 
 of the brain. Naturally the extensive connections of the neopallium with the 
 rest of the brain have profoundly modified the latter. Among the new struc- 
 tures which have on this account been added to the older structures of the rest of 
 the brain, the following may be mentioned: (i) The centripetal connections of 
 the neopallium, consisting mainly of what are usually termed the thalamic radi- 
 ations. These consist essentially of a system of neurones passing from the 
 above mentioned termini in the thalamus of general somatic, acoustic and optic 
 ascending systems to certain areas in the cerebral hemispheres. In this system 
 we can distinguish (a) the continuation of the fillet (general somatic) to the cen- 
 tral region (somaesthetic area) of each hemisphere; (b) the optic radiation from 
 the lower thalamic optic center (lateral geniculate body) to the calcarine 
 (visual) area of the hemisphere; (c) the acoustic radiation from the medial 
 geniculate body of the thalamus to the upper temporal region (auditory area) 
 of the hemisphere. Associated with these last two connections are the increase 
 
 lobes. In Amphibia and Reptiles the hippocampal formation includes all or nearly all of the 
 mesial surface. As the early neopallium appears in the lateral hemisphere walls, the neo- 
 pallial commissural fibers first pass across the median line in the ventral or anterior com- 
 missure. With the increase of the neopallium and its extension on the mesial hemisphere 
 walls, its commissural fibers pass across more dorsally via the archipallial or fornix com- 
 missure (psalterium) forming the neopallial commissure or corpus callosum, the great de- 
 velopment of which nearly obliterates the anterior hippocampal formation. 
 
 Com. ant., Anterior commissure; corp. callosum, corpus callosum; Fimbr., fimbria; Fiss. hippo- 
 campi, hippocampal fissure; Lam. t., lamina terminalis; Lob. olf. ant., anterior olfactory lobe; 
 Lob. pyriformis, pyriform lobe; Psalt., psalterium (fornix commissure); Sept. pell., septum 
 pellucidum; Tub. olf., tuberculum olfactorium. Only a part of the gray (cortex) of the hip- 
 pocampal formation appears, as the gyrus dentatus, on the mesial surface; the remainder forms 
 an eminence, the cornu Ammonis, on the ventricular surface. This invagination is indicated 
 externally by the hippocampal fissure. The exposed fiber bundle forming the edge of this 
 formation (fimbria) passes forward (fornix and its commissure) and thence descends, as the 
 anterior pillar of the fornix, behind the anterior commissure. The anterior pillar is partly 
 indicated by a few lines in this region in the figure. 
 
THE NERVOUS SYSTEM. 
 
 471 
 
 FIG. 409. Principal afferent and efferent suprasegmental pathways (excepting the archipallial con- 
 nections, the efferent connections of the mid-brain roof and the olivo-cerebellar connections). 
 Neopallial connections are indicated by broken lines. Intersegmental connections are omitted. 
 Some peripheral elements are indicated. Each neurone group (nucleus and fasciculus) is in- 
 dicated by one or several individual neurones. Decussations of tracts are indicated by an X. 
 
 OC., Acoustic radiation, from medial geniculate body to temporal lobe; br. con]., brachium con- 
 
472 TEXT-BOOK OF EMBRYOLOGY. 
 
 of the geniculate bodies and the diminution of the mid-brain in importance 
 already alluded to (p. 467). (2) The centrifugal connections consisting of (a) 
 the pyramids passing from the precentral area of each hemisphere to various 
 lower efferent neurones, or neurones affecting the latter, and forming part of the 
 internal capsule and pes pedunculi ; (b) fibers from various parts of the hemis- 
 phere, forming the greater part of the rest of the internal capsule and pes, and 
 terminating principally in the pontile nuclei whence a continuation of this 
 system (the fibers of the middle peduncle), passes to the cerebellar hemisphere. 
 The great increase in size of the cerebellar hemispheres, of the contained 
 nuclei dentati, and probably of the superior cerebellar peduncles are further 
 effects of this new connection, which has already been alluded to (see Cere- 
 bellum, p. 466), (Fig. 409.) 
 
 Another important effect of the development of the pallium is the assump- 
 tion by man of the upright position, due both to the specialization of the 
 hand to execute pallial coordinations and its consequent release from locomo- 
 tion, and also to the overhanging of the eyes by the enlarged cranium. The 
 great increase of cerebellar connections may be partly due to the new 
 problems of equilibrium connected with the upright position. 
 
 GENERAL DEVELOPMENT OF THE HUMAN NERVOUS SYSTEM DURING 
 
 THE FIRST MONTH. 
 
 One of the earliest stages in the development of the human nervous system 
 is shown in the 2 mm. embryo of about two weeks (Fig. 410). This shows 
 the stage of the open neural groove. The appearance of a transverse section 
 of the neural plate, groove and folds, in other forms, is shown in Figs. 411 
 and 412. 
 
 The neural folds now become more and more elevated and finally meet, thus 
 forming the neural tube as previously described (p. 451). The fusion of the 
 neural folds begins in the middle region and thence extends cranially and cau- 
 
 junctivum (superior cerebellar peduncle); brack, pon., brachium pontis (middle cerebellar 
 peduncle); b. q. i., brachium quadrigeminum inferias (a link in the cochlear pathway) ; c. g. I., 
 lateral or external geniculate body; c.g.m., medial or internal geniculate body; c.qitad., cor- 
 pora quadrigemina; f.cort.-sp., cortico-spinal fasciculus (pyramidal tract);/, c. p.-f. frontal 
 cortico-pontile fasciculus (from frontal lobe); f.c.-p.t., temporal cortico-pontile fasciculus 
 (from temporal lobe); /. c.-p.o., occipital cortico-pontile fasciculus (from occipital lobe); 
 f.cun., fasciculus cuneatus (column of Burdach); f.grac., fasciculus gracilis (column of 
 Goll) ; /. s.-t., tract from cord to mid-brain roof and thalamus (sometimes included in Gowers* 
 tract); f.sp.-c.d., dorsal spino-cerebellar fasciculus (tract of Flechsig); f.sp.-c.v., ventral 
 spino-cerebellar fasciculus (tract of Gowers, location of cells in cord uncertain); lem. lat., 
 lateral lemniscus or lateral fillet; lemniscus 1 med., medial lemniscus or fillet (the part to the 
 thalamus is mainly a neopallial acquisition); n.coch., cochlear nerve; n. cun., (terminal) 
 nucleus of the column of Burdach; n.grac., nucleus of the column of Goll; n.dent., nucleus 
 dentatus; n. opt., optic nerve; n.r., nucleus ruber (red nucleus); pes ped., pes peduncu'.i 
 (crusta); pulv. thai., pulvinar thalami; Pyr., pyramid; rod. ant. y ventral spinal root; rod. post,. 
 dorsal spinal root; rod. opt., optic radiation (from lateral geniculate body, and pulvinar ( ?), 
 to calcarine region) ; somaes., bundles from thalamus to postcentral region of neopallium; 
 s p. gang., spinal ganglion; thai., thalamus. 
 
THE NERVOUS SYSTEM. 473 
 
 dally. The stage of partial closure of the neural tube is shown in Eternod's 
 figure of a human embryo of 2.1 mm. (Fig. 413, b). This order of closure in- 
 dicates, to some extent, the order of subsequent histological development; the 
 extreme caudal and cephalic extremities are more backward than the parts 
 which close first. The last point to close anteriorly marks, as stated previously 
 (p. 451), the cephalic extremity of the neural tube and is the anterior neuropore. 
 As indicated in Eternod's embryo, the anterior end of the neural plate is broader 
 even before its closure; thus when the tube is completed its anterior end is more 
 expanded. This expansion is the future brain, the narrower caudal portion 
 
 Yolk sac 
 
 Amnion 
 
 Neural groove 
 
 Neurenteric 
 canal 
 
 Belly stalk 
 
 Chorion 
 
 FIG. 410. Dorsal view of human embryo, two millimeters in length, with yolk sac. 
 
 von Spee, Kollmann. 
 The amnion is opened dorsally. 
 
 being the future spinal cord. Before the closure of the brain part of the tube 
 the beginnings of the three primary brain vesicles are also indicated (Fig. 120). 
 At this stage the neural plate shows no differentiation into nervous and sup- 
 porting elements. The neural tube is composed of the two lateral walls and 
 the median roof and floor plates (comp. p. 453) (Figs. 345 and 442). 
 
 The appearance of the anterior end of the neural tube with the closure com- 
 pleted, except the anterior and posterior neuropores, is shown in the model of 
 one half of the tube. The external appearance and also the inner surfaces are 
 shown in Figs. 414 and 415. At this stage the cephalic flexure (see p. 454) is 
 already quite pronounced, the cephalic end of the brain tube being bent ven- 
 
474 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 trally at about a right angle to the longitudinal axis of the remaining portion of 
 the tube. This bending begins before the closure of the cephalic part of the 
 neural tube (Fig. 120). From each side of the brain near the cephalic ex- 
 tremity is an evagination of the brain wall, the beginning of the optic 'vesicles. 
 
 Ectoderm 
 
 Mesoderm 
 
 x Chorda anlage Entoderm 
 
 FIG. 411. Transverse section through dorsal part of embryo of frog (Rana fusca). 
 x, Groove indicating evagination to form mesoderm. 
 
 Ziegler. 
 
 The process of evagination and consequently the location of the vesicle begins 
 before the closure of the tube. 
 
 Dorsal and anterior to the optic vesicles can be seen a slight unpaired pro- 
 trusion of the dorsal wall, the beginning of the pallium. The area basal to it and 
 
 Prim. Intermed. 
 seg. cell mass 
 
 Parietal and 
 visceral mesoderm 
 
 Chordal 
 plate 
 
 Coelom Entoderm Blood vessels 
 FIG. 412. Transverse section of dog embryo with ten pairs of primitive segments. Bonnet. 
 
 extending a short distance into the anterior wall of the optic vesicle is the site of 
 the future corpus striatum (Figs. 414 and 415). 
 
 Caudal to the pallium and separated from it by a slight constriction (in- 
 dicated best by the ridge on the inner wall) is another protrusion of the dorsal 
 wall, the roof of the diencephalon. Still further caudally and separated from the 
 
THE NERVOUS SYSTEM. 
 
 475 
 
 roof of the diencephalon by another slight constriction is another expansion of 
 the dorsal wall, the roof of the mid-brain or of the mesencephalon which arches 
 over the cephalic flexure. It is separated by another constriction (plica 
 rhombo-mesencephalica) from the rhombic brain or rhombencephalon, which latter 
 tapers into the cord. A ventral bulging of the rhombencephalon indicates the 
 future pons region (Figs. 414 and 415). 
 
 Heart 
 
 Ant. entrance to 
 prim, gut (Ant. 
 "Darmpforte") 
 
 Post, entrance to 
 prim, gut (Post. 
 "Darmpforte") 
 
 Cerebral plate 
 
 Amnion 
 
 Yolk 
 (cut edge) 
 
 Yolk sac 
 
 Belly stalk 
 
 Neural tube 
 
 Primitive 
 segment 
 
 Neural fold 
 Neural groove 
 
 Neural fold 
 
 FIG. 413. (a) Ventral view; (6) dorsal view of human embryo with 8 pairs of primitive 
 
 segments (2.11 mm.). Eternod. From models by Ziegler. 
 
 In b the amnion has been removed, merely the cut edge showing; in a the yolk sac has 
 
 been removed. 
 
 Even at this early stage the cavity of the caudal part of the rhombencephalon 
 is expanded dorsally due to an expansion of the roof plate, which forms only the 
 narrow dorsal median part of the rest of the tube. This expansion reaches its 
 maximum about opposite the auditory vesicle. 
 
 The principal changes in form during the next two weeks are the following 
 (Figs. 416 and 472): The cephalic flexure becomes still more pronounced so 
 that the anterior end of the neural tube is folded back upon the ventral side of 
 the rest of the brain, an effect probably enhanced by the expansion of the 
 
476 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 FIG. 414. Lateral view of the outside of a model of the brain of a human 
 embryo two weeks old. His. 
 
 Diencephalon 
 
 Pallium 
 
 Mesencephalon 
 
 Rhombq- 
 mesencephalic fold 
 
 Rhombencephalon 
 
 Neuropore 
 Corpus striatum 
 P. f. 
 Optic evagination 
 
 Ventral cephalic fold 
 (Seesel's pocket) 
 
 Pons region 
 
 FIG. 415. Lateral view of inner side of the same model shown in Fig. 414. 
 P.f. is the ridge corresponding to the peduncular furrow on the outer side. 
 
THE NERVOUS SYSTEM. 477 
 
 ventral wall of the anterior portion (Figs. 416 and 472). In the space thus 
 enclosed the dorsum sellae is subsequently formed. Associated with this 
 increase of the cephalic flexure is an increased prominence of the mid-brain 
 roof. The pontine flexure has begun, there being now a bending of the whole 
 tube in the pons region, the concavity of the bend being dorsal. At the same 
 time there is a corresponding tendency for the roof of the rhombencephalon to 
 become shorter and wider. There is also a further thinning of the above 
 mentioned expanded portion of the roof plate in this region, and associated 
 with this a thrusting of the thick lateral walls outward at the top so that they 
 come to lie almost flat instead of vertically as in the cord. From the cord 
 to the place of greatest width above mentioned, this dorsal thrusting apart 
 
 FIG. 416. Profile view of a model of the brain of a human embryo during the third week. His. \ 
 A, Optic vesicle; A.v., auditory vesicle; Br, pons region; H, pallium; Hh. cerebellum; J, isthmus; 
 M, mid-brain; N and /?/, medulla; XK, cervical flexure; Pm, mammillary region; 2>, in- 
 fundibulum; Z, inter-brain or diencephalon. 
 
 of the lateral rhombic walls obviously becomes more and more pronounced. 
 In front of this region of greatest width, the roof plate becomes narrower and 
 the dorsal parts of the walls (alar plates) form the rudiment of the cerebellum, 
 the rest of the rhombic brain forming the medulla oblongata. Each lateral 
 wall of the rhombic brain is now divided into a dorsal longitudinal zone or 
 plate (alar plate) and a ventral zone or plate (basal plate) by a longitudinal 
 furrow along its inner surface, the sulcus limitans. A study of the external 
 appearances and transverse sections of this part of the brain tube will make 
 these relations clear (Figs. 456, 436 to 439 and 427). Neuromeres are also 
 present at this stage (see p. 489). In the meantime the neural tube has also 
 become bent ventrally at the junction of the brain and cord, forming the cervical 
 
478 TEXT-BOOK OF EMBRYOLOGY. 
 
 flexure. The pallium has increased in size and now forms a considerable 
 prominence on the brain tube. Its boundaries are also much more clearly 
 marked off (see Fig. 471). On the inner side of the tube, the area below 
 the bulging of the pallium is the corpus striatum. Externally, just below the 
 bulging, we have the region where the olfactory lobes are differentiated. The 
 proximal part of the optic evagination has become longer and narrower. The 
 ventral expansion of the diencephalon is the hypothalamus, the portion of the 
 diencephalon dorsal to the latter being the thalamus. Two slight protrusions 
 of the ventral wall of the hypothalamus have appeared; the caudal one is the 
 mammillary region, the anterior one the infundibulum. The cavity of the 
 diencephalon (third ventricle) is connected by the mid-brain cavity (iter or 
 aquaductus Svlvii) with the rhombic brain cavity or iourth ventricle. 
 
 HISTOGENESIS OF THE NERVOUS SYSTEM. 
 
 The neural plate is at first a simple columnar epithelium. The various 
 processes by which this is converted into the fully formed nervous system are : 
 (i) cell proliferation; (2) cell migration; (3) cell differentiation. These proc- 
 esses are not entirely successive in point of time, but overlap each other. Cell 
 division is present from the first, increases to a certain period in development 
 and then practically ceases; cell migration is partly a necessary concomitant and 
 resultant of cell division, and cell differentiation is in part due to the growth of 
 the cytoplasm and is in part a result of environmental differences produced by 
 these processes. In development the following stages may be distinguished : 
 
 (i) Stage of indifferent epithelium; (2) appearance of nerve elements 
 (neurones) and resulting differentiation into supporting and nerve elements; 
 (3) growth of neurones and resulting differentiation and development of (a) 
 peripheral neurones, (b) lower intermediate or intersegmental neurones, (c) 
 neurones of higher centers and neurone groups in connection with them (supra- 
 segmental neurones). These stages do not occur simultaneously throughout the 
 whole neural tube, some parts being more backward in development than others 
 (p. 473). In general the spinal cord and epichordal segmental brain are most 
 advanced in development. Furthermore, the ventral part of the brain tube 
 precedes the dorsal. The most backward part of the whole neural tube is the 
 pallium. 
 
 The various phases of /0rw-differentiation of the neurone are (i) the 
 development of the axone and, later, of its branches; (2) the growth of the 
 dendrites; (3) the formation of accessory coverings or sheaths, the neurilemma 
 and the myelin (medullary) sheath. The principal internal differentiations 
 are (i) the appearance of the neurofibrils; (2) the chromophilic bodies of 
 Nissl; (3) pigment. These latter may all be regarded as products of the 
 nucleus and undifferentiated cytoplasm of the nerve-cell. 
 
THE NERVOUS SYSTEM. 479 
 
 Epithelial Stage. Development of Neuroglia. 
 
 From the very first, the neural plate exhibits dividing cells similar to those 
 seen in the non-neural ectoderm. The cell divisions are indirect and the 
 mitoses are confined to the outer part of the ectoderm, occurring between the 
 outer ends of the resting epithelial cells (Fig. 417). These dividing cells have 
 been termed by His germinal cells. When the neural tube is formed, the 
 mitoses are still confined to the outer, now the luminal, surface, this being a 
 general phenomenon in developing epithelial tubular structures. As a result 
 the daughter nuclei migrate away from the lumen. 
 
 In the most advanced parts of the neural tube (see p. 478), the mitoses in- 
 crease in number up to about the fourth to sixth week of development, and then 
 diminish and finally nearly disappear about at the end of two months. At 
 about the time the blood vessels penetrate the tube, the mitoses .are no longer 
 entirely confined to the proximity of the lumen. 
 
 As a result of proliferation, the epithelial wall very early assumes the ap- 
 pearance of a stratified epithelium at least there are several strata of nuclei. 
 There are at this stage in many forms two layers, an outer or marginal layer, 
 free of nuclei, and an inner or nuclear layer (Figs. 418 and 419). In a human 
 embryo, however, of about two weeks this division into layers is yet hardly 
 evident, though there are several strata of nuclei. Apparently these layers are 
 not well-marked until the radial arrangement of the myelospongium, as 
 described below, has become more pronounced. 
 
 Accompanying the above changes, changes also manifest themselves in the 
 character of the cells. At about the time of the closure of the neural tube, the 
 cell boundaries become indistinct and finally practically obliterated, thus form- 
 ing a syncytium, the myelospongium. At the same time, the syncytium becomes 
 very alveolar in structure and a general spongioplasmic reticulum is formed (Figs. 
 418 and 419) by the anastomosing denser strands (trabeculae) of protoplasm. 
 At a very early stage (two weeks), these trabeculae unite along the inner and 
 outer walls of the neural tube forming internal and external limiting mem- 
 branes. The nuclei of the neural tube have at first an irregular arrangement 
 in the reticulum, at least in the human embryo. This is followed by a more 
 radial arrangement of both nuclei and protoplasmic filaments (Fig. 420) , form- 
 ing nucleated radial masses of protoplasm the sponglioblasts (Figs. 419 to 
 422). There is some dispute as to the loss, complete or incomplete, of identity 
 of the epithelial cells in the formation of the spongioblasts. According to 
 Hardesty, they are formed by a collapse of the epithelial cells and a rearrange- 
 ment of their denser parts into axial filaments. The radial arrangement does 
 not extend into the outer part of the neural tube which, retaining its irregular 
 reticular character, is now non-nucleated in the human embryo and forms the 
 
480 
 
 TEXT-BOOK OF EMBRYOLOGY, 
 
 *s:aaf 
 
 
 
 a 
 
 FIG. 420. 
 
 FIG. 417. From the neural tube of an embryo rabbit shortly before the closure of the tube, g, Germi- 
 nal or dividing cell; m, peripheral zone, position of the later marginal layer. His. 
 
 FIG. 418. Pig of 5 mm., unflexed. Just after closure of the neural tube. Segment of a vertical 
 section of the lateral wall of the tube, g, Germinal cells; m, beginning of marginal layer; 
 mil, internal limiting membrane; r, radial columns of protoplasm. The resting nuclei lie in 
 the inner or nuclear layer. Hardesty. 
 
THE NERVOUS SYSTEM. 
 
 481 
 
 marginal layer. The increase in the thickness and circumference of the walls 
 of the tube and the resulting tensions may be a factor in this arrangement 
 cf the protoplasmic filaments. At the boundary between the marginal and 
 nuclear layers the reticulum appears to be especially dense. 
 
 With the further increase and development of the nervous elements (see 
 p. 485) the radial arrangement of the spongioblasts noted above becomes more 
 and more obliterated. As shown by Golgi preparations, in their migration from 
 the lumen (Fig. 422) the spongioblasts lose their connection with the lumen, 
 
 mil 
 
 mv 
 
 FIG. 421. Hardesty. Combination drawing from sections of pig of 15 mm. The upper part is 
 from a section of the same stage as the lower but stained by the Golgi method. By migra- 
 tion and differentiation the mantle layer has been formed. The cells remaining near the 
 lumen form the ependyma layer (ep.). b, Boundary between mantle and marginal layers; 
 ep, ependyma; mli and mle, internal and external limiting membranes; mv, differently 
 arranged mid-ventral portion of the marginal layer; r, radial filaments; cs, connective tissue 
 syncytium. 
 
 their peripheral processes become abbreviated and disappear, and they finally 
 differentiate into the irregular branching neuroglia cells (Fig. 423). According 
 to Hardesty, there is simply a general nucleated mass which changes form 
 pari passu with changes in the enclosed differentiating nervous elements, 
 finally assuming shapes dependent upon the character of the spaces between 
 the formed nervous elements. An exception to this is a layer of nucleated 
 elements which remain next the lumen and form the ependyma cells which still 
 
 FIG. 419. Pig of 7 mm., unflexed. Segment from the ventro-lateral wall of the neural tube; 
 
 g, Germinal cells; mli, internal limiting membrane; mle, external limiting membrane 
 
 r, radial, axial filaments of the syncytial protoplasm; p, beginning of pia mater. Hardesty. 
 FIG. 420. Pig of 10 mm., "crown-rump" measurement. Segment from lateral wall of neural tube. 
 
 b, boundary between nuclear layer and marginal layer (m). Other references same as 
 
 in 419. Hardesty. 
 a indicates the zone in which the dividing cells are located. Later, it is composed of the inner ends 
 
 of the ependyma cells (column layer of His). 
 
482 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
THE NERVOUS SYSTEM. 
 
 483 
 
 send radial extensions into the wall of the neural tube (Figs. 421 and 422). 
 These cells develop cilia projecting into the lumen. 
 
 A still later differentiation m the supporting elements of the tube is the ap- 
 pearance of neuroglia fibers a product of the spongioblastic protoplasm, but 
 differing from it chemically (Fig. 423). The exact relation of these neuroglia 
 fibers to the nucleated neuroglia cells in the adult is a matter of dispute. 
 
 " W/^>^3yftl^fE*&^iM5w5?;d 
 
 . . . * / jfSiRSf^ 
 
 B d f 
 
 FIG. 423. Hardesty. Combination drawing from transverse sections of the spinal cord of 20 cm, 
 pig. Showing the first appearance of neuroglia fibers, a, Xeuroglia cell as shown by the 
 Benda method of staining; a', similar cell by the Golgi method; b and &', non-nucleated 
 masses; d, free nuclei; e and/, differentiating neuroglia fibers; s, '"'seal-ring" cells, envelop- 
 ing myelinating nerve-fibers. 
 
 With the penetration of blood vessels into the neural tube a certain amount of 
 mesodermal tissue is brought in. How much of the supporting tissue of the 
 nervous system is derived from the mesoderm is uncertain, but it is most 
 probable that it is relatively small in amount and is confined principally to the 
 connective tissue of the walls of the blood vessels. 
 
 Early Differentiation of the Nerve Elements. 
 
 It has been seen that some of the actively dividing cells (germinal cells) at 
 first simply increase the ordinary epithelial elements of the tube which in turn 
 form the myelospongium, the spongioblasts and finally the ependyma and the 
 neuroglia. Other daughter cells produced by the division of the germinal cells 
 
484 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 differentiate into nerve cells as described below. Still others probably migrate 
 outward as indifferent cells, which later proliferate and form cells which differ- 
 entiate into neuroglia and nerve cells. 
 
 According to recent researches (Cajal), by means of the silver stain of Cajal 
 the first indication of the differentiation of cells into nerve cells is the appear- 
 ance of neurofibrils in the cytoplasm of cells near the lumen. The part of the 
 cell in which the neurofibrils first appear is called the fibrillogenous zone 
 (Held) and is usually in the side furthest from the lumen. The cells in which 
 these appear are apparently without processes, and are accordingly termed 
 apolar cells (Cajal). (Fig. 424.) 
 
 FIG. 424. Section through the wall of the fore-brain vesicle of a chick embryo of 3 J days. Cajal. 
 
 A, b and c, Differentiating nerve cells in apolar stage, the neurofibrils are black; a, cell in a stage 
 transitional to the bipolar stage; B, bipolar cells; c (at lower right corner), cone of "growth" 
 of developing axone; e, tangential axone. The cells in the bipolar stage have migrated out 
 ward, but the neuroblast or mantle layer has not yet been differentiated. 
 
 The next step in the development of many, but probably not all, of these cells 
 is their transformation into bipolar cells by the outgrowth of two neurofibrillar 
 processes, one directed toward the lumen, the other, usually thicker, toward the 
 periphery, the cell body at the same time beginning to migrate outward (Fig. 424) . 
 This bipolar stage may be regarded as conditioned to some extent by the radial 
 arrangement of the other elements, due in turn partly to the original epithelial 
 structure and partly, possibly, to tensions produced by the growth of the tube. 
 It is also interesting as recalling conditions in sensory epithelia and in the 
 cerebrospinal ganglia. The bipolar stage is most common probably in those 
 parts where the elements show a radial arrangement in the adult. Such are the 
 layered cortices of the mid-brain and pallium. Nerve cells maintaining a con- 
 nection, by central processes, with the luminal wall have been described in lower 
 Vertebrates. This connection may be explained as due to a persistence of the 
 central processes of cells in the bipolar stage. 
 
THE NERVOUS SYSTEM. 485 
 
 The next stage is a monopolar stage produced by the atrophy of the luminal 
 process. Cells in this stage are the neuroblasts of His, the peripheral processes 
 being the developing axones (Fig. 425). As seen in ordinary stains, the above 
 differentiation of the neuroblasts is marked by a corresponding differentiation 
 of the nuclear layer into an inner layer retaining its previous characteristic radial 
 arrangement, and an outer layer characterized by fewer nuclei more irregularly 
 arranged. The latter layer is the mantle, or neurone layer (Fig. 442) . There 
 are now three layers: (i) inner (nuclear), (2) mantle (neurone) and (3) marginal. 
 The mantle layer is thus produced by the migration and differentiation of cells 
 into neuroblasts. While this process may begin near the lumen (apolar nerve 
 
 FIG. 425. Dorsal portion of the lumbar cord of a chick embryo of three days. Cajal. 
 A, B, Cells in the apolar stage with fibrillogenous zones; B shows transition to the bipolar stage; 
 E, further advanced bipolar cell; G, cells in monopolar stage or neuroblasts of His; a, giant 
 cone of growth. These cells have migrated to the outer part of the nuclear layer, thereby 
 forming the beginning of the mantle layer. 
 
 cell of Cajal) and progress as the cell has moved somewhat further away (bipolar 
 stage), the monopolar stage is probably reached only when such cells form a part 
 of the mantle layer. In other words, the mantle layer is created by the migra- 
 tion to a certain location and differentiation to a certain stage of the primitive 
 nerve cells. The mantle layer, as previously stated, probably also contains 
 indifferent cells which may by further proliferation and subsequent differentia- 
 tion become either glia or nerve cells.* The looser arrangement of the cells of the 
 mantle layer is probably in some measure due to the growth of the dendrites which 
 appear soon after the axones. It may be also due to the beginning vascularization 
 of the tissues with resulting transudates (His) which usually, however, begins 
 somewhat later. The association in time of vascularization and further growth 
 
 * It is an open question as to how late in development these " extra ventricular " cell- divisions, in- 
 volving " indifferent " cells, may occur. The neuroglia cells, however, like other supporting elements, 
 preserve this capacity of division indefinitely, as shown by the increase in neuroglia cells in patho- 
 logical conditions. 
 
486 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 of neurocytoplasm (dendrites) is significant. When the cell-proliferation near 
 the lumen has ceased, the supply of new cells ceases, and as the cells of the 
 inner layer continue to differentiate into cells of the mantle layer, the inner 
 layer, being no longer replenished from within, is reduced to the single layer of 
 cells which remain behind as ependyma cells (p. 481). 
 
 Differentiation of the Peripheral Neurones of Cord and 
 Epichordal Segmental Brain. 
 
 Efferent Peripheral Neurones. The differentiation of a mantle or 
 neurone layer from the outer part of the original nuclear layer is practically 
 universal throughout the whole neural tube. It appears first and is conse- 
 quently most advanced, however, in the ventral part of the lateral walls of the 
 cord and epichordal brain. The axones of neuroblasts occupying the basal plate 
 of this region of the neural tube grow out through the external limiting mem- 
 
 FIG. 426. Ventral part of wall of lumbar cord of 70- hour duck embryo, showing efferent root 
 
 fibers first emerging from cord (combined from two sections) . Cajal. 
 A, Spinal cord; B, perimedullary space; C, meningeal membrane; a, b, cones of radially directed 
 
 axones; c, d, cones of transversely directed axones; D, bifurcated cone; E,F, cones crossing 
 
 perimedullary space; G, aberrant cones. 
 
 brane and emerge as the efferent ventral root fibers. The appearance of these 
 early root fibers in the duck is shown in Fig. 426. The process is similar in 
 the human embryo and begins about the third week. The neurones thus 
 differentiated are the efferent peripheral neurones. 
 
 In some forms, at least, cells appear to migrate out from the tube along with 
 the efferent root fibers. Their fate is not certain, but they probably either 
 metamorphose into the neurilemma cells or possibly form part of the sympa- 
 thetic ganglia (see p. 492). In general the questions affecting the differentiation 
 
THE NERVOUS SYSTEM. 
 
 487 
 
 of the efferent fibers are the same as for the afferent and are further dealt 
 with later (pp. 492-495). 
 
 The majority of the efferent root fibers pass to the differentiating somatic 
 muscles which they innervate, forming specialized terminal arborizations (the 
 motor end plates). The fibers to the dorsal musculature form, together with 
 the afferent fibers (p. 490), the dorsal branch of the peripheral spinal nerve ; 
 others form part of the ventral branch which sends a branch mesially toward 
 the aorta. Some of the fibers of the mesial branch take a longitudinal course. 
 This mesial branch is the white ramus communicans and terminates in the 
 various sympathetic ganglia which are later formed along its course (p. 491). 
 
 FIG. 427. Diagram (lateral view) of the brain of a 10.2 mm. human embryo (during the fifth week), 
 showing the roots of the cranial nerves. His. 
 
 Ill, Oculomotor; IV, Trochlear; V, Trigeminus (m, efferent root, s, afferent root); VI, Abducens; 
 VII, Facial; VIII, Acoustic (c, cochlear part, v, vestibular part); IX, Glossopharyngeus; 
 X, Vagus; XI, Spinal accessory; XII, Hypoglossus. ot., Auditory vesicle; Rh.l., rhombic 
 lip. The two series of efferent roots (medial and lateral) are clearly shown. 
 
 (Comp. Figs. 263, 265, 432 and 404.) The fibers to the sympathetic ganglia 
 are the visceral (splanchnic) fibers of the ventral root. There are a few other 
 fibers which grow dorsally from neuroblasts in the ventro-lateral walls of the 
 cord and thence out vio_the dorsal root (Fig. 430) . They also are probably 
 visceral. 
 
 In the cord the splanchnic fibers, w r ith the exception above noted, issue with 
 the somatic fibers in a common ventral root. In the epichordal segmental brain, 
 however, there is a differentiation of the efferent neuroblasts of the basal plate 
 into two series of nuclei, a medial and a lateral. The medial series consists of 
 
488 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 the nuclei of the XII, VI, IV and III cranial nerves, and their axones grow 
 out as medial ventral root fibers (except the IV) (Fig. 427) to the differenti- 
 ating muscles of the tongue and eyeball which they respectively innervate. 
 These muscles are probably somatic and their nerves are the somatic efferent 
 cranial nerves corresponding with the greater part of the fibers of the ventral 
 roots of the cord (compare p. 462). The lateral series consists of the nuclei of 
 the efferent portions of the roots of the XI, X, IX, VII and V cranial nerves 
 and their axones grow out as lateral roots (Fig. 427) to the differentiating 
 striated branchial (splanchnic) muscles (sternocleidomastoideus, trapezius, 
 
 N.triqem. (motor) 
 
 --N.focialis 
 
 - ; - N.aeusticus 
 -------- N.abducens 
 
 ----- N.glo3jqpharyf\g. ( 
 N. vaguj 
 
 N.hypoglo3sus 
 
 FIG. 428. Diagram of the floor of the 4th ventricle of a 10 mm. human embryo, illustrating the 
 rhombic grooves and their relations to the cranial nerves. The point of attachment of the 
 acoustic and the sensory root of the trigeminal nerve is shown by dotted circles; the motor 
 nuclei are represented by heavy dots. Streeter. 
 
 pharynx, larynx, face and jaw) and also to muscles of the viscera (via sympa- 
 thetic?). The lateral nuclei and their roots are thus splanchnic. (Cf. pp. 
 302-3, 462, 464.) Their root fibers, with the incoming afferent fibers, form the 
 mixed roots of these nerves. The positions of these various nuclei and their 
 roots are clearly indicated in Figs. 427, 436-439, 447 and 451 and require no 
 further description. Additional details are mentioned in connection with 
 the afferent cranial nerves. In the region of the vagus nerve, there are 
 differentiated two series of lateral nuclei, a ventro-lateral (nucleus ambiguus X) 
 and a dorso-lateral (dorsal efferent nucleus X) (comp. Fig. 407). Fig. 452 
 
THE NERVOUS SYSTEM. 
 
 489 
 
 apparently indicates the beginning of this differentiation. The significance 
 of the dorso-lateral nucleus is uncertain. It possibly sends fibers to the 
 sympathetic system. 
 
 At about this period six transverse rhombic grooves are plainly marked in 
 the floor of the fourth ventricle, standing in relation with the nerves of this 
 region (Fig. 428). They are ordinarily regarded as neuromeric, but the above 
 relation would indicate that they have primarily a branchiomeric character 
 (Streeter). It will be noticed that each of the three main ganglionic masses 
 of this region (p. 495) corresponds to two of the grooves. (Comp. p. 465). 
 
 The further development of the efferent neurones exhibits phases common 
 to many other nerve-cells with a large amount of cytoplasm (somatochrome 
 cells). The further development of the neuro fibrils of cell body and dendrites 
 
 Neural crest 
 
 Ectoderm 
 
 Neural crest 
 
 c 
 
 -^'Primitive 
 segment 
 
 FIG. 429. Three stages in the closure of the neural tube and formation of the neural crest (spinal 
 ganglion rudiment). From transverse sections of a human embryo of 2.5 mm. (13 pairs of 
 primitive segments, 14-16 days), von Lenhossek. 
 
 is, according to some observations, at first confined to the peripheral portions, 
 leaving a clear zone in the vicinity of the nucleus. The chromophilic sub- 
 stance first appears as distinct granules about the end of the second month, 
 there being apparently a diffuse chromophilic substance present before this 
 period. The chromophilic granules also are first differentiated in the per- 
 ipheral portions of the cell. A still later differentiation is the pigment, which 
 probably does not appear till after birth. This increases greatly in amount 
 in later years and is then an indication of senility of the nerve-cell. 
 
 Afferent Peripheral and Sympathetic Neurones. It has already been 
 mentioned (p. 451) that in the closure of the neural tube certain cells forming 
 an intermediate band between the borders of the neural plate and the non- 
 neural ectoderm are brought together by the fusion of the lips of the plate 
 
490 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 and form a ridge on the dorsal surface of the neural tube, this ridge being 
 known as the neural crest (Fig. 429). 
 
 In the SPINAL CORD, at three weeks, the neural crest has separated from the 
 cord and split into two longitudinal bands. The ventral border of each band 
 shows a transverse segmentation into rounded clumps of cells, forming the 
 rudiments of the spinal ganglia which later become completely separated. The 
 efferent roots have begun to develop but the afferent roots appear later (fourth 
 week, Fig. 434). The cells composing these rudiments are polyhedral 
 or oval rather than columnar and proliferation still proceeds among them 
 A differentiation of these cells soon begins. Some, usually larger cells 
 
 FIG. 430. Part of a transverse section through the cord and spinal ganglion of a 56-hour chick 
 
 embryo (combined from two sections) . Cajal. 
 A, Efferent cell of dorsal root; B, cone of growth of central process (afferent dorsal root fiber) of 
 
 spinal ganglion cell; C, bifurcation of afferent root fibers in cord, forming beginning of dorsal 
 
 funiculus or dorsal white column of cord. 
 
 begin to assume a bipolar shape. Their central processes grow toward the 
 dorsal part of the lateral walls (alar plate) of the neural tube which they enter 
 (Fig. 430), becoming afferent (dorsal) root fibers. These fibers enter the mar- 
 ginal layer and there divide (Figs. 430 and 441) into ascending and descend- 
 ing longitudinal arms which constitute the beginning of the dorsal (posterior) 
 juniculus of the cord. The peripheral processes of the developing ganglion 
 cells grow toward the periphery, uniting with the ventral root and forming 
 with it the various branches of the peripheral spinal nerve (compare Figs. 
 263, 265, 432 and 404). Other peripheral branches pass as a part of the 
 white ramus communicans to the sympathetic ganglia through which they 
 
THE NERVOUS SYSTEM. 
 
 491 
 
 proceed to the visceral receptors. These latter fibers are thus visceral afferent 
 fibers. 
 
 It is now known that the spinal ganglion is a much more complicated struc- 
 ture and has more forms of nerve cells than was formerly realized. The dif- 
 ferentiation into these various types has not yet been fully observed. The 
 bipolar cells, however, become unipolar in the manner shown in Fig. 431. 
 The cell body first becomes eccentrically placed with reference to the two proc- 
 esses and then, as it were, retracts from them, remaining connected with them 
 by a single process. This change may economize space. 
 
 According to most authorities, many of the cells of the neural crest do not 
 cease their migration by forming spinal ganglia, but undifferentiated cells 
 
 FIG. 431. Section of spinal ganglion of 1 2-day chick embryo. Cajal. 
 
 Showing various stages of the change from the bipolar to the unipolar condition. A,B, Unipolar 
 cells; C, D, F, G, cells in transitional stage; E, bipolar cell; H, immature cell. The neuro- 
 fibrils are well shown. 
 
 wander still further ventralward and form, probably also undergoing still 
 further proliferation, the rudiments of the various sympathetic ganglia, becom- 
 ing subsequently differentiated into the sympathetic cells. By this migration 
 there is first formed a longitudinal column of cells ventral to the spinal ganglia 
 (Fig. 433) and, later, in relation with the white communicating rami (Fig. 
 432). This column becomes segmented (seventh week), forming ultimately 
 the ganglia of the vertebral sympathetic chain. In the meanwhile, the 
 cells of the column proliferate in places, forming rudiments which, by migra- 
 tion and further differentiation, form the ganglia of the various prevertebral 
 sympathetic plexuses (cardiac, cceliac, pelvic, etc.). Further migrations lead to 
 the formation of the ganglia of the peripheral plexuses (Auerbach, Meissner, 
 
492 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 etc.). All these ganglia, probably, are innervated by fibers from the white 
 ramus, along whose course they apparently migrated. The axones of their 
 cells pass to visceral structures either in the same segment or, via the longi- 
 tudinal chain, to those of other segments. Some also join the branches of 
 the peripheral spinal nerves (gray ramus). Fibers of the white ramus also pass 
 longitudinally in the chain to vertebral ganglia of other segments. The 
 possibility previously mentioned (p. 486) of a contribution to the sympa- 
 thetic ganglia by cells migrating out along with the ventral roots must be kept in 
 mind. It would seem a priori more probable that these latter would furnish 
 the efferent sympathetic cells, but the efferent cells predominate in the sym- 
 
 Spinal cord 
 Spinal ganglion 
 
 Ventral root 
 
 Mixed spinal nerve 
 Myotome 
 
 Sympathetic ganglion ; 
 
 FIG. 432. From a transverse section of a chick embryo of 4^ days. Neumayer. 
 
 pathetic and must thus be regarded as derived partly or wholly from the 
 neural crest which furnishes at least the major part of all the sympathetic 
 cells. 
 
 It seems probable that not all the cells of the neural crest form nerve cells, 
 but some, usually smaller cells, become closely applied to the spinal ganglion 
 cells, forming amphicytes, while others (lemmocytes) wander out along the nerve 
 fibers and become the neurilemma cells, forming the neurilemma. These cells 
 in this case would be quite strictly comparable to the glia cells of the neural 
 tube. According to another view, the neurilemma cells are of mesodermal 
 origin. While this point cannot be considered entirely determined, it seems 
 fairly certain that in some types at least the former view is correct, removal of 
 the neural crest having resulted in the formation of efferent nerves without 
 
THE NERVOUS SYSTEM. 493 
 
 neurilemma cells (Harrison). The modification into neurilemma cells seems 
 to be accomplished by their enveloping the axones and becoming closely 
 applied to them. 
 
 The peripheral nerve grows toward the periphery as a bundle of fibers which forms, as 
 seen in many stains, a common fibrillated mass, dividing at its extremity into the develop- 
 ing branches of the nerve. The lemmocytes closely envelop each of these growing tips, 
 but proximally only envelop the main nerve trunk (Bardeen). The final clear separation of 
 
 ~^Spinal ganglion rudiment 
 
 mm 
 
 / 
 
 I </*S I 
 
 Notochord ^ ^" ( 
 
 
 ^^--Sympathetic ganglion rudiment 
 
 FIG. 433. From a transverse section through a shark (Scyllium) embryo of 15 mm., showing the 
 
 origin of the sympathetic ganglion. Onodi. 
 
 In mammals the cells are more scattered and their origin from the spinal ganglion 
 rudiment not so clear. 
 
 the fibrillated mass into the individual nerve fibers is accomplished, according to Gurwitsch, 
 by these accompanying cells forming septa within the mass and finally enveloping each 
 axone as its neurilemma sheath. Growth in bundles appears to be characteristic also of the 
 axones (tracts and fasciculi) of many neurone groups in the central nervous system. 
 
 Owing to the presence of these migrating cells as well as of mesodermal cells, 
 the peripheral nerves in their earlier stages appear cellular in character; later the 
 fibrous elements predominate, the nuclei becoming more scattered and changing 
 into the flatter nuclei characteristic of the neurilemma (Fig. 432). According to 
 one view (Balfour), the nerve fibers themselves are differentiated from the cyto- 
 
494 TEXT-BOOK OF EMBRYOLOGY. 
 
 plasm of these cell-strings and are thus multicellular structures. Still another 
 view is that of Hensen, according to which the fibers are a differentiation in 
 situ from preexisting syncytial bridges uniting the parts connected subsequently 
 by the formed nerve fibers. This differentiation may not be primarily con- 
 nected with the neuroblasts (Apathy, Paton) . An intermediate view between 
 this and the outgrowth view of His is that of Held, according to which the 
 neurofibrillar substance is an outgrowth from the neuroblast body, or at least a 
 differentiation proceeding from that body, but always within the preexisting 
 cellular bridges of Hensen. The differentiating fiber is thus always intracel- 
 lular instead of intercellular as according to the His-Cajal view. The experi- 
 ments of Harrison above alluded to, in which the accompanying migrating cells 
 were eliminated and naked axones (axis-cylinders) nevertheless developed, ap- 
 parently disposes of the cell-string theory of Balfour. The growth of the 
 fibers in the marginal layer of the central nervous system is also unfavorable to 
 this theory. The apparently proven capacity of growing axones to find their 
 way through foreign tissues (aberrant regenerating nerve fibers, Cajal), 
 through ventricular fluid (Cajal), and even through serum (Harrison) seems to 
 throw the weight of evidence in favor of the view of His. The latter is the 
 view adopted in this description, though many of the most important facts of 
 development are not perhaps entirely irreconcilable with any of these views. 
 The general conception of the neurone is affected by these questions and the 
 related question of anastomoses between the nervous elements, whether present 
 at all, and if present, whether primary or secondarily acquired. 
 
 From the above it would seem that the cells of the neural crest have the 
 capacity of differentiating into afferent neurones, efferent (sympathetic) neurones 
 and supporting cells. Other cells of the jneural crest differentiate into the 
 chromaffine cells of the suprarenal glands and similar structures (p. 426). 
 
 There are several views as to the development of the myelin sheath. Ac- 
 cording to one view (Vignal), it is a product of the neurilemma cells, being 
 formed in a manner analogous to the formation of fat by fat cells. Accord- 
 ing to Wlassak, the various substances composing the myelin (fat, lecithin 
 and protagon) are first found in the central nervous system in the protoplasm 
 of the spongioblasts, their probable original source being the blood of the 
 meningeal blood vessels. Later, the myelin is laid down around the axones, 
 appearing first as drops or granules. The same process takes place in the 
 peripheral nervous system. The supporting elements of the nervous system 
 thus would have a chemical as well as a mechanical function. Another view 
 (Gurwitsch) is that the myelin is a product of the axone and is, at its first 
 appearance, quite distinct from the neurilemma cells. 
 
 As the appearance of the myelin sheath is a final stage in the development of the neurone, 
 the various neurone systems would naturally become myelinated in about the same sequence 
 
THE NERVOUS SYSTEM. 495 
 
 in which their axones develop. " This is probably true in a general way, but the development 
 of both axones and sheaths requires further study before any law can be exactly formulated. 
 Coarse fibers apparently become medullated early, the sheaths of such fibers being usually 
 thicker. 
 
 Although the myelin sheath is apparently an accessory structure, its formation is of 
 great importance, not only from the above reason, but also because its appearance possibly 
 indicates the assumption by the neurone of its capacity for the precise performance of its 
 final functions. The functional significance of the myelin sheath is not, however, entirely 
 clear. Its importance is enhanced by the fact that its integrity depends upon the integrity 
 of its neurone and that we possess precise stains for demonstrating both its normal and 
 abnormal conditions. 
 
 In the region of the RHOMBENCEPHALOX, the neural crest very early exhibits 
 a division into three masses: a glossopharyngeo-vago-accessorius, an acustico- 
 facialis, and a trigeminus. These masses soon become separated from each 
 other and from the neural tube, the glossopharyngeus also shoeing a partial 
 separation from the vago-accessorius mass (Fig. 434). 
 
 The vago-accessorius group, at about three weeks, is a mass of cells much 
 larger at the cranial end and continuous by a narrow band of irregular cells 
 with the spinal neural crest. The cranial end of the mass shows a partial 
 division into a dorsal and ventral part. The former becomes the ganglion of 
 the vagus root, the latter the ganglion of the trunk (nodosum). The glosso- 
 pharyngeus mass likewise shows a division into a dorsal group of cells, the 
 future ganglion of the root and a ventral group, the future ganglion of the 
 trunk (petrosum). The two ventral groups are associated with epidermal 
 thickenings (placodes), but it is doubtful whether any ganglion cells are 
 derived from the thickenings. These thickenings probably represent the 
 thickenings associated in water-inhabiting Vertebrates with the development of 
 certain sense organs, either lateral line or epibranchial (see p. 452). At this 
 stage there are no afferent fibers, the cells not yet being differentiated into 
 neurones. Some fibers found among the cells are efferent (see p. 488). The 
 glossopharyngeus cells lie in the region of the third branchial arch, the vagus 
 in the region of the fourth. 
 
 During the fourth and fifth weeks the processes of the cells begin to develop 
 (Fig. 434), and the cell masses finally become definite ganglia with afferent root 
 fibers passing into the neural tube and peripheral processes passing outward, 
 forming, with the associated efferent fibers, the peripheral branches of the nerves 
 in question (Fig. 435). The root and trunk ganglia of the vagus and glosso- 
 pharyngeus, respectively, are also now connected by fiber bundles instead of 
 cellular strands. At the same time there is a diminution of cells in the caudal 
 part of the vago-accessorius group, this part finally being composed almost ex- 
 clusively of efferent fibers emerging from the lateral surface of the medulla and 
 cord . A few groups of cells (accessory root ganglia) persist, however, and develop 
 
496 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 into ganglion cells, some being found there at birth (Streeter) . This would in- 
 dicate the presence of a small and hitherto undetected afferent element in the 
 spinal accessory nerve, which is usually regarded as purely efferent. The spinal 
 accessory nerves are thus identical with the vagus in their early development 
 and consist at first of a homologous series of efferent roots and ganglia. This 
 
 /x-x-x/ gang, crest. 
 
 Qpthal dlv. 
 
 Sup. max d 
 N.maSticatorfus. 
 Infmax.di 
 
 D.I. 
 
 FIG. 434. From a reconstruction of the peripheral nerves in a human embryo of 
 
 4 weeks (6.9 mm.). Streeter. 
 
 JII-XII, III to XII cranial nerves; C.I, D. I.., L.I., 5.7., ist cervical, ist dorsal, ist lumbar, and 
 ist sacral nerves, respectively; I, 2, 3, branchial arches; Ot. v., auditory vesicle; IX-X-XI 
 gang, crest, ganglionic or neural crest of IX, X and XI cranial nerves. Fiber masses are 
 represented by fine lines, ganglion cell masses by dots. 
 
 indicates that the spinal accessory might be regarded as a specialized part 
 of the vagus extending caudally into the cord (Streeter) (see p. 464).* 
 
 From this point on, the further development of the efferent fibers of the X 
 and XI nerves and of the peripheral processes of their ganglia is the further 
 
 * According to another view (Bremer), the spinal accessory nuclei and roots are to be regarded as 
 representing a specialization of lateral nuclei of the ventral gray column of the cord whose root fibers 
 pass in the dorsal branches of the spinal nerves to the dorsal trunk musculature (p. 487, ccmp. Fig. 
 404) . According to this view, the muscles innervated by the XI would be somatic. The possible 
 homology of the lateral efferent nuclei and roots of the medulla with those dorsal root fibers of the 
 cord which arise from cells in the ventral gray column (p. 487 and Fig. 430) may be mentioned in 
 this connection. 
 
THE NERVOUS SYSTEM. 
 
 497 
 
 growth of the various branches of these nerves and their connection with the 
 differentiating structures innervated by them. At the same time there is an in- 
 creasing concentration of the cells, thereby forming more definite ganglionic 
 
 Vesicula auditiva 
 
 Gang, acusticum 
 Gang, semilunare n.V 
 
 Gang. radicisn.IX 
 Gang, petrosum 
 
 Gang, radicis n.X 
 
 N. frontalis""" 
 
 N. mandibularis 
 Gang, geniculatum --"' 
 N. chorda tympani .---' 
 
 ang. Froriep 
 
 N. hypoglossus 
 
 ng. nodos. 
 
 -N. desc. cerv. 
 "Rami hyoid. 
 (Ansa hypoglossi) 
 
 ~N. musculocutan. 
 N. axillaris 
 "N. phrenicus 
 -N. medianus 
 
 X. radialis 
 
 N. ulnaris 
 
 ITh. 
 
 Tubus digest.^' 
 
 N. femoralis 
 N. obturatorius 
 
 R. posterio 
 
 R. terminalis lateralis 
 R. terminalis anterior 
 Mesonephros 
 Nn. ilioing. et hypogastr. 
 
 FIG. 435. Lateral view of a reconstruction of a 10 mm. human embryo, showing the origin and 
 distribution of the peripheral nerves. The ganglionic masses are represented by darker and 
 the fiber bundles by lighter shading. For purposes of orientation the diaphragm and some 
 of the viscera are shown. The arm and leg are represented by transparent masses into the 
 substance of which the nerve branches may be followed. Streeter. 
 
498 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 masses. The changes taking place are similar to those exhibited in the 
 differentiation of the spinal nerves (p. 490). The central relations of the 
 nerves of this region of the medulla are shown in Fig. 436. (Comp. Fig. 407). 
 The glossopharyngeus at the same time develops its branches, most of the 
 peripheral fibers running in the third arch (lingual branch). Somewhat later 
 (12 to 14 mm. embryo) another bundle (tympanic branch) (Fig. 435) passes for- 
 ward to the second arch. This forms the typical branchiomeric arrangement 
 in which there is a forking of the nerve into prebranchial and postbranchial 
 branches, the latter being larger and containing the efferent element (see p. 464 
 and Fig. 405). 
 
 Roof plate 
 
 Alar plate 
 Fourth ventricle 
 
 Tractus solitarius 
 
 (in marginal layer) 
 
 Efferent nu. N. X. 
 Nucleus N. XII. - 
 
 Ganglion N. X. _J 
 
 Sulcus limitans 
 
 - Inner layer } 
 
 " Mantle layer } 
 
 of basal 
 plate 
 
 ~ Ventro-lat. column 
 (in marginal layer) 
 
 Floor plate 
 
 FIG. 436. Transverse section through the rhombic brain of a 10.2 mm. human embryo (during the 
 fifth week). X, Vagus; XII, Hypoglossus. His. 
 
 While the ganglia of the facialis and acusticus are derived from the same 
 mass of cells (p. 495, Fig. 434) and are later still in very close apposition, it must 
 be remembered that they are totally different in character. At four weeks they 
 are differentiated from each other (Fig. 437). The relations of the two ganglia 
 are shown in Figs. 435 and 437. It is probable that the ganglion of the facial 
 (geniculate ganglion) shows an early differentiation into dorsal and ventral 
 parts similar to the ganglia of the IX, and X, and also has associated placodes. 
 The peripheral branches of the cells of the geniculate ganglion develop into the 
 great superficial petrosal and chorda tympani. Both of these nerves enter into 
 secondary relations with the V. There is some doubt as to whether the chorda 
 is a prebranchial or postbranchial nerve (Fig. 435; also compare p. 462 and 
 Figs. 405 and 406). 
 
THE NERVOUS SYSTEM. 
 
 499 
 
 The VII, IX and X are, as already mentioned, branchial (splanchnic) 
 nerves and the central processes of their ganglia all have a common destina- 
 tion; they grow into the lateral surface of the medulla oblongata, enter the 
 marginal layer of the alar plate, and there bend caudally, forming a comrion 
 descending bundle of fibers in the marginal layer, the tractm solita.-ius 
 (Figs. 436 and 470; see also pp. 462, 465). 
 
 The acoustic ganglionic mass is elongated at an early stage, and is in c on- 
 r.ection with an ectodermal thickening (placode) which gives rise to the acoi stic 
 
 Roof plate 
 
 If"- Alar plate 
 
 Sulcus limitans 
 
 Basal plate 
 
 Floor plate 
 
 FIG. 437. Transverse section through the acoustic region of the rhombic brain of a 10.2 mm. human 
 embryo. VI, Abducens and its nucleus; VII G. g., geniculate ganglion; 77/7 G. c., cochlear 
 ganglion of acoustic nerve; VIIIG.v., vestibular ganglion of VIII nerve. His. 
 
 receptors (p. 591). From the upper part of the mass a bundle of peripheral 
 processes forms a branch which subsequently innervates the ampullae of the 
 superior and lateral semicircular canals and the utricle, while from the lower 
 part a branch develops to the ampulla of the posterior canal and to the saccule. 
 The nerve and ganglion (ganglion of Scar pa) is thus at first vestibular and at 
 this stage the cochlear part of the ear vesicle is not indicated as a separate out- 
 growth. As the lower border of the vesicle grows out into the cochlea, the 
 lower border of the ganglion becomes thickened and develops into the cochlear 
 ganglion (the ganglion spirale). It will be recalled that the vestibular part of 
 
500 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 the ear is the older part phylogenetically, the cochlea being a more recent special- 
 ized diverticulum of the older structure. (See p. 592 and Figs. 512 and 513.) 
 
 The central processes of the acoustic ganglionic mass first develop from the 
 upper part, forming the vestibular nerve root which enters the marginal layer of 
 the medulla. A portion at least of its fibers bends caudally, forming a de- 
 scending tract. The central processes of the cells of the cochlear ganglion, 
 forming the cochlear nerve root, pass dorsally, cross the vestibular ganglion and 
 enter the medulla dorsal and lateral to the vestibular root fibers (Fig. 437). 
 
 Roof plate 
 
 FIG. 438. Transverse section through the rhombic brain in the region of the trigeminus (V) nerve 
 of a 10.2 mm. human embryo, a. W., Spinal V; G.G., Gasserian ganglion; V.m., efferent 
 root of V nerve. His. 
 
 The trigeminus is the most anterior of the ganglionic masses (Fig. 434). 
 Embryological evidence has been brought to show that it consists of two or 
 more nerves which subsequently fuse. Placodes have also been described. 
 It is possible that such placodes represent those belonging to the most anterior 
 division of the lateral line system in lower forms, and probably in this case 
 would not properly belong to the V (comp. Fig. 405). From the ganglionic 
 mass (Gasserian or semilunar ganglion) the three principal branches oph- 
 thalmic, maxillary and mandibular are formed, the two latter passing into the 
 
THE NERVOUS SYSTEM. 
 
 501 
 
 Roof plate 
 
 Floor plate 
 
 FIG. 439. Transverse section through the trigeminal region of the rhombic brain of a 10.2 mrru 
 human embryo, a. W., Spinal V; V. s., Gasserian ganglion; V. m., part of efferent root of 
 V nerve. His. 
 
 FIG. 440. Part of a transverse section through -the rhombic brain of a chick embryo toward the 
 
 fourth day, showing the trigeminal roots. Cajal. 
 A, part of the efferent (masticator) nucleus of the V; B, efferent root of the V; C, bipolar cells of 
 
 the Gasserian ganglion; D, beginning of descending tract (spinal V) formed by the central 
 
 processes of C. 
 
502 TEXT-BOOK OF EMBRYOLOGY. 
 
 maxillary process and mandibular arch, respectively (Fig. 435). The central 
 processes, forming the afferent root (portio major] of the V, enter the marginal 
 layer of the alar plate of the rhombencephalon and form a descending bundle, 
 the' spinal V (Figs. 438, 439, 440 and 470). 
 
 The trigeminus exhibits its spinal-like character in the behavior of its 
 visceral portion (comp. p. 491). Cells of the ganglionic mass migrate further 
 peripherally and form sympathetic ganglia (ciliary, ode, spheno palatine (?) 
 submaxillary(?) ). As in the cord, the question has arisen whether efferent 
 roots may not also contribute a portion. Cells have been described as migrat- 
 ing with the oculomotor root fibers and forming part of the ciliary ganglion 
 (Carpenter). 
 
 Besides those already described (cerebrospinal, sympathetic), the only 
 other peripheral neurones of the nervous system are connected with the PROS- 
 ENCEPHALON and are a part of the eye and nose. The visual receptors (rods 
 and cones) and peripheral afferent neurones (bipolar cells) appear to be repre- 
 sented by portions of the retina and are described elsewhere (Chap. XVIII). 
 
 In the nose there is first a placode (p. 452) from which neuroblasts develop. 
 Some of these migrate toward the neural tube and probably differentiate into 
 lemmocytes, a few becoming ganglion cells.* The majority of the neuroblasts 
 remain in the olfactory epithelium, sending their axones (fila olfactoria) into 
 the olfactory bulb, the peripheral afferent olfactory neurones thus apparently 
 displaying the primitive ectodermal location of afferent peripheral neurones 
 (p. 448 and Fig. 397). (Comp. p. 584.) 
 
 Development of the Lower (Intersegmental) Intermediate Neurones. 
 
 It has already been seen how, by migration and by differentiation of the cells 
 during migration, the nucleated layer comprising the greater part of the thick- 
 ness of the wall of the neural tube is differentiated into two layers an inner 
 nucleated layer retaining its earlier characteristics, and an outer nucleated 
 (mantle) layer, composed largely of the differentiating neuroblasts and 
 characterized in ordinary staining by more widely separated nuclei. It has 
 also been seen that this differentiation takes place earlier and more rapidly at 
 first in the ventral part of the lateral walls (basal plate), and that the first cells to 
 migrate and differentiate are those whose axones grow out through the neural 
 wall and pass out as the ventral root fibers. 
 
 Not much later than the above differentiation of the efferent peripheral 
 neurones, axones of other neuroblasts also grow toward the periphery of the 
 tube but do not pass beyond its wall. Such neuroblasts become intermediate 
 
 * The latter are probably transient, but possibly in some forms persist as the ganglion cells of the 
 Jiervus terminalis of Pinkus. 
 
THE NERVOUS SYSTEM. 
 
 503 
 
 neurones (p. 449). The migrating bodies of these neuroblasts are checked at 
 the inner boundary of the marginal layer, but their growing axones enter the 
 marginal layer and there, apparently on account of their inability to penetrate 
 the external limiting membrane, turn cranially or caudally, or bifurcate, and 
 form longitudinal ascending and descending fibers. These longitudinal fibers 
 constitute a part of the future white columns (see p. 507) , and their cells are 
 therefore often called column cells. Many axones from such cells in all parts 
 of the lateral walls (Jteleromeric or commissural column cells) pursue a ven- 
 tral course through the mantle layer, arching around near the periphery and 
 
 FIG. 441. Part of a section through the lumbar spinal cord of a 76-hour chick embryo. Cajal. 
 A, Ventral root; 5, spinal ganglion; C, bifurcation of dorsal root fibers forming beginning of dorsal 
 funiculus; a, b, c, neuroblasts showing various stages of differentiation into intermediate 
 neurones, some, at least, (c) becoming heteromeric column cells; d, efferent neurone. 
 
 crossing the floor plate, ventral to the lumen, to become longitudinal ascending 
 and descending fibers in the marginal zone of the opposite side. These early 
 decussating axones form, in the cord, the beginning of the anterior commissure 
 (Fig. 441). Other neuroblasts, the axones of which do not cross the median 
 line, become tautomeric column cells. 
 
 It is about this time that the afferent root fibers enter the marginal layer of 
 the dorsal part (alar plate) of the lateral wall and form in the marginal layer 
 the various bundles of longitudinal fibers above described (dorsal funiculus, 
 tractus solitarius, descending vestibular, and spinal V) (Figs. 441, 442, 436, 437^ 
 
504 TEXT-BOOK OF EMBRYOLOGY. 
 
 439, 440 and 470). In the cord the ascending arms grow to a greater length 
 than the descending. In the rhombic brain the reverse is usually the case. 
 
 The longitudinal fibers of the afferent roots and of the intermediate neurones 
 thus form an external layer occupying the marginal layer of the neural tube. 
 This is the beginning of the differentiation into white and gray matter, i.e., 
 into that part of the neural tube containing only the axones of the neurones 
 and into that part containing the cell bodies and the beginnings and termina- 
 tions of the axones. The terminations of axones are formed by a turning of 
 the longitudinal fibers into the mantle layer or gray matter to form there 
 terminal arborizations. Later, the longitudinal fibers develop branches (col- 
 laterals) which also pass into the gray matter. The differentiation of the 
 white matter is completed several months later by the myelination of the 
 nerve fibers. 
 
 The longitudinal axones of intermediate neurones which are formed at this 
 period in the cord and epichordal brain are located ventrally near the median 
 line. These medial tracts occupy the position of the future medial longitu- 
 dinal fasciculi, the reticulo-spinal and ventral ground bundles, and may be 
 regarded on both comparative anatomical and embryological grounds as a 
 primitive system of long and short ascending and descending tracts mediating 
 between cerebrospinal afferent and efferent peripheral neurones, and not 
 having at this period connections with the higher centers. Other more lateral 
 tracts of this character are formed somewhat later, the whole forming the 
 beginning of the reticular formation + ventro-lateral ground bundle system 
 (compare Figs. 442, 449, 452 and 454). 
 
 While merging more or less imperceptibly into the following stages, it may 
 in a general way be said that at this stage of development there is differentiated 
 what might be termed the primary and probably the oldest coordinating mech- 
 anism of the nervous system, most clearly segmental in character and having 
 general features common not only to all Vertebrates, but to many Invertebrates. 
 It is characterized by afferent and efferent peripheral neurones arranged seg- 
 mentally and connected longitudinally in the central nervous system by crossed 
 and uncrossed intersegmental intermediate neurones. (Compare pp. 465 and 
 466) . At the anterior end of this part of the nervous system (epichordal segmen- 
 tal brain) there are also exhibited differentiations due to fundamental vertebrate 
 differentiations in the peripheral receptive and effective apparatus. Some of 
 these are: (i) The differentiation of the splanchnic (visceral) receptive and 
 motor apparatus, giving rise in the nervous system to (a) a separate system of 
 afferent root fibers (tractus solitarius) including the more specialized gustatory 
 apparatus; (b) a distinct series of lateral efferent nuclei. (2) The concentra- 
 tion of the non-specialized somatic afferent innervation into one nerve (tri- 
 
THE NERVOUS SYSTEM. 505 
 
 geminus and its central continuation, the spinal V). (3) The specialized 
 somatic sense organ, the ear, with its older vestibular and newer cochlear 
 divisions with central continuations of its nerves, including a vestibular 
 descending tract. 
 
 These differentiations of the peripheral afferent apparatus lead to the later 
 formation of special terminal nuclei for their central continuations and second- 
 ary tracts from these nuclei to suprasegmental structures (p. 466, Fig. 409). 
 
 The peripheral and intermediate neurones of the more highly modified 
 cranial end of the tube, or FORE- BRAIN, appear to lag behind in development, 
 but in its basal part the neuroblasts are beginning to be differentiated (fifth 
 week). In the development of the eye, the brain wall is evaginated, carrying 
 with it the future retina comprising, apparently, the sensory epithelial cells or 
 receptors (rods and cones), the afferent peripheral neurones (bipolar cells of 
 retina) and the receptive or primary intermediate neurones (ganglion cells of 
 retina and optic nerve). The histogenesis of these elements is dealt with 
 elsewhere, but it may be pointed out here that the axones of the ganglion 
 cells of the retina grow toward the inner side of the optic cup (away from 
 the original luminal surface), pass thence in the marginal layer of the optic 
 stalk, undergo a partial ventral decussation (optic chiasma) in the floor plate, 
 and terminate in certain thalamic nuclei (lateral geniculate bodies) and in the 
 roof of the mid-brain. The so-called optic nerve is thus obviously a central, 
 secondary tract. The development of this tract does not apparently take place 
 until a later period than the differentiation of the earlier secondary tracts of the 
 cord and rhombic brain (after the sixth week). 
 
 In the case of the olfactory organ, it has already been seen that the peripheral 
 neurones develop at first apart from the neural tube and send their axones 
 into the olfactory bulb. The latter is an evagination of the neural tube 
 which receives the olfactory fibers, thereby constituting a complicated terminal 
 nucleus for the latter. The axones of bulb cells (the mitral cells} which pass 
 along the stalk of the bulb are thus the secondary tract of this system. Many 
 of them decussate in the anterior commissure. Secondary (and tertiary) 
 olfactory tracts find their way to caudal parts of the rhinencephalon and to 
 hypothalamus, thalamus and epithalamus, forming, with other tracts, a highly 
 modified prechordal intersegmental mechanism (p. 537). Other olfactory tracts 
 proceed to the suprasegmental archipallium which develops efferent bundles 
 to the segmental brain. 
 
 The embryological development of the peripheral apparatus, especially 
 of its receptive portions, as shown by the various separate ganglionic rudiments 
 (Fig. 434) and placodes, exhibits a segmental character which, though not 
 in all respects primitive, is of practical value. These segments are (Adolf 
 Meyer): (i) The olfactory apparatus, nose, without efferent elements. (2) 
 
506 TEXT-BOOK OF EMBRYOLOGY. 
 
 The visual apparatus, eye, with the eye-moving III and IV mid-brain nerves 
 as its efferent portion. (3) The general sensory apparatus of the surfaces of 
 the head and mouth, the afferent trigeminus, with the jaw-moving efferent 
 trigeminus. (4) The auditory (and vestibular) apparatus, the ear (VIII 
 nerve) , with the VI (turning the eye to the source of sound) and VII (ear and 
 face muscles) efferent nerves. In the latter, the original ear-moving appa- 
 ratus has been replaced largely, in man, by the muscles of expression. (5) 
 The visceral segment (IX, X, and XII nerves), not indicated externally in 
 forms without gills. The afferent portion is concerned with taste and visceral 
 stimuli, the efferent with tasting, swallowing, sound-production and other 
 visceral functions. Overlapping with other segments is due to its visceral as 
 opposed their somatic character. The apparent dislocation shown by the 
 abducens is due to its common use by more than one segment. 
 
 Caudal to this is the mechanism for head movement (N. XI), its afferent 
 portion being the upper spinal nerves. Following this, there is the segmental 
 series of spinal nerves which in places shows a tendency to fuse (plexuses) into 
 larger segments (phrenic segment, limb segments) . All such modifications are 
 expressions of more recent functional adjustments modifying preexisting ones. 
 
 These segments may be regarded as a series of reflex arcs, each one of 
 which may have a certain amount of physiological independence but which 
 are associated by intersegmental neurones. The latter class of intermediate 
 neurones probably effects certain groupings of various efferent neurones, fur- 
 nishing mechanisms which secure harmonious responses of groups of effectors 
 involved in certain definite reactions (e.g., limb-movements, associated eye 
 movements). These effector-associating mechanisms may be acted on di- 
 rectly (reflex) by afferent neurones or by the efferent arms of suprasegmental 
 mechanisms. 
 
 Superadded to this segmental apparatus are the suprasegmental mechan- 
 isms which develop later, the pallium being the last to be completed. These 
 receive bundles from the segmental nervous system and send descending 
 bundles to the intersegmental neurones (pp. 457, 465 and 466 and Fig. 409). 
 
 FURTHER DIFFERENTIATION OF THE NEURAL TUBE. 
 The Spinal Cord. 
 
 From this time on, differences of structure between cord and epichordal 
 segmental brain become more marked and make it more convenient to treat 
 their later development separately. The ventral half of the cord for a con- 
 siderable period maintains its lead in development. At four weeks (Fig. 442) 
 this lead is not so pronounced as in the immediately following period. At 
 this stage it will be noticed that the lumen is narrower in the ventral part, 
 
THE NERVOUS SYSTEM. 
 
 507 
 
 as if due to the greater thickening of the ventral walls (basal plates). The 
 increase of the mantle layer (gray) of the basal plate marks the beginning of 
 the ventral (anterior) gray column or horn. The increase in the basal plate 
 may be partly due to neuroblasts migrating from the alar plate. These 
 would be intermediate neurones. The development of the mantle layer at 
 the expense of the inner layer, due to differentiation and migration of the cells 
 of the latter, is well shown, but is more marked in the following stages. 
 
 As already mentioned, the axones of the heteromeric cells, many of which 
 lie in the dorsal half of the lateral walls, after decussating (anterior commis- 
 
 Beginning of 
 dorsal funiculu 
 
 Dorsal root 
 
 Mantle layer'' 
 
 Ventral root 
 
 (from neuroblasts 
 
 of mantle layer) 
 
 FIG. 442. Half of a transverse section of the spinal cord of a 4 weeks, (6.9 mm.) human embryo. 
 Dp, Roof plate; Bp, floor plate. His. 
 
 sure), form longitudinal fibers in the marginal layer along the ventral surface 
 of the opposite side, mostly mesial to the emerging ventral roots (Fig. 442). 
 These longitudinal fibers are the beginning of the ventral (anterior) white columns 
 or funiculi of the cord. The sides of the tube between the dorsal and ventral 
 roots contain at first only a few longitudinal fibers the beginning of the ventro- 
 lateral funiculi. Their number soon rapidly increases, the fibers apparently 
 coming from ventrally located tautomeric cells. The dorsal root fibers, as 
 stated before (p. 490), form small round bundles in the marginal layer of the 
 dorsal halves (Fig. 442). This is the beginning of the dorsal (posterior) white 
 columns or funiculi. 
 
508 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 At four weeks there are blood vessels in the mesodermal tissue surrounding 
 the neural tube. Branches of these soon penetrate the tube itself. 
 
 From its first appearance in the cord as an oval bundle, during the fourth 
 week, the dorsal funiculus steadily increases in size, forming a "root zone" in 
 the marginal layer of the dorsal half, but not reaching the roof plate (Fig. 443). 
 This increase in size is probably produced in part by the addition on its 
 inner side of overlapping ascending arms of dorsal root fibers from lower 
 
 Partly differentiated mantle layer 
 Mantle layer 
 
 Dorsal funiculus 
 (post, white column) 
 
 Dorsal root 
 
 Marginal furrow 
 Dorsal spinal artery/ 
 
 Arcuate fibers- 
 
 Cylinder furrow--; 
 
 Lateral gray^ 
 column (lat. horn) 
 
 Meningeal 
 membrane 
 
 Dp. 
 
 Ventral root ^ 
 
 FIG. 443. Half of a transverse section of the spinal cord of a 4^ weeks (10.9 mm.) human embryo. His. 
 A.s., Artery in ventral longitudinal sulcus; A.sp.a., ventral (anterior) spinal artery; Bp, floor plate; 
 Dp, roof plate; 7. /., inner layer. The faint inner outline is the outline of the cord proper. 
 
 cord segments. The mantle layer of this part contains an increasing number 
 of cells forming curved or arcuate fibers. (Fig. 443.) The increase in the 
 mantle cells of the dorsal part marks the beginning of the dorsal (posterior) 
 gray column or horn (terminal nucleus of the dorsal root fibers). Later, other 
 cells become differentiated from the inner layer which do not apparently form 
 arcuate fibers (Fig. 443) and which subsequently become part of the posterior 
 horn. It is possible that the axones of some of these cells form the compara- 
 
THE NERVOUS SYSTEM. 
 
 509 
 
 tively small ground bundles of the dorsal funiculus. During this period 
 of development of the dorsal portions of the lateral walls the latter have ap- 
 proached each other, reducing the dorsal part of the lumen to a slit. The 
 roof plate has undergone a slight infolding (Fig. 444). Ventral to the dorsal 
 roots there is a groove running along each side of the cord (marginal furrow of 
 His). At four and one-half weeks the number of fibers of the ventro-lateral 
 funiculus has greatly increased and another groove has appeared parallel and 
 ventral to the marginal furrow and forming the dorsal boundary of the ventro- 
 
 Intermediate plate 
 Central canal 
 
 Floor plate - - 
 
 Vent. long, sulcus 
 
 Dors, funiculus 
 
 Dors, gray column (post, horn) 
 
 Dors, root 
 Marginal furrow 
 Cylinder furrow 
 
 Lat. gray column (lat. horn) 
 Ventro-lat. funiculus 
 
 Vent, gray column (ant. horn) 
 Vent, root 
 
 Vent, funiculus 
 (ant. white column) 
 
 Vent. sp. artery 
 
 FIG. 444. Half of a transverse section of the spinal cord of a human embryo 
 of 18.5 mm. (7^ weeks). His. 
 
 lateral funiculus (cylinder furrow of His) (Figs. 443 and 444). The portion 
 of the lateral wall lying between these two grooves or furrows forms an 
 intermediate plate which contains few fibers in its marginal layer at this 
 period, and is thus backward in development. Grooves appear on the luminal 
 wall, apparently corresponding approximately to the outer grooves. 
 
 The further growth of the dorsal funiculi and the concomitant growth 
 of the associated gray matter, i.e., of the cells of the adjoining mantle layer, 
 proceed until we have the conditions shown in Figs. 444 and 445. At the 
 same time there is a further approximation of the dorsal portions of the lateral 
 
510 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 walls so that the widest part of the lumen is further ventral. At about eight 
 weeks the portion of the wall near the median line, which has formed a ridge 
 by the apposition of the two inner layers and the roof plate (Fig. 444 Y), and is 
 uncovered as yet with fibers, differentiates a marginal layer (eight and one-half 
 weeks, Fig. 445) into which fibers grow forming, on each side, in the upper 
 part of the cord, the column of Goll or fasciculus gracilis (Fig. 446). Many 
 of these fibers, at least, are the ascending arms of caudal dorsal root fibers, 
 which are thus added mesially to the continuations of upper cord roots. It will 
 
 Rudiment of funiculus gracilis 
 
 Dorsal funiculus (cuneatus) 
 
 Intermediate plate 
 
 Central canal 
 
 Floor plate - 
 Vent. long, sulcus - 
 
 Dors, gray column 
 
 - -. Dors, root 
 
 Marginal furrow 
 Cylinder furrow 
 
 Lat. gray column 
 
 Ventro-lat. funiculus 
 
 Vent, gray column 
 
 Vent, root 
 Vent, funiculus 
 
 Vent. sp. art. 
 
 FIG. 445. Half of a transverse section of the spinal cord of a human embryo of 
 24 mm. (8| weeks). His. 
 
 be noted that there is now a massive dorsal gray column and that the original 
 oval bundle has extended around on the mesial side of this gray column. 
 
 While these changes are taking place, the dorsal portions of the lateral walls 
 have fused, probably beginning at the most dorsal part, thus forming the dorsal 
 septum. This may be accompanied by a certain amount of rolling in from the 
 dorsal part indicated by the direction of the ependyma cells (Fig. 445) . The 
 growth of the ventral funiculi and gray columns results in the appearance 
 and subsequent increasing depth of the ventral longitudinal fissure. The cord 
 now resembles the adult cord in many features, having well-marked white* and 
 
 *The term "white " column is used for convenience. The funiculi do not become "white" until 
 their fibers become myelinated during the sixth month. 
 
THE NERVOUS SYSTEM. 
 
 511 
 
 gray columns, but contains a disproportionately small amount of fibers. A 
 further and later change consists in a rolling inward, as it were, of the dorsal 
 gray column so that it becomes separated from the ventral gray column, and 
 that portion of it formerly facing dorsally comes to face more mesially, the roots 
 entering more dorsally. This change may be due partly to the development 
 of the intermediate plate which has in the meantime taken place. In this 
 plate axones of tautomeric cells have begun to form the limiting layer of the 
 lateral funiculus. From the cells of the intermediate plate are formed the 
 neck of the dorsal gray column, also the cells of Clarke's column and the 
 
 Funiculus gracilis 
 
 Dors, funiculus (cuneatus) 
 Dors, gray column 
 Dors, root 
 
 Marginal furrow 
 
 -\ Intermed. plate 
 
 Cylinder furrow 
 
 !\"|~ ~" Lat. gray column 
 
 - - - Ventro-lat. funiculus 
 Vent, gray column 
 
 - Vent, root 
 
 Vent, funiculus 
 Vent. sp. artery 
 FIG. 446. Half of a transverse section of the spinal cord of a human foetus of about 3 months. His. 
 
 processus reticularis. In the course of these developments, the ventro-lateral 
 ground bundles, formed primarily by heteromeric and tautomeric cord cells, 
 receives various accessions. These are first the long descending inter- 
 segmental tracts from epichordal brain nuclei in the formatio reticularis 
 which as they proceed down the cord naturally overlap externally the ground 
 bundles already formed there. They include the medial longitudinal jasciculi, 
 tracts from Deiters 1 nuclei and the rubro-spinal tracts which occupy the ventro- 
 lateral funiculi external to the ground bundles. In the lateral funiculi there 
 are also added the ascending tracts from cord nuclei to suprasegmental structures. 
 
 ;*W ' ; .'.<- S>- .. .' : C'*." 5 ~.- 
 
512 TEXT-BOOK OF EMBRYOLOGY. 
 
 These are the dorsal spino-cerebellar tracts from Clarke's columns, ventral spino- 
 cerebellar tracts, and tracts to mid-brain roof and thalamus (spino-tectal and 
 thalamic). Finally (fifth month) the descending tracts from the pallium are 
 added, the direct and crossed cortico- spinal (pallio-spinal or pyramidal] tracts, 
 the latter being thrust, as it were, into the lateral funiculus. 
 
 The development of the cord, then, is produced by (i) the proliferation of 
 the .epithelial cells and the formation of the nuclear and marginal layers ; (2) 
 the multiplication, differentiation and growth of the neuroblasts (mantle layer) ; 
 (3) the development of the ventral roots; (4) formation of the funiculi (white 
 columns when myelinated) by the growth into the marginal layer of (a) dorsal 
 root fibers of the cord, the ascending arms of which overlap those root fibres 
 entering higher cord segments, (b) cord neuroblasts forming intersegmental 
 (ground bundle) tracts next to the gray matter, (c) descending intersegmental 
 tracts from the segmental brain, representing continuations principally of cere- 
 bellar efferent tracts, (d) afferent suprasegmental tracts from cord nuclei, 
 (e) descending pallio-spinal tracts. In addition to this, there are general 
 factors of growth, such as increasing vascularization, increasing amount of 
 neurone cytoplasm (especially dendrites) , increased size of axones and, finally, 
 the acquisition by the latter of myelin sheaths. 
 
 The vertebral column grows faster in length than the inclosed spinal cord. 
 The result of this is that the caudal spinal nerves making their exit through the 
 intervertebral foramina are, so to speak, dragged caudalward and instead of 
 proceeding outward at right angle to the cord, pass caudally to reach their 
 foramina. The leash of nerve roots thus formed, lying within the caudal part 
 of the vertebral column, constitutes the cauda equina. The coverings of the 
 cord retain their original connections at the caudal end of the vertebral canal 
 and form a prolongation of the cord membranes enclosing the thin, terminal 
 part of the cord, the filum terminate. 
 
 The Epichordal Segmental Brain. 
 
 In the fifth week, the walls of the rhombencephalon are comparatively thin. 
 In the caudal region of the medulla oblongata (p. 477), the dorsal part of each 
 lateral wall is upright and is bent at a considerable angle with the ventral 
 part (basal plate), the groove on the inner surface between the two being the 
 sulcus limitans. The roof of this region is formed by the thin expanded roof 
 plate (Figs. 436-439)- 
 
 Anterior to this, the roof plate is not expanded, the alar plates almost 
 meeting in the mid-dorsal line. This thicker part of the roof is the rudiment 
 of the cerebellum. Its caudal edges are attached to the expanded roof plate (see 
 P- 525). 
 
THE NERVOUS SYSTEM. 513 
 
 In front of the cerebellum the tube is narrower and is compressed laterally. 
 This part is the isthmus (Fig. 447). Anterior to this, the roof plate and alar 
 plates expand into the mid-brain roof, the basal and floor plates forming the 
 basal part of the mid-brain. 
 
 Certain gross changes which from now on take place in the medulla riay 
 conveniently be noted here. At about this time (fifth week) the outer borders 
 of the alar plate become folded outward and then downward, being thus turned 
 back on the plate itself (Figs. 452 and 416). This fold is called the prhwry 
 rhombic lip, and is most marked along the caudal border of the cerebellum. 
 The folds of the lip then fuse, forming a rounded eminence composing the border 
 of the alar plate to which the roof plate is attached laterally. Subsequently, 
 the attachment to the roof plate is shifted dorsally in the medulla, caudally in 
 
 D.IV 
 
 Nu. IV. 
 
 FIG. 447. Transverse section through the isthmus of a 10.2 mm. human embryo. D.IV, Decussa- 
 tion of trochlear nerve; M. /., marginal layer; Nu. IV, nucleus trochlear nerve. His. 
 
 the cerebellum. The portion of this lip which thins off into the roof plate is the 
 tcenia of the medulla and the posterior velum and taenia of the cerebellum. The 
 thin roof plate itself becomes tbe epithelial part of the tela chorioidea of the 
 fourth ventricle. At the caudal apex of the fourth ventricle a fusion of the 
 lips of the opposite sides forms the obeoc. 
 
 A further complication is due to the increasing pontine flexure by which the 
 dorsal walls of the tube are brought close together (Fig. 448). The transverse 
 fold of the tela thus produced is the chorioid fold. At about the same time 
 lateral pocketings outward of the dorsal w r alls occur just caudal to the cere- 
 bellum which contain portions of the chorioid fold. These are the lateral 
 recesses. By further growth and vascularization, the mesodermal part of the 
 chorioid fold forms the chorioid plexus of the fourth ventricle (metaplexus). 
 Finally, in the human brain an aperture appears in the caudal portion of 
 the roof of the ventricle the foramen of Magendie (metapore) ; and, according 
 to many authorities, one also occurs in the roof of each of the lateral recesses 
 
514 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 the foramina of Luschka. The roof of the fourth ventricle, where present, 
 is thus composed of an inner ependymal epithelium the expanded roof plate 
 of the neural tube and an outer mesodermal covering containing blood vessels. 
 Other gross changes chiefly involve the basal plate. At the beginning of the 
 fifth week this does not much exceed the alar plate in thickness and is separated 
 from the opposite basal plate by an inner median sulcus (Fig. 452). The basal 
 plate now increases in thickness and thereby both deepens the sulcus and con- 
 tributes to a flattening out of the lateral walls, so that all portions by the sixth 
 week lie approximately in the same horizontal plane (Fig. 454). Later, the 
 floor plate increases in thickness more rapidly and the sulcus becomes shallower 
 (eight weeks) (Fig. 455). The band of vertical ependyma fibers passing through 
 
 Mesencephaion 
 
 Epiphysis 
 Diencephalon 
 
 Isthmus 
 
 Cerebellum 
 Transverse fold 
 - -Rhombic lip 
 
 Olfactory lobe 
 Optic stalk 
 
 Infundibulum Hypophysis 
 FIG. 448. Lateral view of a model of the brain of a 
 
 , 
 
 Basilar artery 
 
 weeks' (18.5 mm.) human embryo. His. 
 
 it is the septum medulla. It is bounded on each side by a vertical extension of 
 the marginal layer which for convenience will be referred to as the septal 
 marginal layer (Figs. 453, 454 and 455). 
 
 The histological condition of this part of the tube at the beginning of five 
 weeks has already been described. The lateral walls consist of an inner layer 
 of closely packed cells, of a mantle layer consisting of efferent neurones and a 
 simple system of intermediate neurones, and an outer marginal layer containing 
 the longitudinal bundles of incoming afferent roots and longitudinal axones of 
 intermediate neurones (see p. 504). It has been seen that this condition has 
 been brought about by the proliferation of cells near the tube cavity, which 
 migrate outward, at the same time many of them differentiating into neuro- 
 blasts and nerve cells and thereby forming the mantle layer. As in the cord, 
 the basal plate takes the lead and thus at first outstrips the alar plate, as shown 
 
THE NERVOUS SYSTEM. 515 
 
 in its greater thickness above mentioned. This process likewise terminates 
 sooner in the basal plate, few cell divisions being present there at seven weeks. 
 At about the end of the fifth week (see p. 519) the alar plate begins to develop 
 very rapidly. Its period of proliferation is about terminated at the end of the 
 second month. When the cell proliferation near the ventricle has ceased, 
 the inner layer is reduced by outward migration to a single layer of epend] ma 
 cells (compare pp. 485 and 486). 
 
 While the efferent nuclei continue to develop and the central continuations 
 of the afferent neurones continue to grow in length, the principal differential ions 
 now taking place in the rhombic brain are those affecting the intermediate 
 neurone systems. 
 
 The first of these to be considered is the further differentiation of the system 
 of intersegmental neurones (p. 465). The earlier development of this system 
 has been seen to involve especially the basal plate and the further development 
 of the latter leads to the complete differentiation of the formatio reticularis 
 which especially represents this system in the epichordal brain. It has already 
 been seen (p. 504) that many of the intermediate neurones representing the 
 beginning of this system seem to be at first : Jieteromeric and form an internal 
 arcuate system of fibers similar to those seen in the cord (pp. 503, 507). They 
 increase in number toward the median line and are especially numerous in the 
 basal plate, where they, together with the medial efferent neurones (XII and 
 VI cranial nerves) , form an eminence of the mantle layer corresponding to the 
 ventral gray column of the cord (Fig. 449) . Many of the axones of these cells 
 of the arcuate system cross the septum medullae, thus marking the beginning of 
 the raphe, and form on each side a longitudinal bundle in the septal marginal 
 layer (Fig. 449). These longitudinal bundles correspond to the first formation 
 of the ventral funiculi of the cord. They must not, of course, be confused 
 with the pyramids which appear much later. Whether these longitudinal 
 bundles are also partly formed of axones of tautomeric cells is uncertain. 
 Later, as the anterior horn swellings grow and the depth of the septum 
 medullae and of the septal marginal layers increases (compare p. 514), more 
 longitudinal fibers appear in the latter, the new ones apparently being added 
 ventrally. Others also appear more laterally in the marginal layer (Figs. 453, 
 454 and 455). (Compare cord, p. 507.) At this time, also, fibers enter the 
 marginal layer bordering the surface (as distinguished from the septal), pass 
 along parallel with the surface, cross the septum, and proceed to various parts 
 of the marginal layer of the opposite side. These fibers are the first external 
 arcuate fibers as opposed to the preceding internal arcuate fibers which traverse 
 the mantle layer (gray) in the arcuate part of their course (Fig. 453). 
 
 The majority of the longitudinal fibers entering the septal marginal layers 
 during the second month occupy approximately the position of the future 
 
516 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 mesial formatio reticularis alba (white reticular formation) and correspond in 
 position to the fibers of the medial longitudinal fasciculi and reticulo- spinal 
 tracts in the adult medulla, representing probably the same system as the 
 medial part of the ventro-lateral funiculi of the cord (medial longitudinal 
 fasciculi, reticulo-spinal and ventro-medial ground bundles of the cord) . The 
 medial longitudinal fasciculi are in part descending fibers from higher levels 
 described later. 
 
 Taenia 
 
 Marginal layer 
 Mantle layer 
 
 Alar plate 
 
 Sulcus limitans 
 
 Basal plate 
 
 Inner la 
 
 Tractus solitarius 
 
 N. X. 
 (Medullary XI) 
 
 Internal arcuate fibers 
 
 (in beginning gray 
 
 reticular formation) 
 
 N. XII 
 
 Ventral funiculus Floor plate 
 
 (beginning of form, retic. alba) 
 
 FIG. 449. Half of a transverse section of the medulla of a 10.2 mm. human embryo. His. 
 
 In the basal plate, between the medial and lateral efferent nuclei, there are, 
 even at the beginning of the fifth week, not only the efferent neurones and the 
 heteromeric (commissural) neurones already mentioned, but other neuroblasts 
 whose axones have a radial direction, i.e., toward the periphery. (Figs. 449 
 and 452.) The interlacing of these with the arcuate fibers forms the first 
 indication of the formatio reticularis grisea (gray reticular formation) . Later, 
 longitudinal fibers are present here, giving rise to a condition more fully 
 corresponding to that in the adult, analogous also to the condition in the 
 lateral funiculi of the cord, especially in the processus reticularis. 
 
THE NERVOUS SYSTEM. 
 
 517 
 
 In the region of the auditory segment an important neurone group appears 
 which is possibly a differentiation of the extreme dorso-lateral portion of the 
 basal plate. This is Deiters^ nucleus, which apparently receives vestibu'ar 
 and cerebellar fibers and sends uncrossed descending bundles along the outer 
 later?,! part of the reticular formation and also ascending and descending crossed 
 and uncrossed fibers along its outer mesial portion (part of the medial Icngi- 
 tudiial fasciculus). This nucleus thus represents, apparently, like the nucleus 
 rubar and nucleus of Darkschewitsch (below), a differentiated portion of the 
 int ;rsegmental neurones in especial connection with suprasegmental efferent 
 fibers which thereby act on many brain and cord segments. 
 
 The great development of the reticular formation here and caudally possibly 
 causes a ventro-lateral displacement of the contained nucleus ambiguus and 
 efferent facial nucleus and consequently the arched or hook-shaped course of 
 
 Germ facialis 
 
 medsulcus 
 
 B 
 
 medsiilcus 
 
 FIG. 450. Diagram illustrating the development of the genu of the facial nerve in the human 
 embryo. The drawings show the right facial nerve and its nucleus of origin, in three stages: 
 the youngest, A, being a 10 mm. embryo, and the oldest, C, a new-born child. The relative 
 position of the abducens (VI) nerve is represented in outline; its nerve trunk is not shown, as 
 the structures represented are seen from above. Streeter. 
 
 their root fibers as seen in transverse section (Streeter) . At the same time, the 
 nucleus of the VI, which originally was caudal to the VII, migrates cranially, 
 carrying the facial efferent roots with it. This gives rise to the genu facialis 
 (Streeter, Fig. 450). 
 
 In the mid-brain (Fig. 451), what appears to represent the basal plate 
 forms an eminence, the tegmental swelling. Later there is differentiated from 
 this the reticular formation of this region, containing various nuclei and 
 traversed by radial, longitudinal and arcuate fibers, many of the latter arising 
 from the later differentiating dorsal portions (corpora quadrigemina) of the 
 lateral mid-brain walls. An important neurone group of the reticular forma- 
 tion system which appears in this region is the nucleus of Darkschewitsch. Its 
 descending axones form a part of the medial longitudinal fasciculus and 
 probably appear at the end of the first month. The nucleus ruber is probably 
 differentiated from the forward extremity of the tegmental swelling which over- 
 laps into a prechordal region (Fig. 463). Its axones (crossing asForersdecus- 
 sation and forming the rubro-spinal tract) probably develop early. This 
 
518 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 neurone group apparently owes its great development principally to its close 
 association with the cerebellum. These two long descending intersegmental 
 tracts as they grow downward envelop the differentiating reticular formation 
 of more caudal regions of brain (and cord) and thereby come to occupy an 
 external position in the fully differentiated reticular formation. 
 
 The reticular formation is thus composed of a gray portion containing the 
 neurone bodies and shorter tracts and a white portion composed of the longer 
 tracts. Axones from certain nuclei (especially N. ruber, N. of Darkschewitsch 
 and N. of Deiters) form long, principally descending, tracts which envelop the 
 gray reticular formation mesially (medial longitudinal fasciculus including 
 fibers from nuclei of Darkschewitsch and Deiters as well as other reticulo- 
 spinal fibers) and laterally (rubro-spinal, lateral uncrossed tract from Deiters' 
 
 -Alar plate 
 
 <^p*| '."'.,'*;" Marginal layer 
 
 > ^% "^ =.- - ^-C^^l 
 
 x %k~ -viiKi^-- NucIeusN - m 
 
 I Root^N.m 
 
 FIG. 451. Transverse section through the mid-brain of a 10.2 mm. human embryo. His. 
 
 nucleus and other reticulo-spinal fibers) and constitute the white reticular 
 formation. These long tracts descend to the cord and there similarly envelop 
 its ventro-lateral ground bundles. 
 
 While the above differentiation of the reticular formation has been taking 
 place, changes in the alar plate have begun which lead to the formation of 
 terminal nuclei of peripheral afferent nerves, as well as terminal nuclei of other 
 tracts, all of which send fiber bundles to suprasegmental structures. 
 
 The formation of the receptive nuclei of the afferent nerves of peripheral 
 (segmental) structures is complicated by the fact that the central continuations 
 of the peripheral afferent nerves are not confined to their own respective seg- 
 ments but form longitudinal tracts which continue to grow upward (columns of 
 Goll and Burdach) or downward (descending solitary, vestibular and trigeminal 
 tracts) passing into other segments and overlapping externally structures 
 already in process of formation there. In each segment, then, the terminal 
 nuclei of the afferent nerves of that segment must be distinguished from the 
 
THE NERVOUS SYSTEM. 519 
 
 terminal nuclei of afferent elements from other segments. The latter are 
 external or added to the former and are differentiated from additional prolifer- 
 ations of neuroblasts of the alar plate. In addition to these nuclei, there are 
 certain nuclei forming links between the two great suprasegmental structures, 
 the pallium and cerebellum. These nuclei are the olive* and pons nuclei, 
 both of which form afferent cerebellar bundles and which are differentiatec by 
 still further proliferations and migrations of alar plate neuroblasts. 
 
 It has already been seen that the afferent peripheral nerves (IX and X) 
 c-f the visceral segment form (together with descending fibers of the VII) the 
 tractus solitarius. This is at first (5th week) short, but in six weeks has rea :hed 
 the cord. The terminal nucleus of the tractus solitarius is differentiated irom 
 the neuroblasts of the medial portion of the alar plate. The course of the 
 axones of this nucleus is not known. Judging from comparative anatomical 
 grounds, they would not follow the fillet pathway (C. J. Herrick). The most 
 caudal part of this nucleus is the nucleus commissuralis at the lower apex of the 
 fourth ventricle. 
 
 The formation of the other terminal nuclei lying in the region of this seg- 
 ment is begun by the further developments of the alar plate already alluded 
 to. These are initiated by an expansion and consequent folding of its border 
 (formation of the rhombic lip, p. 513), followed by further cell-proliferation, 
 leading to fusion of these folds and copious formation of neuroblasts in this 
 region. These neuroblasts represent fresh accessions to the neuroblasts 
 already formed in the mantle layer of the more medial part of the alar plate. 
 This latest development of the border portions of the alar plate is the last step 
 in the progressive development of the neural tube from the medial portion 
 (basal plate) to the lateral (dorsal) border of the lateral walls of the tube 
 where further development ceases at the attachment to the roof plate (teenia). 
 (Fig. 45 2 -) 
 
 Many of the neuroblasts of the rhombic lip region migrate ventrally.t 
 Some of those from the medial part of the swelling produced by the fusion of 
 the rhombic lip folds (p. 513) migrate along the inner side of the tractus soli- 
 tarius, while those from the lateral part of the swelling pass outside the tractus, 
 which becomes thereby enclosed in the mantle layer (Fig. 453). Many of these 
 neuroblasts continue their journey, passing along the outer side of the differ- 
 
 * This is conjectural. The origin of fibers to the inferior olivary nuclei is not known. The 
 most conspicuous tract to the olive is von Bechterew's central tegmental tract. Purely a priori con- 
 siderations might be adduced in favor of this being considered a descending tract from thalamic 
 nuclei which in turn receive pallio-thalamic fibers. It may, however, arise from lower optic centers. 
 
 fit is, perhaps, an open 'question whether the formation of the lip is a fundamental feature in 
 this last proliferation and invasion of neuroblasts from the border of the alar plate. The promi- 
 nence of the rhombic lip in man is the early embryological expression of the future great develop- 
 ment of parts subsequently formed from this portion of the neural wall, especially the cerebellum 
 and neurone groups in connection with it. 
 
520 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 entiating formatio reticularis, until they are arrested at the septal marginal layer 
 (Figs. 454 and 455). 
 
 From these neuroblasts which remain in situ near the dorsal border are de- 
 veloped the nucleus gracilis and nucleus cuneatus. The axones of these nuclei 
 form internal arcuate fibers which decussate and form a bundle of longitudinal 
 fibers in the opposite septal marginal layer ventral to the reticularis alba. 
 This tract is the medial fillet whose fibers appear during the second month 
 and is one of the afferent paths to suprasegmental structures (mid-brain roof 
 
 Inner rhombic furrow 
 
 Rhombic lip 
 Outer rhombic furrow 
 Alar plate] 
 Sulcus limitans 
 
 Tractus solitarius 
 Inner layer 
 
 N. X (medullary XI) 
 Mantle layer 
 Marginal layer 
 
 Basal plate 
 
 Beginning of gray 
 reticular formation 
 
 Floor plate F.r.a. N. XII Internal arcuate fibers 
 
 (forming septum medullas) 
 
 FIG. 452. Half of a transverse section of the medulla of a 9.1 mm. human embryo 
 
 (during the fifth week). His. 
 The 'arrow is in the inner median sulcus. F. r. a., beginning of white reticular formation. 
 
 and pallium). Other neuroblasts, which probably migrate further, form the 
 substantia gelatinosa of Rolando. Axones of this group also form tracts repre- 
 senting afferent paths to suprasegmental structures (pallium). Neuroblasts 
 which migrate further form, as already mentioned, afferent cerebellar con- 
 nections. Those migrating to the septal marginal layer form there an 
 L-shaped mass mesial to the root fibers of the XII cranial nerve (Fig. 455). 
 This is the medial accessory olive. Fresh groups of neuroblasts, added laterally 
 to these in streaks, form the inferior olivary nucleus, while others which have not 
 advanced so far form the lateral nucleus. Axones of the olivary neuroblasts 
 
THE NERVOUS SYSTEM. 
 
 521 
 
 (olivo-cerebellar fibers) pass across the median line (seventh or eighth week) to 
 the opposite dorsal border where they, together with axones from the lateral 
 nuclei and the continuation from the cord of Flechsig's tract, form (end of 
 the second month) the bulk of the restiform body (Fig. 455). At three months 
 the olives have acquired their characteristic folded appearance. 
 
 Owing to the later development and ventral migration of the alar plate 
 r.euroblasts, there are thus formed the various nuclei which lie external to the 
 i^ticular formation in the adult. The continuations of ascending spinal >:ord 
 
 Outer part of rhombic 
 lip migration 
 
 Inner part of r. 1. mig. 
 Inner layer 
 Tractus solitarius 
 Marginal layer 
 Mantle layer 
 
 Ext. arcuate fibers 
 Int. arcuate fibers 
 
 Septum Beginning white N. XII Gray reticular 
 medullae reticular formation formation 
 
 FIG. 453. Half of a transverse section of the medulla of a 10.5 mm. human embryo 
 (end of fifth week). His. 
 
 tracts (Flechsig and Gowers) occupy the most external position on the lateral sur- 
 face, and other cord continuations (medial fillets) the most external mesial 
 positions. Later, however (fifth month), there is added ventral to the fillets 
 the descending cortico-spinal fibers (pyramids). Their decussation takes 
 place at the cervical flexure. 
 
 By the external accessions from the alar plate above described, forming 
 terminal nuclei of overlapping tracts from above (especially the nucleus of 
 the spinal V), the tractus solitarius becomes buried, as it were, hence its deep 
 position in the adult. The great development of the reticular formation 
 may contribute to this result. As the trigeminus is the most cephalic rhombic 
 
522 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 segment, its descending fibers are not overlapped by fibers from above and 
 therefore occupy the most external position of all these descending peripheral 
 systems. 
 
 Mantle layer Inner layer Gray ret. form 
 
 \ ^JiiiiiiifK / 
 
 '^^fe^^^fe-/^^^ 
 
 53^*ri^*eLr i s* _ . -S^S^iSjajj;-.- ' : .X X; ' x -^''^ 
 
 ^^ ~:r ^5CV^^^ 
 
 F.r.a. 
 
 Restiform furrow 
 
 Rhombic lip migration | 
 
 Ext. arc. fib. in marg. layer N. XII F.r.a.v. Septum medullas 
 
 FIG. 454. Half of a transverse section through the medulla of a 13.6 mm. human embryo 
 
 (beginning of sixth week). His. 
 
 F. r. a., Beginning of white reticular formation in dorsal part of septal marginal layer. 
 Another bundle has formed more ventrally (F. r. a. v.) . 
 
 Inner layer 
 
 Roof plate 
 
 Tractus solitarius 
 
 Formatio reticularis 
 grisea 
 
 Formatio reticularis alba 
 
 N. XII Septum 
 
 medullse 
 
 Spinal V 
 
 Neuroblasts from alar plate 
 Marginal layer 
 
 Neuroblasts from alar plate 
 (Rudiment of accessory olive) 
 
 FIG. 455. Transverse section through the medulla of an 8 weeks' human embryo. His. 
 
 The terminal nuclei belonging to the auditory (acustico-facialis-abducens) 
 segment are those of the vestibular and cochlear portions of the VIII nerve. 
 
THE NERVOUS SYSTEM. 523 
 
 The development of these nuclei is not fully known, but they are derived from 
 the alar plate, except possibly Deiters' nucleus (see p. 517), the nuclei of the 
 later formed cochlear nerve occupying the more external position. The ves- 
 tibular nuclei apparently send axones both to cerebellum and reticular formation. 
 The cerebellum itself may be regarded as primitively a receptive vestibular 
 structure (p. 466) and probably receives vestibular root fibers. The axones 
 of the cochlear nuclei pass across the median line, along the ventral border of 
 the reticular formation (second half of second month), forming the trapezium. 
 On the lateral boundary of the opposite reticular formation they ascend, form- 
 ing the lateral fillet, to the suprasegmental posterior corpus quadrigeminum. 
 Accessions are received from the superior olive, in which some of the trapezium 
 fibers terminate. 
 
 The alar plate of this segment also forms the substantia gelatinosa and the 
 anterior portions of the olivary nuclei in this region. The various remaining 
 tracts assume the same positions as further caudally. 
 
 Later, the pyramids are added ventrally to the fillet, and the great develop- 
 ment of the pons leads to its covering the ventral surface of part of this region. 
 Owing to the late development of the pons and pyramids, the trapezium is thus 
 uncovered and lies on the ventral surface of the rhombic brain during the third 
 month. It is permanently uncovered in the dog and cat. 
 
 In the trigeminus segment, the terminal nucleus of the afferent portion of 
 this nerve is probably similarly formed from the alar plate. Its axones decus- 
 sate, probably joining the fillet, and proceed to the thalamus, which is connected 
 with the pallium. Descending axones from cells in the mid-brain roof form 
 part of the trigeminus known as its descending or mesencephalic root. The 
 view has been advanced (Meyer, Johnston) that these are afferent neurones 
 equivalent to certain dorsal horn cells found in some adult and embryonic 
 Vertebrates and representing spinal ganglion cells which have become included 
 in the neural tube instead of becoming detached with the rest of the neural crest 
 (compare p. 452). 
 
 In front of the lateral recess another extensive development of the alar plate 
 occurs, evidenced by the large rhombic lip of this region. The neuroblasts 
 thus differentiated form the enormously developed pontile nuclei whose axones 
 pass across the median line (fifth month) to the opposite cerebellar hemisphere, 
 forming the middle cerebellar peduncle or brachium pontis. The pons extends 
 over the ventral surface of the cephalic part of the medulla and over the ventral 
 surface of part of the mid-brain. It receives fibres from various parts of the 
 neopallium, which form a great part of the pes pedunculi or crusta. A still 
 greater development of the alar plate forms the cerebellum. 
 
 In the mid-brain region, the reticular formation already described (p. 517) 
 is enveloped ventrally and laterally by the upward extension of the medial and 
 
524 TEXT-BOOK OF EMBRYOLOGY. 
 
 lateral fillets, the whole comprising the tegmentum. Ventral to this are added 
 later the pons and the descending cortico-pontile, cortico-bulbar and cortico- 
 spinal bundles forming here the pes pedunculi or crusta (probably during the 
 fifth month). 
 
 The alar plate of the mid-brain region forms the corpora quadrigemina 
 (mid-brain roof). 
 
 The further changes in the gross morphology of the medulla are due mainly 
 to further growth of structures already present. The nuclei of the dorsal col- 
 umns by their increase cause the swellings on the surface of the medulla known 
 as the clava and cuneus, and likewise by their increase in size cause a secondary 
 dorsal closing in of the caudal apex of the fourth ventricle which formerly 
 extended to the cervical flexure. The tuber culum of Rolando is produced by the 
 growth of the terminal nucleus of the spinal V, and the restiform body largely 
 by the development of the afferent cerebellar fibers (Fig. 457). 
 
 The growth of the olivary nuclei produces the swellings known as the 
 olives. The above mentioned accession of the descending cerebrospinal tracts 
 to the ventral surface is indicated by the pyramids. 
 
 In the floor of the ventricle there is a longitudinal ridge each side of the 
 median line occupied by swellings produced by the nucleus of the XII and, 
 further forward, the nucleus of the VI, together with other nuclei (intercalatus, 
 funiculus teres and incertus, Streeter) which are not well understood. The 
 furrow forming the lateral boundary of this area is usually taken to be the 
 representative of the sulcus limitans and consequently the area in question 
 would be the basal plate. Lateral to it is a triangular area with depressed 
 edges the ala cinerea. It represents a region where portions of the vago- 
 glossopharyngeal nuclei (dorsal efferent and terminal nuclei of fasciculus 
 solitarius) lie near the surface. Possibly a secondary invasion by surrounding 
 more recently differentiated nuclei may account for their apparent partial 
 retreat from the surface. It is possible that the ala cinerea may be regarded 
 not so much as a part of the alar plate, but that it or rather the branchial 
 nuclei involved in its formation represents an independent intermediate region 
 corresponding to the intermediate region in the cord (J. T. Wilson). The 
 remaining portion of the alar plate, in the floor, is apparently represented 
 principally by the acoustic, especially the vestibular, field. 
 
 In the development of the segmental brain there are thus the following 
 overlapping stages: (i) The differentiation of the inner, mantle and marginal 
 layers. (2) The prima^v neural apparatus, consisting of (a) the peripheral 
 segmental neurones, the central processes of the afferent neurones entering the 
 alar or receptive plate, the efferent neurone bodies forming two main series 
 of nuclei in the basal plate, and (b) intersegmental neurones composing the 
 reticular formation in which the long tracts occupy external positions. (3) 
 
THE NERVOUS SYSTEM. 
 
 525 
 
 The further differentiation, from the alar plate, of terminal nuclei for the 
 afferent peripheral segmental neurones, the axones of the terminal nuclei 
 forming afferent tracts to suprasegmental structures. These tracts and other 
 later forming afferent suprasegmental tracts with their nuclei are laid down 
 ext( rnal to the reticular formation. (4) Formation of efferent (chiefly th ala- 
 mic(?) mid-brain and cerebellar) suprasegmental tracts which act upon the 
 intersegmental neurones or reticular formation. (5) Accession at a late s';age 
 of d svelopment of a descending system of fibres from the neopallium. T.'iese 
 lie 's entral to the preceding structures. 
 
 The Cerebellum. 
 
 It has already been pointed out that at an early period (three weeks) the 
 anterior boundaries of the thin expanded roof plate of the rhombic brain form 
 two lines converging anteriorly to the median line where 
 the roof plate is represented by the usual narrow portion 
 connecting the two alar plates (Fig. 456). It has also 
 been pointed out that the pontine flexure produces on the 
 dorsal surface a deep transverse fold in this thin roof, into 
 which vascular tissue grows later forming the chorioid 
 plexus (Fig. 448) . At this stage, the continuations of the 
 alar plates of the medulla form two transverse bands 
 which, when viewed laterally, are vertical to the general 
 longitudinal axis of this part of the brain (Fig. 448) . At 
 the same time, the rhombic lips are formed along the 
 caudal border of these bands and the latter become 
 thickened into the two rudiments of the cerebellum, a 
 considerable portion of which may be derived from the 
 lips. These rudiments are thus two transverse and 
 vertical swellings and are connected across the median 
 line by the roof plate. The attachment (taenia) of the 
 alar plate of this region to the roof plate of the fourth 
 ventricle is at first along its caudal edge. Later, by the 
 folding back and fusion of this border to form the rhom- 
 bic lips, the attachment is carried forward. Still later, 
 by the growth of the cerebellar rudiment, it is rolled 
 backward and under, as described below. The rudi- 
 ments subsequently fuse across the median line, thus 
 forming externally a single transverse structure, but internally a paired dorsal 
 median projection of the lumen marks the location of the uniting roof plate 
 (comp. Fig. 458). 
 
 FIG. 456. Dorsal view 
 of that part of the 
 brain caudal to the 
 cephalic flexure 
 (human embryo of 3d 
 week, 2.15 mm.). Hh. 
 Cerebellum; J, isth- 
 mus; M, mid-brain; 
 Rf, A7z, medulla. 
 Compare with Fig. 
 416. His. 
 
526 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 While the structure thus formed expands enormously in a lateral direction, 
 in its subsequent development its greatest growth is in a longitudinal direction. 
 The effect of this is that the continuations of the cerebellum forward (velum 
 medullare anterius} and backward (velum medullare posterius) into the adjoining, 
 brain walls of the isthmus and medulla are comparatively fixed points and are 
 completely overlapped by the spreading cerebellum, producing an appearance 
 in sagittal section as though they were rolled in under the latter structure (comp. 
 Fig. 408, F) . Another result of this longitudinal growth is the formation of fis- 
 sures running across the organ, transversely to the longitudinal brain axis. 
 First, lateral incisures separate two caudal lateral portions, the flocculi (Fig. 
 457), the median continuation of which, the nodule, is finally rolled in on 
 the under side of the cerebellum as explained above. Another transverse fissure, 
 the primary fissure, beginning in the median part and extending laterally, sepa- 
 
 ^^^^ Cerebellar hemisphere 
 
 Tasnia 
 
 Tuberculum cuneatum 
 Cla- 
 
 Tuberculum cinereum (Rolando) 
 
 Fasciculus gracilis (Goll) 
 
 Fasciculus cuneatus (Burdach) 
 
 FIG. 457. Dorsal view of the cerebellum and medulla of a 5 months' human foetus. Kollmann. 
 
 rates an anterior lobe from a middle lobe, the former comprising the future lin- 
 gula, centralis and culmen and their lateral extensions. The anterior portion 
 is rolled forward under the anterior part of the cerebellum. Another trans- 
 verse fissure next appears in the median part (secondary fissure) which later ex- 
 tends (peritonsillar) to the floccular incisure, and thereby completes the de- 
 marcation of a posterior lobe, including not only the flocculus and nodule, but 
 also the tonsilla and uvula, which are also rolled backward and under. The 
 result of this transverse fissuration would be the production of a cerebellum 
 resembling that of certain forms below Mammals where the cerebellum is well 
 developed (Selachians, Birds). A complicating factor, however, is the great 
 growth of certain lateral portions of the middle lobe, forming the future cere- 
 bellar hemispheres (Fig. 457), which causes also a lateral overlapping and rolling 
 inward of adjoining parts. This growth is the chief factor in the division 
 of the cerebellum into vermis and hemispheres and is correlated with the devel- 
 opment of the neopallium (p. 466 and Fig. 409). 
 
THE NERVOUS SYSTEM. 
 
 527 
 
 The early histological development of the cerebellum has been most closely 
 studied in Bony Fishes (Schaper) and there is every reason to suppose that 
 the processes taking place in the human cerebellum are essentially the same. In 
 that part of the alar plate forming the rudiment above described, the cells pro- 
 liferate, forming first a nuclear layer with the dividing cells along its ventricular 
 surface, and a non-nucleated outer or marginal layer. Later, owing to begin- 
 ning migration and differentiation, there is formed the usual mantle layer, 
 representing a differentiation of part of the original nuclear layer and thereby 
 forming the three layers: an inner, a mantle and a marginal. The outer cells 
 of the mantle layer increase in size and differentiate into the cells of Purkinje, 
 snaller cells within forming the granular layer. The earliest stage of differ- 
 entiation of the Purkinje cells has not been accurately described, but the axones 
 
 FIG. 458. Diagram representing the differentiation and migration of the cerebellar cells in a teleost. 
 The arrows indicate the migration of cells from the borders of the cerebellar rudiment into 
 the marginal layer; these cells probably all differentiate into nerve cells. Clear circles, indif- 
 ferent cells; circles ivith dots, neuroglia cells (except in marginal layer); shaded cells, epithelial 
 cells; circles with crosses, epithelial cells in mitosis (germinal cells) ; black cells, neuroblasts; L 
 lateral recess; A/, median furrow, above which is roof plate; R, floor of 4th ventricle (IV). 
 Schaper. 
 
 of the neuroblasts evidently proceed (end of fifth month) toward the ventricular 
 surface instead of entering the marginal layer. In this way the fibrous layer 
 (white matter) comes to lie within instead of on the outer surface as in the cord, 
 and, to some extent, in the medulla. There is thus formed the outer gray matter 
 or cortex. The axones of the Purkinje cells form the great bulk of the centrifu- 
 gal fibers of the cerebellar cortex. The marginal layer becomes ultimately 
 the outer or molecular (plexiform) layer of the adult cerebellum. 
 
 It has been seen that in the other parts of the tube development begins in 
 the medial parts of the lateral plates and thence advances toward their dorsal 
 borders, which actively develop after the corresponding stages have ceased in 
 the medial portions. The same is true of the cerebellar rudiment. In this, 
 the edges which border on the thin roof plate, i.e., those parts adjoining the 
 lateral recesses, the main roof of the fourth ventricle and the roof plate inter- 
 posed between the two original lateral cerebellar rudiments, are the last to pro- 
 
528 
 
 TEXT-BOOK OF EMB.RYOLOGY. 
 
 liferate. The cells thus formed spread into the marginal layer of the earlier 
 developed parts and by further proliferation form a nucleated layer of consider- 
 able thickness (Fig. 458). This complication is apparently essentially similar 
 to that described above in the development of the medulla. From the cells of 
 this invasion are formed a part, at least, of the granule cells, as well as the basket 
 cells and other cells which remain in the marginal (molecular) layer. These 
 are all association cells of the cerebellum. 
 
 The cerebellum reaches its full histological development very late; after 
 birth in many Mammals. These last postnatal stages of development naturally 
 
 FIG. 459. Scheme showing the various stages of position and form in the differentiation of granule 
 cells from the outer granular layer. Cajal. 
 
 A t Layer of undifferentiated cells; B, layer of cells in horizontal bipolar stage; C, partly formed 
 molecular (plexiform) layer; D, granular layer; b, beginning differentiation of granule cells; 
 c, cells in mono polar stage; d, cells in bipolar stage; e,f, beginning of descending dendrite 
 and of unipolarization of cell; g,h, i, different stages of unipolarization or formation of single 
 process connecting with the original two processes; j, cell showing differentiating and com- 
 pleted dendrites; k, fully formed granule cell. 
 
 involve principally those cells proliferated last and which lie in the mar- 
 ginal layer. These have been studied by means of the Golgi method in 
 new-born Mammals by Cajal and others. The majority of these cells form 
 granule cells by means of a progressive migration and differentiation, as shown 
 in the accompanying Fig. 459. Each cell first develops a single horizontal 
 process, then another, thus becoming a horizontal bipolar cell. Following this, 
 the cell body migrates past the Purkinje cells into the granular layer, remaining 
 in connection with the original processes by a single process. There are thus 
 formed the axone of the granule cell with its bifurcation into two horizontal pro- 
 cesses, the parallel fibers of the molecular layer. This mode of formation is thus 
 
THE NERVOUS SYSTEM. 529 
 
 similar to the unipolarization of the cerebrospinal ganglion cell. The dendrites 
 begin to be formed during the migration, branch when the cell body reaches the 
 granular layer and there finally attain the adult form. Other undifferentiated 
 cells in the marginal layer send out horizontal processes the collaterals of which 
 envelop the Purkinje cell bodies, and form the baskets. The place vacated, so to 
 speak, by the migrating granules, is filled at the same time by the developing 
 dendrites of the Purkinje cells. These at first show no regularity of branching, 
 but subsequently differentiate into the definite branches of the adult condition, 
 at fhe same time advancing toward the periphery (Fig. 460). When they 
 
 FIG. 460. Section through cerebellar cortex of a dog a few days after birth, showing the partial 
 development of the dendrites of two cells of Purkinje. Cajal. 
 
 A, external limiting membrane; B, external (embryonic) granule layer; C, partly formed molecular 
 (plexiform) layer; D, granular layer; a, body of cell of Purkinje; b, its axone; c, and d, col- 
 laterals with terminal arborizations (e). 
 
 reach this, the migration of the granules is completed and the molecular layer 
 is definitely formed. This condition, evidenced by the disappearance of the 
 outer granular layer, is usually reached in Mammals within two months after 
 birth, but in man not until the sixth or seventh year. There are observations 
 indicating that animals possessing completely developed powers of locomotion 
 and balancing at birth have more completely differentiated cerebella at that 
 time. The axones of the Purkinje cells form many embryonic collaterals which 
 are afterward reduced in number. 
 
 Of the centripetal fibers to the cerebellum, those from the inferior olives 
 .cross the median line of the medulla about the seventh or eighth week, and 
 thence advance to the vermis, reaching their final destination during the third 
 
530 TEXT-BOOK OF EMBRYOLOGY. 
 
 month. The fibers from the pontile nuclei (middle peduncle) do not develop 
 until considerably later (end of the fourth month), the time of their reaching 
 their destination in the cerebellar hemispheres not being definitely known. 
 Many at least of the centripetal fibers do not reach their full development in 
 Mammals till birth or after. Some of these fibers (climbing fibers] form arbor- 
 izations around the inferior (axone) surface of the Purkinje cell bodies and 
 later creep upward, enveloping the upper surface instead, and finally the den- 
 dritic branches. Other centripetal fibers (mossy fibers) ramifying in the 
 granular layer are varicose fibers, at first otherwise smooth. From the vari- 
 cosities a number of branches are given off which later become abbreviated and 
 modified into the shorter processes of the adult condition. This final differ- 
 entiation occurs simultaneously with the final differentiation of the dendrites 
 of the granule cells with which they come into connection. The glia elements 
 apparently develop in a manner essentially similar to their development else- 
 where. 
 
 The development of the internal nuclei of the cerebellum has not been 
 thoroughly investigated. The nucleus dentalus is well developed at the end 
 of the sixth fcetal month. Eminences passing forward and ventrally along 
 the sides of the isthmus are the earliest indications of the superior peduncles^ 
 formed later by the axones of the cells of these nuclei. 
 
 Corpora Quadrigemina. 
 
 The mid-brain roof is an expansion of the alar plate of the mid-brain. 
 Later this differentiates into the anterior and posterior corpora quadrigemina. 
 In the former, by the usual ventricular mitoses (germinal cells), a nuclear 
 layer is formed with a non-nucleated marginal layer external to it which becomes 
 the outer or zonal layer. Still later the neuroblast or mantle layer is differen- 
 tiated, there being an unusually thick inner layer. The further development 
 has not been closely studied in man. Owing to the diminished importance 
 of the anterior corpora quadrigemina (p. 467) the neuroblasts do not differ- 
 entiate into the well marked "spread out" layers characteristic of the optic 
 lobes of many Vertebrates. This is probably due to a lack of development of 
 their association neurones. 
 
 The fibers of the optic tracts grow toward the anterior corpora quadrigemina 
 in the marginal layer forming the anterior brachia. When they reach the 
 anterior corpora quadrigemina, they leave the marginal layer and penetrate 
 the gray matter forming the most external fiber layer. The medial (and some 
 lateral) lemniscus fibers enter more deeply than the optic. Neuroblast axones 
 grow toward the ventricle, turn internally to the lemniscus fibers, cross (Mey- 
 nerfs decussatiori) , and proceed as the predorsal tracts to the segmental brain 
 and cord, lying ventral to the medial longitudinal fasciculi. 
 
THE NERVOUS SYSTEM. 531 
 
 The Diencephalon. 
 
 The stage of development of the diencephalon at four weeks has already 
 been mentioned (p. 478). (Figs. 461, 471 and 472.) In the lateral walls the 
 principal feature is the presence of a furrow, the sulcus hypothalamicus, which 
 beg ; ns ventrally as an extension of the optic recess and extends dorsally and 
 caudally toward the mid-brain. A branch of it extends to the posterior part 
 of the foramen of Monro. This is the sulcus Monroi. The sulcus hypothala- 
 micus is sometimes regarded as the representative in this region of the sulcus 
 limi tans. It is doubtful whether it has the same morphological value as the 
 latter. Such a comparison is seen a priori to be difficult when it is considered 
 that this region is in the most highly modified part of the brain tube, lacking 
 
 SM 
 
 Ma. 
 
 FIG. 461. Transverse section through the diencephalon of a 5 weeks' human embryo. Dp., Roof 
 plate; Ma., mammillary recess; P. s. hypothalamus; S.M., sulcus hypothalamicus; Th. t 
 thalamus. His. 
 
 motor peripheral apparatus, and that it is also the end region of the tube where 
 all longitudinal divisions would naturally merge. The sulcus deepens till the 
 end of the second month (Fig. 467). Later it becomes shallower, but appears 
 to persist till adult life. The region of the diencephalon ventral to the sulcus, 
 as already mentioned, is termed the pars subthalamica or hypothalamus. The 
 ventral part of the optic stalk forms a transverse groove in the floor, the pre- 
 optic recess, caudal to which is a ridge or fold, the chiasma swelling, in which the 
 fibers of the optic chiasma later appear.* Caudal to this is the recess or invagi- 
 nation of the floor, representing the postoptic recess and the beginning of the 
 infundibulum (Figs. 462 and 463) . Its extremity later becomes extended into the 
 infundibular process, the posterior part of which in the fifth week comes into 
 contact with the hypophyseal (Rathke's) pouch. This is a structure formed 
 
 * According to Johnston, the chiasma is formed in front of the optic recess which would then be 
 represented by the postoptic recess. In this case the chiasma would be regarded as falling in the 
 region of the telencephalon instead of forming the optic part of the hypothalamus (comp. Figs. 402 
 and 471). 
 
532 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 from the stomodaeal epithelium and is connected with the latter by a stalk. 
 The pouch, which is at first a flat structure, develops two horns which envelop 
 
 Ant. corp. quad. Pineal 
 (ant. colliculus) region 
 
 Anterior 
 brachium 
 
 r> 
 w 
 
 
 ^>' 
 
 Pallium 
 
 Ant 
 
 olfact. lobe 
 
 Post. 
 Optic stalk 
 Hypophyseal pouch 
 
 Mammillary Lateral Tuber 
 region geniculate cinereum 
 body 
 
 FIG. 462. Lateral view of a model of the brain of a 10.2 mm. human embryo 
 (middle of 5th week). His. 
 
 the infundibulum. The cavity of the end of the infundibular process becomes 
 nearly shut off from the rest of the infundibular cavity. The process penetrates 
 the upper part of the pouch and then bending reaches its posterior surface and 
 
 Diencephalon Thalamus Pineal region 
 
 Pallium 
 
 Foramen of Monro 
 
 Sulcus hypothal- 
 amicus 
 
 Ant. olfact. lobe 
 
 Post, olfact. lobe 
 
 Lamina terminalis 
 
 Corpus striatum 
 
 Mesencephalon 
 Tegmental swelling 
 
 Mammillary region 
 Hypothalamus 
 Tuber cinereum 
 
 Recessus Hypophyseal Recessus 
 (prae?) opticus pouch infundibuli 
 
 FIG. 463. Median view of the right half of a model of the brain of a 10.2 mm. human embryo 
 (middle of 5th week). Compare Fig. 462. His. 
 
 ends blindly. In the second half of the second month epithelial sprouts, which 
 become very vascular, begin to appear, first in the lateral parts of the pouch, 
 
THE NERVOUS SYSTEM. 533 
 
 next the brain, and then extending through the pouch and finally nearly oblit- 
 erating its cavity (third month). The shape of the organ (the hypophysis) 
 formed by the union of these two parts is subsequently changed by its relations 
 to surrounding parts. Its posterior lobe is derived from the infundibular por- 
 tiDn, its anterior lobe from the pouch. 
 
 An expansion of the floor of the brain caudal to the infundibulum has been 
 mentioned as the mammillary region. Subsequently there is formed fror.i its 
 ce phalic part another evagination, the tuber cinereum. The mammillary region 
 forms the mammillary bodies. The region caudal to the mammillary region 
 la';er receives many blood vessels, thereby becoming the posterior perforated 
 space. 
 
 At the end of the fourth week the roof plate of the diencephalon is smooth. 
 At about this time the greater part of the roof expands, forming a median 
 longitudinal ridge (Fig. 464). This ridge, which remains epithelial throughout 
 life, is broader at its anterior end where it passes between the beginning pallial 
 hemispheres. As the roof plate expands further, the anterior part is next 
 thrown into longitudinal folds. The ridge forms the epithelial lining of the 
 tela chorioidea of the third ventricle (diatela). By further growth and vas- 
 cularization of its mesodermal covering at the beginning of the third month, 
 there is formed the chorioid plexus of the third ventricle (diaplexus). Lateral 
 extensions of the tela form the chorioid plexuses of the lateral ventricles (see 
 p. 547) . In the fifth week a protrusion appears at the caudal end of the median 
 ridge which is the beginning of the epiphysis. Soon after this, the furrow which 
 forms its caudal boundary extends forward along the upper part of the sides of 
 the walls, marking off a fold which is the lateral continuation of the median 
 protrusion. From the median protrusion is later formed the pineal body y 
 while from the lateral folds are formed the pineal stalk, and in front the 
 habenula, with its contained nucleus (ganglion) habenulce, and the stria 
 medullaris. Still further caudally, the anterior part of the mid-brain forms 
 a horseshoe-shaped fold the arms of which extend forward over the dien- 
 cephalon, ventral to the pineal folds. The median part of this fold forms the 
 anterior corpora quadrigemina. From its lateral extensions are formed the 
 anterior brachia of the anterior corpora quadrigemina, the pulvinar and the 
 lateral and medial geniculate bodies, all of which (pulvinar ?) later receive optic 
 fibers. The transverse furrow which forms the boundary between the rudi- 
 ments of the pineal body and of the anterior corpora quadrigemina marks the 
 location of the future posterior commissure (Figs. 464, 465 and 466) . 
 
 The part of the roof anterior to the pineal fold, as already stated, forms the 
 tela chorioidea of the third ventricle. Certain folds appear in it, however, 
 which are more clearly indicated in later stages of embryonic development 
 than in the adult and which probably represent structures already mentioned 
 
534 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 as common to the vertebrate brain ("cushion" of the epiphysis, velum trans- 
 versum, paraphysis ?) (p. 454 and Fig. 402) . 
 
 From the above it is evident that at the close of the fifth week the rudiments 
 of the various parts of the diencephalon are already well marked. These 
 rudiments are principally indicated by foldings of the walls, there being no very 
 strongly marked differences of thickness except the early differentiation between 
 the median and lateral plates. From this time on, both general and local 
 
 Lamina terminalis 
 
 Cavity of ant. olfact. lobe 
 
 Anterior arcuate fissure 
 
 Cavity of post, olfact. lobe 
 
 Chorioid fold 
 
 Hippocampal fissure 
 
 Lateral geniculate body 
 
 Pineal region 
 
 Ant. corp. quad. (ant. colliculus) 
 (extending fprward 
 into ant. brachium) 
 
 i 
 
 Angulus praethalamicus 
 
 (a) (b) 
 (c) 
 
 Corpus striatum 
 
 Roof plate of diencephalon 
 
 FIG. 464. Dorsal view of a model of the brain of a 13.6 mm. human embryo (beginning of 6th 
 week). The dorsal part of the pallium on each side has been removed. Compare with 
 Figs. 465 and 466. His, 
 
 thickenings of the lateral walls occur. This indicates a rapid proliferation 
 of the cells, especially a differentiation of the nerve cells and consequent forma- 
 tion of masses of gray and white matter. Another factor affecting the dien- 
 cephalon is the subsequent growth backward over it of the cerebral 
 hemispheres. 
 
 During the second month, the lateral walls become thickened, forming 
 a prominence on the inner surface of each side. This reduces much of the 
 cavity of the third ventricle to a cleft and in the third or fourth month a fusion of 
 
THE NERVOUS SYSTEM. 
 
 535 
 
 a portion of these two projections takes place, forming the commissura mollis 
 or massa intermedia. The condition at this stage is shown in Fig. 467. Later 
 
 Ant. corp. quad. Diencephalon 
 
 Tegmental 
 swelling 
 
 Mammillary 
 body 
 
 Tuber 
 cinereum 
 
 Pallium 
 
 Beginning of 
 fossa Sy-vii 
 
 Ant - "I olfact. 
 PostJ lobe 
 
 Optic stalk 
 
 Infundibulum Hypophyseal pouch. 
 
 FIG. 465. Lateral view of the model of the brain of a 13.6 mm. human embryo (beginning of 6th 
 week). F, Beginning of frontal lobe; T, beginning of temporal lobe. His. 
 
 this protrusion thrusts the lateral structures above described (the pulvinar, 
 geniculate bodies and brachia) to the side, the cavity of the lateral geniculate 
 
 Eplthalamus (Corpus pinealc) 
 
 Mclathalamus (Corpora geniculata) 
 
 Thalaraus 
 
 Fissiira 
 chorioidea 
 
 Pallium . 
 
 Rhiiiencephalon 
 
 Corpus striatum' 
 Sulcus hypothalamicus , - '-'' 
 
 Hvpothalamus ' 
 Chiasma opticum 
 
 .Corpora quadrigemina 
 
 .Pedunculus cerebrt 
 
 Cerebellum 
 Fosa rhoniboidea 
 
 FiG. 466. From a model of the brain of a 13.6 mm. human embryo, right half, 
 seen from the left side. His, Spalteholz. 
 
 body being obliterated. The prominence itself extends to the tegmental swell- 
 ing (see Figs. 467-8) and there thus arises the possibility of direct connections 
 
536 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 between these two structures. There can, then, be distinguished in the dien- 
 cephalon three regions, a hypothalamic region, as already described, an epithala- 
 
 Hippocampal 
 fissure 
 
 Chorioid fissure 
 Angulus praethalamicus 
 
 Foramen of Mon 
 
 Ant. arcuate fissure 
 
 Preterminal area 
 
 Ant. olfact. lobe 
 
 Olfactory nerve 
 
 Post, olfact. lobe 
 
 Hypothalamic region 
 Mammillary region 
 
 Lamina terminalis 
 
 R.o. Hypophysis 
 
 FIG. 467. Median sagittal section of the brain of a 7^ weeks' human embryo. Aq. S., Aquaeductus 
 Sylvii; C. e., fold between mid- and interbrain; C. w., commissura mollis; C. s., corpus stri- 
 atum; H. b., tegmental swelling; R.g., geniculate recess; R.i., recessus infundibuli; R. o. t 
 recessus (prae-?) opticus; S.h. y habenular evagination; 5. M., sulcus hypothalamicus; S.p., 
 pineal evagination; T. T., thalamus. His. 
 
 mic region comprising the pineal body, ganglia habenulae and related structures, 
 and finally the thalamus proper. In the latter, the geniculate bodies already 
 
 Ttialauuis 
 
 Epithalamus (Corpus ptnealei 
 
 Metathalamus 
 (Corpora geniculaial 
 
 Corpus striati 
 
 RhinencepUalon / .' / / 
 Pars optica hypothalami ,'' /' / 
 Chiasma opticum'' ,'' 
 Hypophysis'' 
 
 Pars maraillaris hypothalarai' 
 Pons (Varo 
 
 Corpora quadi igemtna 
 
 Pedunculus cerebri 
 
 -Cerebelhmi 
 --- Fossa rhomboidea 
 
 Medulla oblongaia 
 
 FIG. 468. Brain of a human foetus in the 3d month, right half, seen from the left. His, Spalteholz. 
 
 mentioned constitute a metaihalamic portion, while the portion derived from 
 the thickened part, which is continuous anteriorly with the corpus striatum, 
 
THE NERVOUS SYSTEM. 
 
 537 
 
 differentiates various nuclei, especially those which receive the general somatic 
 sensory fibers (medial lemniscus or fillet) , and other nuclei in relation to definite 
 centers of the pallium. The thalamus is thus strongly developed, owing to its 
 containing the nuclei which receive the general sensory (ventro-lateral nuclei), 
 acoustic (medial geniculate bodies), and optic (lateral geniculate bodies) 
 sys terns of fibers and which in turn send fibers (thalamic radiations) to the palli am. 
 These thalamic nuclei do not receive fibers probably until after the middle of the 
 second month. About this time the thalamic radiations begin to be for.ned 
 from the thalamic nuclei and grow toward the corpus striatum which they rjach 
 toward the end of the second month. With the first appearance of the coi tical 
 
 TbaJatnus 
 
 Pallium 
 
 BhinencepbaloQ 
 
 Becessus opticus 
 
 Chiasma Opticnm ..' / 
 Recessus infundibuli ' / 
 Infundibulum 
 
 Pedunculus cerebri 
 
 Velum medul- 
 lare an ten us 
 
 Cerebellum 
 Yen trie nlus quart us 
 Medulla oblongata 
 
 ponstvaroii] Myelon-Y^ 
 WphalohV 
 
 FIG. 469. Adult human brain, right half, seen from the left, partly schematic. Spalteholz. 
 
 layer of the developing neopallium (see p. 542) they penetrate the corpus stria- 
 tum and pass to the cortex, forming the beginning of the internal capsule, and 
 corona radiata. It has already been pointed out (p. 467) that the great develop- 
 ment of the thalamus and its radiations is more recent phylogenetically and is 
 due to the newly acquired connections with the neopallium. 
 
 Before the development of these neopallial connections, other tracts have 
 begun to appear which represent older epithalamic and hypothalamic connec- 
 tions existing practically throughout the Vertebrates (pp. 467 and 468). Some 
 of the hypothalamic connections are the mammillo-tegmental fasciculus which 
 appears early in the second month, the ihalamomammillary fasciculus 
 (Vicq d'Azyr's bundle), which appears later, and the bundles from the rhinen- 
 cephalon (p. 505) and archipallium (columns of the fornix, middle of fourth 
 month, p. 551). In the hypothalamic region is also differentiated the corpus 
 
538 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 Luysii, connected by "fiber bundles with the corpus striatum and tegmentum. 
 Epithalamic connections are represented by bundles from anterior olfactory 
 regions (stria medullaris, seventh week) , by the commissura habenularis, and by 
 bundles to caudal regions (fasciculus retrofleocus of Meynert to the inter pedun- 
 cular ganglion, middle of second month), (pp. 467 and 505.) The posterior 
 commissure fibers are formed early in the second month in the fold between 
 mid- and inter-brain (Fig. 467). (Fig. 470). 
 
 St. 
 
 FIG. 470. Construction of the brain of a 19 mm. human embryo (7^ weeks), showing the stage of 
 development of some of the principal fiber-systems. His. 
 
 C.c., posterior commissure; F. s., tractus solitarius; F.t., fasciculus spinalis trigemini (spinal V); 
 K, nuclei of dorsa! funiculi of cord; L., medial longitudinal fasciculus; M., fasciculus retro- 
 flexus of Meynert; Ma., mammillary bundle; .*"., nervus intermedius; O., olive; Ol., olfactory 
 nerve; S., fillet; St., stria medullaris thalami; T., lhalamic radiation; T. o., tractus opticus; 
 V, Gasserian ganglion; VII, facial nerve and geniculate ganglion; VIII, ganglia of acoustic 
 nerve; IX, N. glossopharyngeus; X, N. vagus. 
 
 The Telencephalon (Rhinencephalon, Corpora Striata and Pallium). 
 
 To understand the development of this part of the brain it is necessary to 
 keep firmly in mind certain relations which are laid down at a comparatively 
 early stage. Some of these relations are shown in the diagram of the inner sur- 
 face of a model of a brain of four weeks. At this stage the pallium is unpaired, 
 i.e., there is no median furrow separating the two halves of the pallial expansion. 
 The various boundaries of the pallium in one side are (i) the median line uniting 
 
THE NERVOUS SYSTEM. 
 
 539 
 
 the two halves of the pallial expansion (Fig. 471, be)] (2) the boundary line or 
 line of union with the thalamus lying caudally (pallio-thalamic boundary) 
 (Fig. 471, cd}\ (3) the boundary between pallium and corpus striatum (strio- 
 pallial boundary) (Fig. 471, bd). The boundaries of the future corpus striatum 
 are (i) the median (Fig. 471, ab), (2) the strio-pallial (Fig. 471, bd), (3) the 
 strkKhalamic or peduncular (Fig. 471, de) and (4) the strio-hypothalamic (. . r ig. 
 471, ae). The internal prominence which is the rudiment of the coipus 
 striatum, has three limbs or crura, (i) a ridge proceeding forward (anterior 
 crus), which corresponds externally to the furrow (external rhinal furrow) 
 fojming the lateral boundary of the anterior olfactory lobe, (2) a middle crus 
 
 Prosencephalon 
 (Fore -brain) 
 
 Rhinencepha 
 
 Corpus striatum 
 
 Corpora quadrigemioa 
 
 Peduuculus cerebrl 
 
 Brachium conjunctive 
 
 and velum medullare 
 
 aoterius 
 
 Pars optica liypothalarai 
 Pai-s mamillaris hypothalami .. 
 Pons [Varolil 
 
 Pars ventralis - 
 Sulcus limitans- 
 
 (Lozenge- shaped 
 brain) 
 
 Cerebellum 
 
 FIG. 471. From a model of the brain of a human embryo at the end of the first month, right 
 half, seen from the left. His, Spalteholz. 
 
 corresponding to the constriction separating the two olfactory lobes, and (3) a 
 posterior crus corresponding to the posterior boundary of the posterior olfactory 
 lobe. This latter is merged with the earlier furrow separating the telencephalon 
 from the thalamus and hypothalamus (peduncular furrow). What may be 
 called the main body of the corpus striatum, from which these limbs radiate, 
 soon becomes expressed externally by a shallow depression in the lateral sur- 
 face of the hemispheres immediately dorsal to the olfactory lobes. This 
 depression is the first indication of the /0ssa Sylvii (Fig. 465) . 
 
 The boundaries of the pallial hemisphere above indicated are identical 
 with the boundaries of the future /0r#wW 0/M<wr0. 
 
 The median lamina uniting the two halves of the pallium and the two corpora 
 striata may be termed the lamina terminates and represents the roof plate and 
 floor plate of this region. The point of meeting of the roof plate and floor 
 
540 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 plate at the end of the tube is often taken to be at the recessus neuroporicus ; 
 and the lamina terminalis or end wall of the neural tube, more strictly speaking, 
 is limited to the median wall ventral to this point. Here it will be understood 
 as including the median wall to the point where the pallio-thalamic boundary 
 begins, marked later by the angulus prczthalamicus of His (see p. 547 and Fig. 
 480). 
 
 Rhinencephalon. The term rhinencephalon is a convenient one for 
 those basal structures of the fore-brain which are in most intimate connection 
 with the olfactory nerve. The term has been extended by some to include 
 the pallial olfactory structures. For descriptive purposes it is here used in 
 the more limited sense. 
 
 At the fourth week, as already indicated (p. 546, Fig. 472) , there is a slight longi- 
 tudinal furrow on the external surface, marking the ventral limit of the pallial 
 
 FIG. 472. Lateral view of outside of brain shown in Fig. 471. His. 
 
 eminence. The part of the brain ventral to this furrow is the rhinencephalon, 
 Somewhat later the latter becomes better marked off, the fissure forming its 
 boundary on the lateral surface being the external rhinal fissure (Fig. 462). 
 Later the mesial side is also marked off by an extension of the fissure around 
 on the mesial side (medial rhinal fissure) and also by a notch, the incisura 
 prima, a continuation of which later ascends along the middle part of the 
 median surface of the hemispheres and is known as the anterior arcuate fissure 
 (fissura prima of His) . (Fig. 480.) The existence of a fissura prima in early 
 stages, however, is doubtful. At about this time, the rhinencephalon shows a 
 beginning division into anterior and posterior portions, the anterior and posterior 
 olfactory lobes, the whole structure assuming a bean-shape (comp. p. 542) 
 (Fig. 465). On the lateral surface immediately above this constriction is the 
 beginning concavity in the lateral surface of the hemispheres which marks the 
 
THE NERVOUS SYSTEM. 
 
 541 
 
 earliest appearance of the fossa Sylvii. The external rhinal fissure, as it 
 becomes more pronounced, may be regarded as an extension forward of the 
 fossa (anterior crus of the corpus striatum) . On the mesial surface the incisura 
 prima marks this constriction. With the further curvature of the hemispheres, 
 ttn anterior lobe becomes bent back under the posterior (third month), but 
 lat?r is again directed forward. It contains a diverticulum of the fore-brain 
 cavity. The cavity of the posterior lobe is not so well marked off anl is 
 bounded by the corpus striatum and the inward projection of the incii.ura 
 prima. (Figs. 462, 463, 465, 466 and 480.) 
 
 The olfactory nerve at the end of five weeks has reached the anterior lobe 
 on its ventral and posterior side. The lobe develops into the receptive center 5 for 
 the nerve the olfactory bulb; into the stalk in which the secondary olfactory 
 
 Gyms olfact. medialis 
 Gyrus olfact. medius 
 
 Gyrus diagonalis -i 
 
 Cerebellum 
 
 Gyrus ambiens 
 Gyrus semilunaris 
 
 Olive 
 
 FIG. 473. Ventral view of the brain of human foetus at the beginning of the 4th month. Kollmann. 
 
 tract proceeds ; and also into a triangular area where the tract divides the 
 trigonum. The posterior olfactory lobe develops into the anterior perforated 
 space and an eminence known as the lobus pyriformis which becomes reduced 
 later (comp. Fig. 408, G and H). From it is developed the gyms olfactorius later- 
 alis, connected with the lateral division of the olfactory tract and thegyri ambiens 
 and semilunaris (Fig. 473). On the mesial wall, the posterior lobe is especially 
 connected with the region between the anterior arcuate fissure and the lamina 
 terminalis (trapezoid area of His, parolfactory or preterminal area of G. Elliot 
 Smith) (Fig. 480) . Part of this mesial region represents the anterior portion 
 of the archipallium (comp. Fig. 408, G and H and p. 512). 
 
 Corpora Striata and Pallium. The leading feature of the development 
 of this part of the brain is the great expansion of the pallial hemispheres. That 
 part of the brain wall marked externally by the fossa Sylvii and internally by the 
 body of the corpus striatum, and especially that part where the corpus striatum 
 
542 TEXT-BOOK OF EMBRYOLOGY. 
 
 is continuous with the thalamus (peduncular part) , may be considered as a fixed 
 point from which the pallial walls expand in all directions, anteriorly, dorsally 
 and posteriorly, i.e., in both transverse and longitudinal directions. At first, 
 this expansion causes the pallial hemispheres to assume a bean-shape with the 
 hilum at the fixed point (Fig. 465). The anterior end curves downward and 
 forms the frontal lobe with its enclosed cavity (anterior horn of the lateral ven- 
 tricle). The posterior end curves downward caudally and forms the temporal 
 lobe with the descending horn of the lateral ventricle. At the same time, owing 
 to the great expansion in a transverse plane of each pallial eminence, the 
 median lamina uniting them (Figs. 463 and 464) not sharing in this growth, 
 there are formed the hemispheres with their cavities, the lateral ventricles, and 
 the great longitudinal fissure between the hemispheres. Later, vascular 
 mesodermal tissue fills this fissure, forming the faloc cerebri. The paired 
 cavities of the pallium are connected with the unpaired end-brain cavity (aula) 
 by the foramina of Monro, the boundaries of which are the same as those of the 
 pallium described above (p. 538). 
 
 At first the walls of the telencephalon, like those of other parts of the tube, 
 are epithelial in character and nearly uniform in thickness. By proliferation 
 there is formed a several-layered epithelium differentiated into an inner 
 nuclear layer and an outer marginal layer. Later a mantle layer is differen- 
 tiated. The hemispheres are late in development and until the end of the 
 second month the walls are thin and simply show the above three layers. 
 Toward the end of the first month a greater activity in cell proliferation takes 
 place in the basal portion of the telencephalon which thickens into the corpus 
 striatum. At eight weeks there first appears on the external surface of the 
 corpus striatum, a cortical layer of cells lying next the marginal layer and sepa- 
 rated from the inner layer by an intermediate layer comparatively free of cells 
 and known as the fibrous or medullary layer (see p. 554) . The differentiation 
 thus begun extends gradually around the circumference of the hemispheres 
 until the mesial surface is reached. This differentiation permanently ceases 
 at the medial pallial margin. The cortical layer does not extend as far as 
 the medullary layer, thus leaving an uncovered medullary layer on the mesial 
 hemisphere wall. As a result of this, there is in this region, passing toward 
 the median line, (i) a region covered with a cortical layer (limbus cortical is 
 of His); (2) an uncovered medullary layer (limbus medullaris); (3) a fibrous 
 transitional zone (the tcenia) passing into (4) a membranous zone, the roof 
 plate. 
 
 This process resembles that taking place in other parts of the neural tube, 
 in which there is the same progressive development from the ventral portion 
 of the lateral wall to the dorsal border of the same, where the latter passes into 
 the roof plate which is either ependymal or expanded into a thin membrane. 
 
THE NERVOUS SYSTEM. 543 
 
 The longitudinal growth of the hemispheres naturally affects the form of a 
 number of its structures. As already mentioned, this growth consists in an 
 elongation around a fixed point, which may be regarded as located on its ven- 
 tral border, the result of this being a curving down in front and behind ihis 
 point. This is especially marked in the caudal half which thereby becones 
 curled first ventrally and then forward, thus forming a spiral. This growth in 
 length is interstitial, i. e., due to expansion of the intermediate parts, and fari 
 passu with it there is an elongation not only of the corpus striatum and 
 structures in the mesial hemisphere wall (hippocampal formation, corpus ca llo- 
 sum, chorioid plexus of lateral ventricle), but also of adjacent thalamic struc- 
 tures (stria terminalis or semicircularis), as described later. 
 
 FIG. 474. View of the inside of the lateral wall of anterior part of fore-brain. Human embryo 
 
 of about 4^ weeks. His. 
 
 C, Corpus striatum; H, pallium; h. R, posterior olfactory lobe; L, lamina terminalis; O, re- 
 cessus (prae-?) opticus; R. i., recessus infundibuli; S. M.. sulcus hypothalamicus; St, hypo- 
 thalamus; T, thalamus; v. R., anterior olfactory lobe. 
 
 The early divisions of the corpus striatum have been mentioned, and also 
 the relations of its parts with the rhinencephalon. The anterior end of the 
 corpus striatum at this period and later shows a longitudinal division into 
 three portions, a lateral, a middle and a medial, due to the original division 
 into three limbs described above (p. 538). (Figs. 474, 475, and 476.) With 
 the elongation backward of the hemisphere the corpus striatum also becomes 
 elongated, being drawn out and curled around the peduncle or stalk of the 
 hemisphere and forming a thickening along the elongated wall. This caudal 
 prolongation of the striatum is its cauda (tail) and extends to the tip of the in- 
 ferior horn (Figs. 475 and 476). The medial portion of the corpus striatum 
 forms a triangular projection (Figs. 464 and 466) the edge of which is directed 
 toward the foramen of Monro. 
 
544 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 The stalk of the hemisphere has already been mentioned as including 
 that part where corpus striatum and thalamus meet. In this region, according 
 
 v.Rl. 
 
 FIG. 475. View of inside of the lateral wall of lateral ventricle of a human foetus at beginning 
 
 of third month. His. 
 
 Bb, bulbus olfactorius; C.L, lateral limb of corpus striatum; C.m., medial segment (consisting of 
 the middle and inner limbs) of the corpus striatum. The furrow between these two parts 
 opens into the anterior olfactory lobe; hRl., posterior olfactory lobe; L.f., frontal lobe; L.O., 
 occipital lobe; Og., olfactory nerve; R. i., recessus infundibuli; R. <?., recessus (prse-?) opticus; 
 St., stalk of hemisphere (strio-thalamic junction); V.I., lateral ventricle; v.Rl.+Bb, anterior 
 olfactory lobe. 
 
 to some, there is a. fusion of the striatum, the medial wall of the hemisphere and 
 the anterior part of the thalamus. According to others, the increase in bulk of 
 
 Medial wall 
 
 Chorioid plexus of 
 lateral ventricle 
 
 Lamina terminalis 
 
 Taenia thalami 
 Thalamus 
 
 Habenula 
 Trigonum subpineale 
 Cerebellum 
 
 Myelencephalon 
 
 Lateral ventricle 
 :audate nucleus (head) 
 
 Medial wall 
 Caudate nucleus (tail) 
 Pineal body 
 Median sulcus 
 
 Mesencephalon 
 Fourth ventricle 
 
 FIG. 476. Dorsal view of the brain of a 3 months' (45 mm.) human foetus. The dorsal part of each 
 cerebral hemisphere has been removed. Kollmann. 
 
 this region is produced by a simple thickening of the walls, thus causing a flat- 
 tening out or shallowing of the grooves marking the junctions of striatum and 
 
THE NERVOUS SYSTEM. 
 
 545 
 
 FIG. 477. i, 2 and 3, Schematic horizontal sections through human embryonic fore-brains at dif- 
 ferent stages of development; 4, vertical section through fore-brain at about same stage as i. 
 Goldstein. 
 
 a, That part of the lateral ventricle lying between the corpus striatum and the junction of medial 
 hemisphere wall and thalamus (leading into the inferior horn); b, furrow or trough between 
 mesial hemisphere wall and thalamus, produced by backward extension of hemisphere; c. i., 
 internal capsule; P.M., foramen of Monro; h, external surface at junction of mesial hemi- 
 sphere wall and thalamus; Str., corpus striatum; Th., thalamus; U, place where mesial hemi- 
 sphere wall continues into the thalamus wall (junction of hemisphere wall and thalamus); 
 U 1 , place where mesial hemisphere wall is continuous with lateral hemisphere wall. 
 
 In i, owing to the thickening of U and growth of the corpus striatum, these two are brought 
 into apposition, as indicated by the dotted lines on the right, and apparently fuse, obliterating 
 a and producing the condition shown in 2 and 3. In 2 and 3 the position of the former 
 space a is indicated by the dotted lines a a' By comparison with 4, it will be seen that this 
 obliteration by apparent fusion is actually produced by a filling up from the bottom of a (in- 
 dicated faintly by dotted lines on the right in 4). The thickening of the walls at this region 
 also produces a shallowing of b (indicated by dotted lines on the right in i). The principal 
 cause of this general thickening is the passage of the fibers of the thalamic radiation to the 
 hemispheres and, later, of fibers from hemisphere to pes, forming the internal capsule (4, 2 
 and 3). 
 
546 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 thalamus on the ventricular surface, and between medial hemisphere wall and 
 thalamus externally (Fig. 477). The effect is much the same whether accom 
 plished by apposition and fusion or by interstitial thickening, massive con- 
 nections being formed which consist mainly of fibers connecting hemispheres 
 and thalamus, the foramen of Monro at the same time being changed in form 
 to a slit. From the metathalamic region the fibers of the optic and acoustic 
 pathways grow forward into the hemispheres (see also p. 537), entering more 
 caudally and forming the retro- and sublenticular portions of the internal capsule 
 (comp. p. 537). That part of the thalamic radiation from the anterior portion 
 of the thalamus (fillet pathway) also forms a part of the internal capsule as 
 described on p. 537. Later, the internal capsule is completed by the growth 
 
 Medial wall 
 
 Caudate nucleus 
 
 Internal capsule 
 
 Lentiform nucleus 
 
 Lateral wall 
 
 Chiasma 
 Recessus infundibuli 
 
 Chorioid fissure 
 Mesencephalon 
 
 Pedunculus cerebri 
 
 Cerebellum 
 
 Myelencephalon 
 
 FIG. 478. Lateral view of the brain of a 3 months' (42 mm.) human foetus. The lateral wall of 
 the left cerebral hemisphere has been removed. His, Kollmann. 
 
 from the pallium of descending fibers from the neopallial cortex, through 
 the striatum to the pes. By these various traversing fibers the striatum is 
 divided into the nucleus lenticularis or lentiformis and the nucleus caudatus. 
 The posterior arm of the internal capsule is formed by fibers passing between 
 and thus separating thalamus and lenticularis (Figs. 477 and 478). 
 
 THE ARCHIPALLIUM. 
 
 During the fifth week, following the stage shown in Figs. 471 and 472, 
 the pallial evaginations or hemispheres have become much more pronounced 
 and consequently the foramina of Monro much better defined. A comparison 
 will show that the boundaries of the foramen of Monro are essentially unaltered. 
 Anteriorly it is bounded by the medial wall connecting the two hemispheres, 
 posteriorly by the boundary between pallium and thalamus, ventrally by the 
 corpus striatum and junction of it and thalamus (Figs. 463 and 479). 
 
THE NERVOUS SYSTEM. 
 
 547 
 
 At the beginning of the sixth week the foramen of Monro has changed some- 
 what in shape. The pallio-thalamic part of its boundary passes forward and 
 forms the above-mentioned (p. 540) acute angle (angulus praethalamicus) with 
 that part of the wall uniting the two hemispheres (lamina terminalis). The 
 latter wall descends to the region of the optic recess. The inferior part of the 
 foramen is partly closed by the medial part of the corpus striatum as already 
 described. (Comp. Figs. 479, 464 and 466.) In the ependymal mesial wall 
 of the hemispheres just below the taenia, described above, there arises a folding 
 inward, which begins anteriorly near the angulus praethalamicus and proceeds 
 caudally along the upper (pallio-thalamic) border of the foramen of Monro. 
 This infolding is the chorioid fissure. In the ependymal mesial wall there are 
 
 Pallium 
 
 Foramen of Monro 
 Corpus striatum 
 
 Eye 
 
 III ventricle 
 Chorioid fissure 
 
 Mesodermal tissue, 
 forming later the 
 chorioid plexus. 
 
 FIG. 479. Transverse section through fore-brain of a i6mm. embryo (six to seven weeks). His* 
 
 now the following : limbus chorioideus (the infolded part) and a small strip of the 
 ependyma wall below the fold, the lamina infrachorioidea (Fig. 480). This 
 imagination soon becomes very deep, resulting in the formation of a double- 
 layered ependymal fold (the chorioid fold, plica chorioidea) lying in the lateral 
 ventricle over the corpus striatum (Figs. 479, 464 and 482). Later, vascular 
 mesodermal tissue passes in from the falx between the lips of this fold and 
 thereby forms the chorioid plexus of the lateral ventricles. The chorioid fissure 
 is at first quite short, but becomes elongated (Fig. 481) with the above-described 
 posterior elongation of the hemisphere of which it is a part, and thus extends 
 into the inferior horn of the temporal lobe. (Figs. 481 and 482.) 
 
 Toward the end of the second month, according to some authorities (His), 
 but not until considerably later, according to others (Hochstetter, Goldstein), 
 another furrow appears in the limbus corticalis above and parallel to the chori- 
 
548 TEXT-BOOK OF EMBRYOLOGY. 
 
 oid fissure, and known as the posterior arcuate fissure. This fissure does not 
 extend at first as far forward as the chorioid, but extends farther caudally, 
 arching downward in the temporal lobe around the caudal end of the chorioid 
 fissure (Fig. 481). The posterior arcuate fissure is a total fissure, involving the 
 whole wall and producing a fold on the inner surface of the medial hemisphere 
 wall (plica arcuata). The temporal or caudal part of this whole formation 
 persists in the adult without much further change. The fissure here becomes 
 the hippocampal fissure separating the fascia dentata from the gyrus hippocam- 
 pus; the part rolled in by the hippocampal fissure produces the eminence in 
 the lateral ventricle known as the cornu ammonis or hippocampus major; 
 
 FVW-* 
 
 Vmr Fstr hRh 
 
 FIG. 480. Diagram of a graphic reconstruction of the mesial hemisphere wall of a 16 mm. human 
 embryo (about six weeks). His, Ziehen. Cavities are dotted, cut surfaces are lined. 
 
 Apt, Angulus praethalamicus; Atr, preterminal area; Fpr, anterior arcuate fissure (fissura prima); 
 Frhl, mesial termination of lateral rhinal fissure; hRh, posterior olfactory lobe (tuberculum 
 olfactorium + substantia perforata anterior); Lt, lamina terminal's (lined); Vmr, depression 
 between the two olfactory lobes; vRh, anterior olfactory lobe (bulbus olfactorius + tractus 
 olfactorius + trigonum olfactorium). 
 
 the edge of the limbus corticalis forms the fascia dentata; the limbus medullaris 
 or exposed fibrous part is thefimbria which is continued by its thinning edge 
 or tania fimbricB into the ependymal or epithelial portion (lamina chorioidea) 
 of the chorioid plexus of the lateral ventricle. The chorioid plexus is attached 
 by the taenia chorioidea and lamina infrachorioidea (here the lamina affixa) to 
 the brain wall, usually near the junction of corpus striatum and thalamus, 
 thereby forming a part of the wall of the inferior horn of the lateral ventricle. 
 At this line of junction of thalamus and hemisphere wall is formed the stria 
 terminalis. The fimbria is continuous anteriorly with the posterior pillar of 
 the fornix. (Fig. 482.) 
 
 The anterior part of the hippocampal formation above described undergoes 
 
THE NERVOUS SYSTEM. 
 
 Corpus callosum Hippocampal fissure 
 
 549 
 
 Olfactory stalk 
 
 . 
 
 Lamina terminalis | 
 Anterior commissure 
 Beginning anterior column of fornix 
 
 Hippocampal fissure 
 horioid fissure 
 
 FIG. 481. Graphic reconstruction of the mesial hemisphere wall of a human foetus 
 
 (fourth month). His, from Quain's Anatomy. 
 
 C and v, Anterior and posterior parts of preterminal area; li, lamina infrachorioidea; km, limbus or 
 border of mesial hemisphere wall (gyrus dentatus and fimbria) between hippocampal and 
 chorioid fissures; P, "stalk" of hemisphere. 
 
 falx 
 
 FIG. 482. Diagram of a transverse section through the fore-brain of a human foetus (fourth 
 month) to show the relations of the margins of the mesial walls of the hemispheres. His, 
 from Quain's Anatomy. 
 
 Cs., corpus striatum; fi. t limbus medullaris (fimbria); fa., limbus corticalis (gyrus dentatus); h.f. t 
 hippocampal fissure; Th. } thalamus 
 
550 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 further modifications, due principally to the development of commissural fibers 
 in this region. Some of these commissural fibers connect the representatives 
 on each side of the hippocampus (limbus corticalis) of this region, forming the 
 fornix commissure, but most of them (corpus callosum) connect the rest of the 
 cortical areas (neopallial areas) of the two hemispheres. 
 
 There are two views regarding the formation of these commissures. Ac- 
 cording to one view, the first commissural fibers appear in the upper (dorsal) 
 part of the lamina terminalis. The latter subsequently expands pari passu 
 
 Corpus callosum 
 Fornix (continuation of fimbria) J 
 
 Callosal (continuation of hippocampal) fissure 
 
 i 
 
 Olfactory stalk | \ j 
 
 Optic commissure (chiasma) N^fe-fe.-. 
 
 Lamina terminalis | 
 Anterior commissure 
 
 Uncus 
 
 Hippocampal fissure 
 
 FIG. 483. Graphic reconstruction of the mesial hemisphere wall of a 120 mm. foetus (end of four 
 
 months). His, from Quain's Anatomy. 
 6, Fimbria; cs , cavity of septum pellucidum ("fifth" ventricle, ventricle of Verga); km, limbus 
 
 corticalis (gyrus dentatus); P, stalk of hemisphere; v, outline of cavity of hemisphere (lateral 
 
 ventricle) . 
 
 with the expansion of the corpus callosum. The commissural fibers are thus 
 confined to the original walls connecting the two hemispheres. According to 
 the other view, there is a secondary fusion of the mesial hemisphere walls and 
 in these fusions the fibers cross. The first fibers appear during the third month 
 and form at first a small band in the upper part of the lamina terminalis (Fig. 
 481). These fibers come partly from the limbus corticalis (fornix commissural 
 fibers) and partly from other parts of the cortex (callosal fibers), in either case 
 traveling along the intermediate layer. According to the fusion view, the 
 exposed intermediate layers (limbi medullares) fuse where the fibers cross. 
 This fusion can easily be imagined by conceiving the opposite surfaces in 
 
THE NERVOUS SYSTEM. 
 
 551 
 
 question to be brought together in the upper part of Fig. 482. It is more prob- 
 able, though, that not only the first fibers cross in the lamina terminalis, but 
 that the later ones also cross in extensions of the latter. There are three views 
 regarding the further development of the corpus callosum. The first is that 
 all parts are represented at this stage, future growth being by intussusception of 
 fibers ; the second is that the part first formed represents the genu, the rest being 
 added caudally; the third (His) is that this first formed part represents Ihe 
 middle portion of the callosum, both anterior (genu and rostrum) and posterior 
 (splmium) portions being subsequently added (Figs. 481 and 483). This 
 latter view is indicated in Fig. 483, the later additions being shaded darker. 
 
 As the callosal fibers connect the limbi medullares, the limbus corticalis 
 anl the arcuate fissure, corresponding to the gyrus dentatus and hippocan pal 
 fissure of the temporal lobe, lie dorsal to the callosum. The limbus corticalis 
 is reduced to a mere vestige (indusium griseum and strice Lancisi) on the 
 dorsal surface of the corpus callosum the fissure becoming the callosal fissure. 
 The part of the limbus medullaris ventral to the corpus callosum, corre- 
 sponding to the fimbria of the temporal lobe, forms the posterior pillars and 
 body of the fornix. 
 
 These relations are shown in the following table from His (slightly modi- 
 fied) : 
 
 Upper callosal region 
 
 Hippocampal region 
 
 
 
 Upper lip of arcuate 
 
 Gyrus cinguli 
 
 Gyrus hippocampi 
 
 
 
 fissure 
 
 
 
 
 
 Arcuate fissure 
 
 Fissura corporis cal- 
 
 Fissura hippocampi 
 
 Limbus Corticalis 
 
 
 
 losi 
 
 
 
 
 Cortical layer of low- Cortical covering of 
 
 Gvrus dentatus 
 
 
 
 er lip of arcuate callosum (indusium 
 
 
 
 
 fissure 
 
 griseum and striae 
 
 
 
 
 Lancisi) 
 
 
 Limbus Medullaris < 
 
 Medullary part of 
 lower lip 
 
 Callosum and fornix 
 
 Fimbria 
 
 Taenia 
 
 
 Taenia fornicis 
 
 Taenia fimbriae 
 
 Lamina chorioidea 
 
 
 Plica chorioidea 
 
 Plica chorioidea 
 
 Lamina infrachorio- 
 
 Lamina affixa 
 
 Taenia chorioidea 
 
 idea 
 
 Fibers from the hippocampus enter the fimbria and pass forward in the pos- 
 terior pillars and body of the fornix. In or near the lamina terminalis these 
 fibers of the fornix descend, forming the anterior pillars of the fornix, and thence 
 pass back of the anterior commissure and caudally to the mammillary region. 
 
552 TEXT-BOOK OF EMBRYOLOGY. 
 
 They are joined by fibers from the dorsal surface of the callosum (fornix 
 longus), i.e., from the vestigial hippocampal formation, many of which also 
 descend in front of the anterior commissure to the rhinencephalon. The trian- 
 gular mesial area (septum pellucidum) included between callosum and fornix 
 probably represents an extended part of the lamina terminalis or "commis- 
 sure-bed," in which a cavity is formed, the so-called fifth ventricle and ventricle 
 of Verga. A remnant of the hippocampal formation at the anterior end of 
 the callosum is represented by the gyms subcallosus (Fig. 483). 
 
 THE NEOPALLIUM. 
 
 The hippocampal or cornu ammonis formation and preterminal area 
 represent the older part of the pallium (archipallium) comp. pp. 468 and 469. 
 This part of the pallium is olfactory in character, being mainly a higher center 
 for the reception of secondary and tertiary olfactory tracts. In its extension 
 backward and partial obliteration by the corpus callosum, its embryologic 
 presents a striking similarity to its phylogenetic development (compare p. 468 ) 
 The rest of the pallial hemispheres (neopallium) are occupied by the non- 
 olfactory higher centers. 
 
 The further growth of the neopallial hemispheres leads to their extension 
 backward, overlapping the caudal portions of the brain tube. In the course 
 of this extension the occipital lobe and its cavity, the posterior horn of the lateral 
 ventricle, are formed. The growth of various portions of the hemisphere sur- 
 face is unequal, producing folds (convolutions) and fissures. This folding 
 may be partly due to growth in a confined space, but especially important is 
 the relation between gray and white matter. The gray matter, containing not 
 only fibers but also neurone bodies, remains spread out in a comparatively thin 
 layer, probably to accommodate associative connections. The white matter, on 
 the other hand, increases in thickness. This leads to a folding of the outer 
 layer. The position of these folds is probably partly determined by the local 
 histological differentiation and growth of various cortical areas (p. 557). 
 Only some of the earliest and most important of these folds will be mentioned 
 here. 
 
 It has been seen (p. 539) that early in the development of the pallium a 
 shallow depression appears on the external lateral surface of each hemisphere, 
 the fossa Sylvii (Fig. 484). The bottom of this is the future insula. It is ex- 
 ternal to the corpus striatum and does not grow as rapidly as the parts bound- 
 ing it, which consequently overlap it, forming its opercula. These bounding 
 walls are formed by the fronto-parietal lobe on its upper side, by the temporal 
 on its lower, and by the orbital on its anterior. The temporal and fronto- 
 parietal opercula begin about the end of the fifth month, the temporal at first 
 
THE NERVOUS SYSTEM. 
 
 553 
 
 growing more rapidly but later the fronto-parietal, thereby changing the 
 direction of the Sylvian fissure from an oblique to the more horizontal angle 
 characteristic of man as compared with the ape. In the meanwhile the 
 development of the frontal lobe leads to its also overlapping the insula. If the 
 
 Parietal lobe 
 
 Occipital lobe 
 
 Mesencephalon 
 Cerebellum 
 
 Frontal lobe 
 Insula 
 
 Bulbus olfactorius 
 
 Gyms olfactor. lat. 
 
 Gyrus semilunaris 
 Gyms ambiens 
 
 FIG. 484. Lateral view of the brain of a human foetus at the beginning of the 
 4th month. Kollmann. 
 
 frontal lobe fully develops, it forms a U-shaped operculum between the fronto- 
 parietal and the orbital, if it does not so fully develop it forms a V-shaped 
 operculum, and a still less developed condition is shown by a Y-shaped arrange- 
 ment in which the frontal lobe does not completely separate the fronto-parietal 
 
 Corpus callosum 
 Gyrus cinguli | 
 
 I 
 
 Sulcus corp. callosi 
 I Splenium 
 
 |, Fissura parieto-occip. 
 
 Cavum septi pellucidi 
 Lamina rostralis 
 Area parolfactoria ^ 
 (praeterminalis) 
 
 Cuneus 
 
 Fissura calcarina 
 
 N. olfact. | | Fiss. rhinica 
 N. optic. Lob. temp. 
 
 FIG. 485. Median view of the left half of the brain of a human foetus at the end 
 of the 7th month. Kollmann. 
 
 and orbital opercula. The opercula cover the fore-part of the Sylvian fossa 
 during the first year. Conditions of arrested development are thus indicated by 
 the Y-shaped anterior ascending branch of the Sylvian fissure coupled with an 
 absence of the pars triangularis and also by a partial exposure of the island 
 
554 TEXT-BOOK OF EMBRYOLOGY. 
 
 of Reil. In the ape the frontal operculum is absent and the island of Reil 
 partly exposed. 
 
 Toward the end of the third month the calcarine fissure appears, producing 
 on the ventricular surface the eminence known as the calcar avis. At the 
 beginning of the fourth month the parieto-occipital fissure unites with it forming 
 the cuneus. The parieto-occipital reaches the superior border of the hemi- 
 spheres by the sixth or seventh month. At the sixth month the fissure of Rolando 
 (central fissure) appears. The condition of the surface of the hemisphere at 
 the end of the seventh month is shown in Figs. 485 to 488. 
 
 The early histogenetic development of the pallial wall, resulting in the dif- 
 ferentiation into the usual ependymal, mantle and marginal layers, has been 
 mentioned. (Fig. 489). The next stage, already alluded to (p. 549), marks a 
 
 Gyrus front, med. ^fl| SrV 
 
 Mj* } \ ., ^B m Sulcus front, sup. 
 
 Gyrus front, inf. ^lH f v*-| 
 
 JP* I * L_^ Sulcus front, inf. 
 
 Gyrus front, sup. 4 gp*^ I . \& 
 
 4 V^iHH Sulcus praecentralis 
 
 Gyrus praecent. - "jjaUr-- * , 
 
 ^*****t^ Jf J Sulcus centralis 
 
 *--; '% s +.'-?**'' ^H_ Snlcus postcentralis 
 
 Lobulus par. sup. -fll - m 
 
 V'-v . yT~_/_ Sulcus interparietalis 
 
 Lobulus par. inf. ^H *? 
 
 V 'f^tldJft^HJIr; '''' s/ Fissura parieto-occipit. 
 Lobus occipitalis 3^^^^^ ^^^^^^ 
 
 FIG. 486. Dorsal view of the cerebral hemispheres of a human foetus at the end 
 of the yth month. Kollmann. 
 
 difference in development between the pallium, as well as other supraseg- 
 mental structures, and the rest of the walls of the neural tube. This stage 
 consists apparently in a further migration outward of the neuroblasts and their 
 accumulation under the marginal layer, forming, at eight weeks, a definite 
 layer of closely packed cells, the beginning of the cortex (Fig. 490). Later 
 neuroblast migrations probably add to this layer. It has already been men- 
 tioned that the fibers of the thalamic radiation appear in the pallial walls about 
 this time. They proceed internally to the cortical layer and thus mark the 
 beginning of the fiber layer (medullary layer) which by later myelination 
 becomes the white matter of the hemispheres. 
 
 The extension of the process of differentiation of the cortical layer from the 
 region of the corpus striatum over the rest of the pallium has also been men- 
 tioned (p. 542). It is probable that the afferent pallial fibers (thalamic radia- 
 tion) in their growth keep pace with this process. Those fibers from the lateral 
 
THE NERVOUS SYSTEM. 
 
 555 
 
 geniculate bodies proceed to the occipital region, those from the medial genicu- 
 late bodies to the temporal, and those from the ventro-lateral thalamic nuclei 
 (continuation of the medial, fillet) to the future postcentral region. The 
 afferent pallial fibers are often termed the afferent or ascending projection fibers. 
 
 Sulcus postcentralis 
 
 Sulcus centralis 
 
 Lobus parietal, sup. 
 
 Region of gyrus sup- 
 
 ramarg. and angular. 
 
 Ramus post. 
 
 Sulcus tempor. med. 
 
 Post, pole 
 of cerebrum 
 
 Sulcus front, inf. 
 
 Ramus ant. asc-. 
 Fissura Sylvii 
 
 Lobus temporalis 
 
 Gyrus temp. sup. Gyrus temp. med. 
 
 FIG. 487. Lateral view of the right cerebral hemisphere of a human fcetus at the end 
 of the yth month. Kollmann. 
 
 The axones of the neuroblasts of the cortical layer grow inward, entering the 
 medullary layer. Their peripherally directed processes become the apical 
 dendrites of the pyramid cells into which most of the cortical cells differentiate. 
 According to Mall and Paton, this change of direction in the growth of the axone 
 is due to a turning of the cell axis during its outward migration. It would seem 
 
 Sulcus orbitalis 
 
 Insula 
 Gyrus olf. lat. 
 
 Gyrus semilun. 
 
 Gyrus ambiens 
 Pyramid 
 Medulla 
 
 Sulcus olfactorius 
 Lobus olfactorius 
 
 Post, pole of cerebrum 
 
 FIG. 488. Ventral view of the brain of a human foetus at the beginning 
 of the sixth month. Retzius, Kollmann. 
 
 more probable that the cells retain an original bipolar character and that the 
 inner processes differentiate into axones instead of the cells going through a 
 monopolar stage (pp. 484 and 485 and Figs. 424 and 425). The axones of the 
 cortical cells form either efferent or descending projection fibers, proceeding to 
 
556 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 other parts of the nervous system, or crossed (callosal) and uncrossed association 
 fibers, connecting various cortical areas of the hemispheres. The basilar 
 dendritic processes of the pyramid cells and the axone collaterals develop last. 
 Many details of development of the cells in Mammals are not completed until 
 after birth (Fig. 491). 
 
 m 
 
 IrK'S 
 
 .. .t 
 
 Ml 
 
 FIG. 489. 
 
 FIG. 490 
 
 FIG. 489. Section through the pallial wall of a two months' human foetus. His, Cayal. 
 a, Layer of germinal cells; b, nuclear layer; c, mantle layer; d, marginal layer; e, germinal cell 
 
 FIG. 490. Section through the pallial wall of a human foetus at the beginning of 
 
 the third month. His, Cajal. 
 
 a, Layer containing germinal cells; b, fibrous (medullary) layer (rudimentary white matter); c, layer 
 of neuroblasts forming rudimentary cortical gray matter; d, marginal layer (future molecular 
 layer); e, germinal cell; /, g, neuroblasts with radial processes. Spongioblasts and myelo- 
 spongium are shown on the right side. 
 
 During the fourth and fifth foetal months the cortical layer shows a differen- 
 tiation into a denser outer and an inner layer. During the sixth and seventh 
 months a differentiation and grouping of the nerve cells begins which results 
 in the formation of six cortical layers (Brodmann). These are: (i) the zonal 
 
THE NERVOUS SYSTEM. 
 
 557 
 
 layer (marginal layer, molecular layer of adult), (2) the external granular layer 
 (layer of small pyramid cells of adult), (3) pyramid layer (medium and large 
 pyramid cells), (4) internal granular layer, (5) ganglionic layer (internal pyra- 
 mid cells) , (6) multiform layer (polymorphous cells) . By various local modifi- 
 cations of this six-layered cortex the differentiation of the various histological 
 areas of the adult cortex is brought about. In the calcarine region of the 
 occipital lobe, in the sixth month, the internal granular layer differentiates into 
 
 FIG. 491. Section through cortex of a mouse foetus before birth, showing later stages of 
 
 differentiation of pyramid cells. Golgi method. Cajal. 
 
 a, large pyramid cells; b, c. medium-sized and small pyramid cells; d, beginning collaterals of, e, 
 axis-cylinders or axones; /, horizontal cell of molecular layer. Basal dendrites of pyramid 
 cells are beginning to appear. 
 
 two layers between which is formed the line of Gennari which contains termi- 
 nations of the fibers from the lateral geniculate bodies, representing the visual 
 pathway. This area is the visual cortex. In the temporal (future transverse 
 gyri) and postcentral regions, areas are differentiated which mark the re- 
 ception of the terminations of the fibers of the acoustic and somaesthetic 
 (medial fillet) pathways. These areas are thus, respectively, the auditory cortex 
 and the somasthetic (general bodily sensation) cortex. (Cf. Fig. 409.) 
 
 In the precentral region, the internal granular layer becomes merged with 
 
558 TEXT-BOOK OF EMBRYOLOGY. 
 
 the adjoining layers and practically disappears, the two inner layers become 
 more or less fused and in them certain cells develop to a great size forming the 
 layer of giant pyramid cells. It is the axones of these cells, in all probability, 
 which proceed as the pyramidal tracts through the middle part of the internal 
 capsule and pes to the epichordal segmental brain and cord. The area in 
 which these cells lie is the motor cortex (cf . Fig. 409) . Descending axones de- 
 velop similarly from cells in the calcarine area, possibly here also from large 
 pyramidal cells of the fifth and sixth layers (solitary cells of Meynert), which 
 probably pass to the anterior colliculus (operating there upon reflex eye 
 mechanisms). 
 
 In the whole pallium there are thus four great projection fields, differen- 
 tiated both by their histological structure and their connections. These are (i) 
 the archipallial olfactory area with mesial ascending and descending connections ; 
 (2) the visual; (3) the acoustic; (4) the somatic. The systems of projection fibers 
 of the three neopallial fields are lateral. The visual and acoustic fields repre- 
 sent certain specialized and concentrated groups of receptors (rods and cones, 
 hair cells of organ of Corti) upon which stimuli of a certain definite nature 
 (light and sound waves), from distant objects, are focussed by means of acces- 
 sory apparatus (eye, ear). The somatic area represents receptors scattered 
 over the whole organism. In the visual and acoustic mechanisms, the efferent 
 element is small or lacking in both peripheral apparatus and cortical areas, in the 
 somatic the efferent element is large and is represented cortically by an area 
 (motor, precentral area) distinct from that of the receptive portion (somaes- 
 thetic, postcentral area). Gustatory and other visceral areas have not been 
 well determined (vicinity of archipallium ?) . 
 
 These four primary sensori-motor fields are probably the first differentiated 
 of the various pallial cortical areas. This is evidenced by the myelination 
 (comp. p. 494) which first involves the projection fibers of these areas (at or 
 soon after birth, Flechsig), the afferent projection fibers probably myelinating 
 before the efferent (Figs. 492 and 493). 
 
 The process of myelination next spreads over areas adjoining the primary 
 areas, the intermediate areas of Flechsig. Descending projection fibers from 
 these areas in the frontal, temporal and occipital lobes are probably represented 
 by the cortico-pontile systems of fibers, securing cerebellar regulation of pallial 
 reactions. The presence of other fibers connecting with thalamic nuclei 
 is probable, but knowledge of their develoDment and connections is very 
 incomplete. 
 
 The cells whose axones form descending or efferent projection fibers con- 
 stitute only a small fraction of the cortical cells. The great majority are asso- 
 ciation cells whose axones, or collaterals, pass across the median line in the 
 lamina terminalis as the callosal fibers already mentioned (p. 550) or pass 
 
THE NERVOUS SYSTEM. 
 
 559 
 
 to distant or near parts of the same hemisphere. In general, these develop later 
 than the projection neurones and the completion of their development is carried 
 to a much later period. Variations which arise in their differentiation and ar- 
 rangement probably contribute largely to the formation of various histological 
 areas which develop at different periods. These local inequalities of growth 
 probably constitute a factor in the production of the convolutions appearing 
 later than those already mentioned in connection with the primary areas. The 
 last areas to myelinate, the terminal areas of Flechsig, are poor in projection 
 fibers and are thus composed largely (entirely ?, Flechsig) of association cells. 
 It is the extent of these last developing areas which constitutes the principal 
 difference between the human cortex and that of related forms. These pallial 
 
 B 
 
 FIG. 492. Diagram of cortical areas of mesial surface of pallium as determined by the myelogenetic 
 method Flechsig, from Quain's Anatomy. For explanation see Fig. 493. 
 
 areas are those which continue to grow in human development. Myelination 
 in the cortical areas may continue for twenty years or so. It is a significant 
 fact that the last areas to develop are comparatively poor, even when completely 
 developed, in both cells and fibers (Campbell). The association neurones 
 thus probably follow the same order of development as the projection systems. 
 As their development spreads from the primary receptive areas (perceptions ?) , 
 the incoming stimuli receive a more and more extended associative " setting" 
 (psychologically, the "meaning" or "significance" of perceptions?), extensive 
 associations between the various areas being provided by the extension of their 
 development to the terminal areas (rendering possible the association of 
 symbols: mental processes?). 
 
560 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 The general biological significance of this late development of the pallium 
 and especially of its associative mechanisms has already been alluded to. 
 These "added" parts of the nervous system are the most modifiable mechan- 
 isms of the human organism; they are those mechanisms which perform its 
 newest and most highly adaptive adjustments. The other parts of the ner- 
 vous system are fixed at birth, but the cerebral hemispheres are still plastic 
 for the reception and recording of individual experience. Such experience 
 symbolized and formulated (spoken, written, etc.) is transmitted to the next 
 generation, as already pointed out (p. 470). An example of the far-reaching 
 consequences of this capacity of the pallium is the prolonged period of infancy 
 and education of man. 
 
 FIG. 493. Diagram of cortical areas of lateral surface of pallium as determined by the myelogenetic 
 
 'method. Flechsig, from Quain's Anatomy. 
 The numerals indicate, in a general way. the order of myelination. The primary areas (i-io) are 
 
 indicated by dots, the intermediate areas (11-31) by oblique lines and the terminal or final 
 
 areas (32-36) by clear spaces. 
 
 Anomalies. 
 
 Those anomalies of the nervous system involving more general develop- 
 mental anomalies (cyclopia, anencephaly, cranioschisis, spina bifida, etc.) are 
 dealt with in the chapter on Teratogenesis (XIX) . Owing to the fact that the 
 nervous system consists of parts which are more or less separated, and yet con- 
 nected and interdependent, it is in certain respects affected differently from the 
 other organs when portions of it are injured or inhibited in development. Thus 
 an injury or inhibition in development of one part of the nervous system may, 
 because of the dependence upon this part of other perhaps distant parts, affect 
 the development of the latter. Even in the adult, injury of an axone leads to the 
 
THE NERVOUS SYSTEM. 561 
 
 disappearance of that portion of the axone distal to the point of injury; it may 
 also lead to the disappearance of the entire neurone where regeneration is not 
 possible. Such an injury during development will not only cause a disappear- 
 ance of the whole neurone, but it may also lead to the disappearance of other 
 neurones forming links in the same functional pathway. Thus a develop- 
 mental defect involving the central area will not only lead to absence of the 
 pyramidal tract, but also to partial atrophy of the corresponding fillet bundles. 
 When one cerebellar hemisphere fails to develop, there results a correlated 
 defect in its centripetal and centrifugal pathways. The opposite inferior olive 
 is practically absent, as is also the central tegmental tract leading to that olive. 
 The pontile nuclei of the opposite side, the middle peduncle leading from them 
 to the affected cerebellar hemisphere, and the fibers in the pes which pass to 
 the pontile nuclei in question are likewise suppressed, and the superior 
 peduncle and red nucleus are absent or reduced. In this case it is evident that 
 the correlated atrophy affects at least two neurones in the pathways leading to 
 and from the cerebellum. This illustrates the far-reaching character of cor- 
 related developmental defects in the nervous system arising from the nature 
 of the connections between various portions of the system. 
 
 References for Further Study. 
 
 BARDEEN, C. R.: The Growth and Histogenesis of the Cerebrospinal Nerves in Mam- 
 mals. Am. Jour, of Anat., Vol. II, No. 2, 1903. 
 
 DEJERINE, J.: Anatomic des centres nerveux. Tome I, Ch. 2 and 3. 
 
 EDINGER, L.: Vorlesungen iiber den Bau der nervosen Zentralorgane. Seventh Ed. 
 
 EDINGER, L. The Relations of Comparative Anatomy to Comparative Psychology. 
 Jour. ofComp. N enrol, and Psychol., Vol. XVIII, No. 5, Nov., 1908. 
 
 FLECHSIG, P. : Einige Bemerkungen iiber die Untersuchungsmethoden der Grosshirnrinde 
 insbesondere des Menschen. Berichten der math.-phys. Klasse d. Konigl. -Sachs. Gesellsch. d, 
 Wissensch. zu Leipzig. 1904. See also Johns Hopkins Hosp. Bull., Vol. XVI, 1905, pp 
 
 45-49- 
 
 HARDESTY, L: On the Development and Nature of the Neuroglia. Am. Jour, of Anat. t 
 
 Vol. Ill, No. 3, July, 1904. 
 
 HARRISON, R. G.: Further Experiments on the Development of Peripheral Nerves. 
 Am. Jour, of Anat., Vol. V, No. 2, May, 1906. 
 
 HARRISON, R. G.: Observations on the Living Developing Nerve Fiber. Anat. Record. 
 Vol. I, No. 5, 1907. 
 
 HARRISON, R. G.: Embryonic Transplantation and Development of the Nervous 
 System. Anat. Record, Vol. II, No. 9, 1908. 
 
 HERRICK, C. J.: The Morphological Subdivision of the Brain. Jour, of Comp. Neurol. 
 and Psychol., Vol. XVIII, No. 4, 1908. 
 
 His, W.: Zur Geschichte des menschlichen Riickenmarkes und der Nervenwurzeln. 
 Abhandl. der math.-phys. Klasse der Konig. -Sachs. Gesellsch. d. Wissensch., Bd. XIII, 1887. 
 
 His, W.: Zur Geschichte des Gehirns, sowie der centralen und peripherischen Nerven- 
 bahnen beim menschlichen Embryo. Abhandl. d. math.-phys. Klasse d. Konig.-Sachs. 
 Gesellsch. d. Wissensch., Bd. XIV, 1888. 
 
562 TEXT-BOOK OF EMBRYOLOGY. 
 
 His, W.: Die Neuroblasten und deren Entstehung im embryonalen Mark. Abhandl. d. 
 math.-phys. Klasse d. Konig.-Sachs. d. Wissensch., Bd. XV, 1890. Also Arch. f. Anat. u. 
 Physiol., Anat. Abth., 1889. 
 
 His, W.: Ueber die Entwickelung des Riechlappens und des Riechganglions und iiber 
 diejenige des verlangerten Markes. Verhandl. d. Anat. Gesellsch. zu Berlin, 1889. Also 
 Abhandl. d. math.-phys. Klasse d. Konig.-Sachs. Gesellsch. d. Wissensch., Bd. XV, 1889. 
 
 His, W.: Die Entwickelung des menschlichen Rautenhirns vom Ende des ersten bis zum 
 Beginn des dritten Monats. I. verlangertesMark. Abhandl. d. math.-phys. Klasse d. Konig.- 
 Sachs. Gesellsch. d. Wissensch., Bd. XVII, 1891. 
 
 His, W.: Die Entwickelung des menschlichen Gehirns wahrend der ersten Monate. 
 Leipzig, 1904. 
 
 JOHNSTON, J. B.: The Nervous System of Vertebrates. 1906. 
 
 KOLLMANN, J.: Handatlas der Entwickelungsgeschichte des Menschen. Bd. II, 1907. 
 
 VON KUPFFER, K. : Die Morphogenie des Centralnervensystems. In Hertwig 's Handbuch 
 d. vergleich. u. experiment. Entwickelungslehre der Wirbeltiere. Bd. II, Teil III, Kap. 8, 
 1905. 
 
 MARBURG, O.: Mikroskopisch-topographischer Atlas des menschlichen Zentralnerven- 
 sy stems, 1904, 
 
 MEYER, A.: Critical Review of the Data and General Methods and Deductions of 
 Modern Neurology. Jour. o/Comp. N enrol., Vol. VIII, Nos. 3 and 4, 1898. 
 
 NEUMAYER, L.: Histo- und Morphogenese des peripheren Nervensystems, der Spinal- 
 ganglien und des Nervus sympathicus. In Hertwig's Handbuch der vergleich. und experi- 
 ment. Entwickelungslehre der Wirbeltiere, Bd. II, Teil III, Kap. 10, 1906. 
 
 RAMON Y CAJAL, S. : Sur Porigine et les ramifications des fibres nerveuses de la moelle 
 embryonnaire. Anat. Anz., Bd. V, Nos. 3 and 4, 1890. 
 
 RAMON Y CAJAL, S. : A quelle epoque apparaissent les expansions des cellules nerveuses 
 de la moelle epiniere du poulet? Anat. Anz., Bd. V, Nos. 21 and 22, 1890. 
 
 RAMON Y CAJAL, S.: Textura del sistema nervioso del hombre y de los vertebrados. 
 Madrid, 1899-1904. Also translation into French by Azoulay, 1910-11. 
 
 RAMON Y CAJAL, S.: Nouvelles observations sur 1'evolution des neuroblasts, avec quel- 
 ques remarques sur Phypothese neurogenetique de Hensen-Held. Anat. Anz., Bd. XXXII, 
 Nos. i, 2, 3 and 4, 1908. 
 
 SCHAPER, A.: Die morphologische und histologische Entwickelung des Kleinhirns der 
 Teleostier. Morph. Jahrbuch, Bd. XXI, 1894. 
 
 SCHAPER, A.: Die friihesten Differenzierungsvorgange im Centralnervensystems. Arch. 
 f. Entw.-Mechan., Bd. V, 1897. 
 
 SMITH, G. E.: On the Morphology of the Cerebral Commissures in the Vertebrata, etc. 
 Trans. Linncean Soc. of London, 2d Ser. Zoology, Vol. VIII, Part 12, 1903. See also articles 
 by same author in Jour, of Anat. and Physiol. 
 
 STREETER, G. L.: The Development of the Cranial and Spinal Nerves in the Occipital 
 Region of the Human Embryo. Am. Jour, of Anat., Vol. IV, No. i, 1904. 
 
 STREETER, G. L. : The Peripheral Nervous System in the Human Embryo at the End 
 of the First Month. Am. Jour, of Anat., Vol. VIII, No. 3. 
 
 ZIEHEN, TH. : Die Morphogenie des Centralnervensystems der Saugetiere. In Hertwig's 
 Handbuch der vergleich. u. experiment. Entwickelungslehre der Wirbeltiere. Bd. II 5 Teil III, 
 Kap. 8, 1905. 
 
 ZIEHEN, TH.: Die Histogenese von Him- und Riickenmark. Entwickelung der 
 Leitungsbahnen und der Nervenkerne bei den Wirbeltierer. In Hertwig's Handbuch def 
 vergleich. u. experiment Entwickelungslehre der Wirbeltiere, Bd. II, Teil III, Kap. IX, 1905, 
 
CHAPTER XVIII. 
 
 THE ORGANS OF SPECIAL SENSE. 
 THE EYE. 
 
 The receptive mechanisms of all the general and special sense organs 
 are derived from the ectoderm. With the single exception of the eye, all 
 develop as direct specializations of the ectoderm in the form of the various 
 neuro-epithelia. The eye is peculiar among the sense organs in that its recep- 
 tive cells are not derived directly from surface ectoderm, but only indirectly from 
 the ectoderm after it has become folded in to form the neural canal. The 
 neuro-epithelium of the eye develops as a direct outgrowth from the central 
 nervous system. The retina is a modified part of the brain; the optic nerves 
 correspond to central nervous system fiber tracts. Of the accessory optic 
 structures, the lens, the epithelium of the lids and conjunctiva, the eyelashes, 
 the Meibomian glands and the epithelium of the lacrymal apparatus are of 
 ectodermic origin; the coats of the eye, the sclera and chorioid, and parts of 
 
 Optic Neural Optic 
 
 depression plate depression 
 
 FIG. 494. Diagram showing location of optic areas before the closure of the neural groove. 
 
 Modified from Lange. 
 
 their modified anterior extensions, the cornea, ciliary body and iris, are of 
 mesodermic origin. In the sensory divisions of the other spinal and cranial 
 nerves, with the exception of the olfactory, the cell bodies of the neurones which 
 serve to connect the receptive mechanisms with the brain and cord are located 
 in parts (the sensory ganglia of the cranial and spinal nerves) which have be- 
 come separated from the crests of the neural folds as the latter fuse to form the 
 neural canal. In the eye the cell bodies of these neurones are located in the 
 retina, but the area of ectoderm from which the retina develops first occupies'a 
 position along the neural crest analogous to that occupied by the anlagen of the 
 spinal and cranial ganglia. In the case of the retina this area, instead of be- 
 coming split off in the closure of the neural canal, becomes folded into the 
 canal and later pushed out toward the surface in the optic evagination (Figs. 494, 
 495, 49 6 )- 
 
 563 
 
564 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 The first indication of eye formation is found in the chick at the beginning 
 of the second day of incubation ; in the human embryo, at what has been estimated 
 as about the second or third week. At this stage the neural canal is not yet 
 completely closed in and its anterior end shows three primary brain vesicles 
 
 Optic vesicle area 
 
 Neural canal 
 
 FIG. 495. Diagram showing location of areas shown in Fig. 494 after the formation of the 
 neural canal. Modified from Lange. 
 
 (p. 473, Fig. 497). The anlagen of the eyes first appear as bilaterally sym- 
 metrical evaginations from the lateral walls of the fore-brain vesicle (Figs. 497 and 
 498), and are at first large in proportion to the brain vesicle itself. When 
 first formed, the optic evagination opens widely into the fore-brain vesicle (Fig. 
 498, right side), but as the distal part of the evagination expands more rapidly 
 
 Retina 
 
 H-b, 
 
 Optic stalk 
 
 FIG. 496. FIG. 497. 
 
 FIG. 496. Diagram showing location of the (dark) optic area (see Fig. 495) after the beginning of 
 the formation of the optic cup and optic stalk. Lange. 
 
 FIG. 497. Dorsal view of head of chick of 58 hours' incubation. Mihalkovics. 
 
 Lam. term, lamina terminalis; Fb., fore-brain; Opt. v., optic vesicle; M. b., mid-brain; 
 
 H.b., hind or rhombic brain; H., heart. 
 
 than the proximal part, there soon results a spheroidal optic vesicle attached to 
 the fore-brain by the narrow optic stalk (Fig. 498, left side) . Through the latter 
 the cavity of the optic vesicle and the cavity of the fore-brain are in communi- 
 cation. With the development of the hemispheres, that part of the brain to 
 which the optic stalks are attached becomes the inter-brain (diencephalon). 
 
THE ORGANS OF SPECIAL SENSE. 
 
 565 
 
 The Lens. As each optic vesicle grows out toward the surface, its outer 
 wall soon comes to lie just beneath the surface ectoderm. The cells of that 
 portion of the ectoderm which overlies the optic vesicle next proliferate and 
 cause a thickening of the ectoderm (Fig. 498, left side). This thickening of the 
 
 Fore-brain vesicle 
 
 Lens area - 
 
 Optic vesicle 
 
 Surface ectoderm 
 
 Optic vesicle 
 
 FIG. 498. Section through head of chick of two days' incubation. Duval. 
 
 The formation of the optic vesicle and stalk appears to be somewhat more advanced 
 
 on the left than on the right. 
 
 ectoderm over the optic vesicle is apparent in the chick embryo of 36 hours in- 
 cubation; in the human embryo it occurs about the third or fourth week and 
 represents the first step in the development of the crystalline lens. The thick- 
 ened portion of ectoderm is known as the lens area (Fig. 498). The latter next 
 
 Fore-brain 
 
 Lens in vagination -gil HT: - f ^k' '.$ M'^'I* Len s invagination 
 
 Optic vesicle 
 
 Optic vesicle 
 
 FIG. 499. Section through head of chick of three days' incubation. Duval. 
 
 becomes depressed against the outer surface of the optic vesicle forming a 
 distinct lens invagination (Fig. 499). This becomes cup-shaped and then its 
 edges come together and fuse, thus forming the lens vesicle (Fig. 500) . At first the 
 lens vesicle is connected with the surface ectoderm, but about the eighth week 
 
566 TEXT-BOOK OF EMBRYOLOGY. 
 
 a thin layer of mesoderm grows in between the lens vesicle and the surface 
 ectoderm, completely separating them (Fig. 501). The ingrowth of the lens 
 vesicle against the outgrowing optic vesicle has the effect as though a small hard 
 ball (the lens vesicle) had been pressed into a larger soft ball (the optic vesicle) 
 
 Fore-brain 
 
 FIG. 500. Showing somewhat later stage in development of optic cup and lens 
 than is shown in Fig. 499. Duval. 
 
 (Fig. 502). The lens vesicle pushes the outer wall of the optic vesicle in against 
 the inner wall, the optic vesicle thus becoming transformed into the two-layered 
 optic cup (Figs. 500, 501). Bonnet calls attention to the fact that the two proc- 
 esses, lens formation and the invagination of the optic vesicle to form the optic 
 
 Conjunctival epithelium --- 
 
 Vitreous 
 
 Retina (inner layer 
 of optic cup) 
 
 Pigmented layer of retina 
 (outer layer of optic cup) 
 
 FIG. 501. Diagram of developing lens and optic cup. Duval. 
 
 The cells of the inner wall of the lens vesicle have begun lo elongate to form lens fibers. The epi- 
 thelium over the lens is the anlage of the corneal epithelium. The mesodermal tissue between 
 the latter and the anterior wall of the lens vesicle is the anlage of the substantia propria 
 corneae. 
 
 cup, are more or less independent and that it is not correct to describe the lens as 
 actually pushing in the outer wall of the vesicle. As evidence of this is noted 
 the fact that typical optic cup formation may occur in cases where no lens is 
 developed. The optic cup when first formed is not a complete cup, for the 
 
THE ORGANS OF SPECIAL SENSE. 567 
 
 imagination of the optic vesicle is carried over along the posterior surface of the 
 optic stalk forming the chorioidal fissure (Fig. 502, see also p. 575). 
 
 The lens area is thicker at its center than at its periphery and when the 
 center of the lens area becomes the bottom of the lens depression and later 
 the posterior wall of the lens vesicle this greater thickness is maintained. In 
 fact, the posterior wall of the vesicle becomes still thicker so that it projects into 
 the cavity of the lens vesicle as an eminence (Fig. 503, g.) . In the chick the lens 
 vesicle is hollow. In man and in Mammals generally it is more or less filled 
 with cells. These, however, degenerate and take no part in the formation of the 
 
 Pigmented layer of retina Nervous layer of retina 
 
 (outer layer of optic cup) (inner layer of optic cup) 
 
 Cavity of 
 optic vesicle ^ ^ ___*_ 
 
 Rim of optic cup. 
 
 Optic furrow 
 
 Lens 
 
 Hyaloid artery I Optic furrow 
 
 Hyaloid artery entering 
 cavity of vitreous 
 
 FIG. 502. Model showing lens and formation of optic cup. A piece has been removed from the 
 upper part of cup to show the cavity of the optic vesicle and the position of the inner layer 
 of the cup (nervous layer of retina) . Bonnet. 
 
 permanent lens. Comparing the posterior with the anterior wall of the lens at this 
 stage, the latter is seen to be composed of a single layer of cuboidal cells, the an- 
 lage of the anterior epithelium of the lens (Figs. 501 , 503 , g, h, i) . This layer passes 
 over rather abruptly into the posterior wall which consists of a single layer of 
 greatly elongated lens cells, the anlagen of the lens fibers. The lens fibers con- 
 tinue to elongate until by the end of the second month they touch the anterior 
 epithelium, thus completely obliterating the cavity of the lens vesicle (Fig. 505). 
 A small cleft containing a few drops of fluid, the liquor Morgagni, may remain 
 between the anterior epithelium and the lens fibers. 
 
 When the lens fibers are first formed, the longest fibers are in the center and 
 the fibers gradually get shorter toward the periphery of the lens where they pass 
 over into the anterior epithelium (Fig. 503), As the lens develops, the periph- 
 
568 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 eral fibers elongate more rapidly than the central, with the result that in the fully 
 developed lens the central fibers are the shortest, forming a sort of core around 
 which the now longer peripheral fibers extend in much the same manner as the 
 layers of an onion (Fig. 505) . The ends of the fibers meet on the anterior and 
 posterior surfaces of the lens, along more or less definite lines which can be seen 
 
 FIG. 503. Successive stages in the development of the lens in the rabbit embryo. Rdbl. 
 
 a, b, c, d, and e, are from embryos of from n| to 12 days; f, at end of i2th day; g, during the i3th 
 
 day; h, between the i3th and i4th days; i, from an embryo of n mm. 
 
 on surface examination and which are known as sutural lines. The lens fibers 
 are at first all nucleated and as the nuclei are situated at approximately the same 
 level in all the fibers, there results a so-called nuclear zone (Fig. 503, i). Later 
 the nuclei disappear. The sutural lines become evident about the fifth month 
 and mark the completion of the lens formation, although lens fibers continue 
 to be formed throughout foetal and in postnatal life, probably by proliferation 
 
THE ORGANS OF SPECIAL SENSE 569 
 
 and differentiation of the cells of the anterior epithelium, in the region where the 
 latter pass over into the lens fibers. (The successive stages in the development 
 of the lens are shown in Fig. 503.) 
 
 The lens capsule becomes differentiated during the third month. It is con- 
 sidered by some as derived from the lens epithelium and of the nature of a 
 cuticular membrane, by others as a product of the surrounding connective 
 tissue. 
 
 By the extension of mesodermic tissue in between the lens and the surface 
 ectoderm, the lens becomes by the end of the sixth week completely surrounded 
 by a layer of vascular connective tissue. This is known as the tunica vasculosa 
 lentis, and receives its blood supply mainly from the hyaloid artery (Fig. 505) 
 which is a foetal continuation of the arteria centralis retina (p. 575). Branches 
 from the hyaloid artery break up into a capillary network which covers both 
 anterior and posterior surfaces of the lens. That part of the tunica vasculosa 
 which covers the anterior surface of the lens is known as the membrana pupillaris. 
 After the earlier and more rapid formation of lens fibers ceases, the hyaloid 
 artery begins (about the seventh month) to undergo regressive changes, and at 
 birth is normally absent. Rarely more or less of the tunica vasculosa fails to 
 degenerate, and if the part w r hich persists is the membrana pupillaris there 
 results a malformation known as congenital atresia of the pupil. 
 
 The Optic Cup. The w^ay in which the optic vesicle becomes transformed 
 into the optic cup has been partially described in considering the development of 
 the lens (p. 566) . The growing lens vesicle appears to push in the outer wall of 
 the optic vesicle while at the same time the edges of the latter are extending 
 around the lens vesicle, until w r hat was originally the outer wall of the optic 
 vesicle lies in apposition with the original inner wall, the cavity of the primary 
 optic vesicle thus becoming completely obliterated (Fig. 504). In this way the 
 optic vesicle is transformed into a two-layered thick-w r alled cup, the cleft be- 
 tween the two layers corresponding to the cavity of the primary vesicle. This 
 cup is at first entirely filled with the developing lens (Fig. 504) . As the cup in- 
 creases in size faster than the lens, the contiguous walls of the cup and lens 
 become separated, the cavity thus formed being the cavity of the vitreous 
 humor (Fig. 505). There seems to be no question but that in Mammals a 
 small amount of mesoderm at first separates the optic evagination from the lens 
 area of the surface ectoderm. This apparently disappears, however, so that 
 the two are in direct contact. It is still an open question whether a thin layer 
 of mesoderm grows in between the edges of the cup and the lens at or just before 
 the beginning of the formation of the vitreous. The lens now no longer fills the 
 optic cup but lies in the mouth of the cup, while at the same time the margin 
 of the cup is extending somewhat over its outer surface, where with the meso- 
 derm it ultimately gives rise to the ciliary body and iris, and forms the 
 
570 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 boundary of the pupil. The remainder of the two-walled optic cup becomes 
 the retina. 
 
 The Retina. Of the two layers which form the wall of the optic cup (p. 569) , 
 the outer (away from the cavity) forms thepigmented layer, while the inner forms 
 the remainder of the retina (Figs. 501, 505). Soon after the formation of the 
 optic cup, it is possible to distinguish a boundary zone the future or a serrata 
 between the larger posterior part of the retina or nervous retina and the smaller 
 anterior non-nervous part which becomes the retinal portion of the ciliary body 
 
 Vascular mesoderm 
 
 [Remains of optic 
 vesicle cavity 
 
 Ectoderm 
 
 Lens anlage 
 Lens invagination 
 
 Pigmented layer of retina 
 (outer layer of optic cup) 
 
 Vascular mesoderm 
 Wall of brain vesicle 
 
 FIG. 504. Section through optic cup and lens invagination of chick of fifty-four 
 
 hours' incubation. Lange. 
 
 Between the lens anlage and the pigmented layer of the retina is the broad inner layer of the optic 
 cup, the anlage of the remainder of the retina. 
 
 and iris. While the optic cup is forming, its two layers are both rapidly in- 
 creasing in thickness by mitotic division of their cells. Especially is this true of 
 the inner layer over that region which is to become the nervous retina, and it is 
 the rather abrupt transition between the thicker nervous retina and the com- 
 paratively thin non-nervous anterior extension of the retina that forms the ora 
 serrata. 
 
 The invagination which gives rise to the two-layered optic cup thus differen- 
 tiates what may be called the two primary layers of the retina, the pigmented layer, 
 and a broad layer from which are to develop all the other layers of the retina. 
 
THE ORGANS OF SPECIAL SENSE. 
 
 571 
 
 (Figs. 501 , 505) . Further development consists in a gradual differentiation, within 
 the broad layer, of the various retinal elements and consequent demarcation of the 
 layers which constitute the adult retina. The next layer to differentiate is the 
 innermost layer of the retina, or layer of nerve fibers. This appears during the 
 sixth or seventh week as a thin, clear, faintly striated zone containing a few 
 scattered nuclei. What remains of the original inner layer of the cup has now 
 become a comparatively thick layer with numerous chromatic and actively 
 dividing nuclei. It may be conveniently designated the primitive nuclear layer. 
 
 Surface epithelium 
 
 of eyelid 
 
 Eyelid (upper) 
 
 Corneal epithelium 
 
 Conjunct! val 
 
 epithelium 
 
 Substantia 
 
 propria corneae 
 
 Lens 
 
 Anterior epithe- 
 lium of lens 
 
 Conjunctival sac 
 
 Chorioid 
 Pigmented layer 
 of retina 
 Split between 
 retinal layers 
 Retina, except 
 pigmented layer 
 Vitreous 
 
 Tunica vasculosa 
 
 lentis 
 
 Nerve fiber layer 
 
 of retina 
 
 Hyaloid artery 
 
 Central artery 
 of retina 
 
 Optic nerve 
 
 FIG. 505. Horizontal section through eye of human embryo of 13-14 weeks. Modified from Lange. 
 
 The similarity in development between the retina and wall of the neural tube 
 is to be noted. Thus the layer of nerve fibers appears to correspond quite 
 closely to the marginal layer of the central nervous system, while the primitive 
 nuclear layer is probably homologous with the mantle layer (pp. 479, 485). 
 There is a similar correspondence between the retina and the central nervous 
 system in regard to their early cellular development, the retinal cells early 
 showing a differentiation into neuroblasts and spongiobiasts (pp. 479, 485). 
 
 About the end of the eighth week the inner part of the primitive nuclear 
 layer differentiates into the layer of ganglion cells (Fig. 506, It). These 
 are large cells and with their processes constitute the third or proximal optic 
 neurone. They can be first distinguished in the fundus of the cup and gradu- 
 ally extend to the ora serrata. They are the first of the cellular elements of the 
 adult retina which can be definitely recognized as such. From each cell, two 
 kinds of processes develop, dendrites, which ramify in this and in the more 
 external layers of the retina, and an axone which grows toward the cavity of 
 the eye and becomes a fiber of the layer of nerve fibers, whence it continues into 
 
572 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 the optic stalk as one of the fibers of the optic nerve. The layer of ganglion cells 
 is thickest in an area situated somewhat lateral to the attachment of the optic 
 stalk and known as the area centralis. It is distinguishable about the end of the 
 fourth month. In the center of the area centralis the retinal layers become 
 thin to form ihefovea centralis which develops toward the end of fcetal life. 
 The macula lutea with its yellow pigment does not develop until after birth. 
 The retina at this stage thus consists of four layers which from within out- 
 ward are (i) the layer of nerve fibers, (2) the layer of ganglion cells, (3) the 
 nuclear layer, (4) the pigmented layer (see Fig. 507) . 
 
 FIG. 506. Diagram of the development of the retinal cells. Kallius, after Cajal. 
 a, Cone cells in unipolar stage; b, cone cells in bipolar stage; c, rod cells in unipolar stage; d, rod cells 
 in bipolar stage; e, bipolar cells; /and i, amacrine cells; g, horizontal cell; h, ganglion cells; 
 k, Muller's cells or fibers; I, external limiting membrane. 
 
 The further development of the retina consists largely of a differentiation of 
 the cells of the nuclear layer. This is extremely complex and our knowledge 
 of it meager. From the cells of this layer develop (i) the rod and cone cells, (2) 
 the bipolar cells, (3) the tangential or horizontal cells, (4) the amacrine cells, (5) 
 Muller's cells or fibers. The differentiation of these cells and their processes 
 also results in the demarcation of the following layers of the adult retina; (i) the 
 layer of rods and cones, (2) the outer limiting membrane, (3) the outer nuclear 
 layer, (4) the outer molecular layer, (5) the inner nuclear layer, (6) the inner 
 molecular layer, (7) the inner limiting membrane (see Fig. 508). 
 
 Muller's cells or the sustentacular cells (Fig. 506, k) develop from spongio- 
 blasts which lie toward the inner limit of the nuclear layer. This accounts 
 for the location of the nucleated portions of Muller's cells. Processes of these 
 cells grow toward both surfaces of the retina until they reach the positions of the 
 future outer and inner limiting membranes where they are believed to spread out 
 
THE ORGANS OF SPECIAL SENSE. 573 
 
 horizontally and unite to form these membranes. Other spongioblasts develop 
 into other types of glia cells, mainly spider cells, which are most numerous in 
 the layer of ganglion cells and in the layer of nerve fibers. 
 
 The rod and cone cells are first recognizable as unipolar cells (Fig. 506,0, c). 
 The single process of each extends outward as far as the outer limiting mem- 
 brane. About as soon as these cells are recognizable, a differentiation between 
 the rod cells and the cone cells can be made by their reactions to the Golgi 
 silver stain, the cone cells impregnating much more completely than the rod 
 cells. Processes next grow out from the inner ends of the cells so that they 
 become bipolar (Fig. 506, b, d). Both rod and cone cells are at first distributed 
 throughout the entire nuclear layer, but later they become arranged in a dis- 
 tinct layer just beneath the outer limiting membrane. Each cell next gives 
 rise to or acquires at its outer end an expansion which extends through 
 
 Layer of nerve fibers 
 Layer of nerve cells 
 Inner molecular layer 
 Inner nuclear layer 
 
 w;ww? 
 inpfiK^ 
 
 KFJzras^ 
 
 nil 
 
 Outer undifferentiated layer 
 
 FIG. 507. Vertical section through retina of a four months' human embryo. Modified from Lange* 
 
 the outer limiting membrane into the pigmented layer. As the pigmented 
 cells give off pigmented processes which extend inward among the outer 
 ends of the rods and cones, the layer of retina just beneath the pig- 
 mented layer consists of the outer ends of the rod cells, the tips of the cone 
 cells, and the extensions of the pigmented cells. The nucleated portions of 
 the rod and cone cells form the outer nuclear layer. Though the layer of rods 
 and cones and the outer nuclear layer present the appearance in haematoxylin- 
 eosin stained specimens of two distinct layers, it is evident from their develop- 
 ment and structure that they should be regarded as a single neuro- epithelial 
 layer. The apparent separation into two layers is due to the interposition of the 
 outer limiting membrane, through tiny holes in which the rod and cone cells 
 extend. The inwardly directed processes of the rod and cone cells are their 
 axones. These cells constitute the first or distal optic neurone. 
 
 The bipolar cells (Fig. 506, e), which with their processes constitute the 
 middle or second optic neurone, also develop from cells of the nuclear layer 
 
574 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
 and are probably bipolar at the time that the rod and cone cells are in the 
 unipolar condition. Reference to the two bipolar cells shown in Fig. 506, e, e, 
 shows that at this stage in their development their outwardly directed processes 
 extend to the outer limiting membrane. These processes must either actually 
 shorten or else fail to grow in length proportionately as the retina increases in 
 thickness, for in the mature retina they end in relation with the centrally 
 (inwardly) directed processes (axones) of the rod and cone cells. According as 
 they are in relation with rod cells or cone cells, they are known as rod bipolars 
 or cone bipolars. The retinal layer in which the axones of the rod and cone 
 
 Inner limiting membrane 
 
 Layer of nerve fibers 
 Layer of nerve cells 
 
 Inner molecular layer 
 
 ( horizontal cells 
 
 Inner nuclear layer ^ bipolar cells 
 (amacrine cells 
 
 Outer molecular layer 
 Outer nuclear layer 
 
 Outer limiting membrane 
 Layer of rods and cones 
 
 Layer of pigmented epithelium 
 
 FIG. 508. Vertical section through retina of a five and one-half months' human embryo. 
 
 Modified from Lange. 
 
 cells and the dendrites of the rod and cone bipolars intermingle is the outer 
 molecular layer of the adult retina. It is first distinctly recognizable as a mo- 
 lecular layer about the end of the fifth month (Fig. 508). 
 
 The development of the outer molecular layer separates the originally single 
 nuclear layer into two layers, an outer composed of the nuclei of the rod and cone 
 cells and an inner composed of the nucleated bodies of the rod and cone 
 bipolars, of the horizontal cells (Fig. 506, g) and of the amacrine cells (Fig. 506, 
 / and i), all of which can be recognized in Golgi specimens by the end of the 
 seventh month. The rod and cone bipolars and probably most of the other 
 cells of the inner nuclear layer send their axones centrally to lie in contact with 
 the dendrites and bodies of the ganglion cells. 
 
THE ORGANS OF SPECIAL SENSE. 575 
 
 With the development of the cells of the inner nuclear layer and their proc- 
 esses, there differentiates the inner molecular layer which separates the inner 
 nuclear layer and the layer of ^ganglion cells. It consists mainly of ramifica- 
 tions of the dendrites and axones of cells the bodies of which lie in the inner 
 nuclear layer and in the layer of ganglion cells. (Fig. 508.) 
 
 The Chorioid and Sclera. These develop wholly from the mesoderm. 
 The way in which the mesoderm grows in between the lens and the surface and 
 surrounds the optic cup has been described (p. 566). That part of the meso- 
 derm lying immediately external to the retina develops very early a close- 
 meshed capillary network. This appears before there is any definitely limited 
 sclera and may be considered the anlage of the chorioid. Somewhat later the 
 mesoderm which lies just to the outside of the chorioid takes definite shape as the 
 external fibrous tunic of the eye or sclera. 
 
 The Vitreous. The manner in which the vitreous humor is formed has 
 been the subject of much controversy and remains still undetermined. As 
 already noted in describing the development of the lens (p. 585), the latter is at 
 first in direct contact with the inner layer of the retina (Fig. 504) . The lens and 
 the retina separate as the vitreous forms between them. During the develop- 
 ment of the lens the arteria centralis retinas does not stop, as in the adult, 
 with its retinal branches, but continues across the optic cup as the hyaloid 
 artery to end in the vessels of the tunica vasculosa lentis. Some investigators 
 consider the vitreous a transudate from these blood vessels. As the chorioidal 
 fissure closes, some mesodermic tissue is enclosed with the artery, and some 
 investigators consider the vitreous a derivative of this mesoderm. In Birds 
 the formation of the vitreous humor begins before either mesoderm or blood 
 vessels have penetrated the optic cup, and Rabl suggests that the vitreous may 
 be a secretion of the retinal cells. Bonnet describes a double origin of the 
 vitreous, differentiating between a retinal vitreous and a mesoderm vitreous. 
 According to Bonnet, the primary vitreous body begins its formation before the 
 closure of the chorioidal fissure. This primary vitreous appears at the time 
 of formation of the optic cup, is a fibrillated secretion of the retinal cells, and 
 fills in the vitreous space with a feltwork of fine fibrils. With the formation of 
 the optic cup and the closure of the chorioidal fissure this type of vitreous forma- 
 tion ceases and a secondary vitreous body formation takes place from the cells 
 of the pars ciliaris retinae. This is also fibrillated and there develops at this 
 time the so-called hyaloid membrane which closely invests the vitreous. Among 
 the fibers of the vitreous body appears the vitreous humor. Up to this point the 
 vitreous is entirely non-cellular. There next grow into it mesodermal cells 
 which have reached the vitreous through the chorioidal fissure along with the 
 hyaloid artery. To what extent these cells are used up in the formation of the 
 blood vessels of the vitreous and to what extent they remain as connective tissue 
 
576 TEXT-BOOK OF EMBRYOLOGY. 
 
 cells of the mature vitreous after the blood vessels have degenerated is not 
 known. 
 
 As already noted, the vitreous is at first crossed by the hyaloid artery which 
 supplies the developing lens (p. 569). As lens formation becomes less active 
 the artery becomes less important and by the end of the third month begins to 
 atrophy. At birth nothing remains of it, but in its former course the vitreous 
 is somewhat more fluid than elsewhere and this is known as the hyaloid canal 
 (canal of Cloquet). 
 
 The Optic Nerve. Referring to the description of the optic evagination it 
 will be recalled that the optic vesicle maintains its connection with the brain by 
 means of the optic stalk (p. 564). The latter is hollow and connects the cavity 
 of the optic vesicle with the cavity of the brain. When the invagination of the 
 optic vesicle to form the optic cup occurs (p. 566, Fig. 502), the invagination is 
 carried along the posterior surface of the optic stalk toward the brain, and just 
 as the invagination of the optic vesicle results in the obliteration of the cavity 
 of the vesicle, so the invagination of the optic stalk results in an oblitera- 
 tion of its lumen. In Mammals the invagination of the optic stalk extends only 
 part way to the brain, to the point where the artery enters. The chorioidal 
 fissure closes about the seventh week. 
 
 The optic stalk consists of supportive elements only, and serves as a track 
 along which nerve fibers extend to connect the retina and brain. Nerve fibers 
 appear in the optic stalk about the fifth week. They appear first around the 
 periphery and apparently crowd the neuroglia nuclei toward the center, so that 
 the stalk at this stage may be said to consist of a mantle layer and a marginal 
 layer, apparently analogous to these layers in the retina and brain. The nerve 
 fibers gradually invade the entire stalk so that by the end of the third month the 
 stalk has become transformed into the optic nerve among the fibers of which the 
 original supportive elements of the stalk are still represented by neuroglia cells. 
 
 Much difference of opinion has existed in regard to the origin of the optic 
 nerve fibers, whether they are processes of retinal cells which end in the brain 
 or processes of brain cells which end in the retina. It is now quite generally 
 accepted that most of the fibers of the optic nerve are the axones of neurones the 
 cell bodies of which are situated in the ganglion cell layer of the retina. These 
 axones pass centrally into the layer of nerve fibers, which they form, and con- 
 verge toward the optic nerve. Through the latter they pass to their terminations 
 in the external geniculate bodies, optic thalami and anterior corpora quadri- 
 gemina. According to Cajal and others, some centrifugal fibers are present in 
 the optic nerve. These are processes of cells situated in the above-mentioned 
 nuclei, and terminate in the retina. They are fewer in number and of later 
 development than the centripetal fibers. 
 
 As the mesodermic anlagen of the chorioid and sclera are present before 
 
THE ORGANS OF SPECIAL SENSE. 577 
 
 the nerve fibers begin to grow into the optic stalk, the fibers must pass through 
 these two coats in their exit from the eye. There results the fenestrated cross- 
 ing of the optic nerve by these two coats, known as the lamina cribrosa. 
 
 The optic nerve fibers are medullated but have no neurilemmae. They are 
 supported by neuroglia. The connective tissue sheaths which enclose the optic 
 nerve are direct extensions of the meninges. These structural peculiarities 
 accord with the peculiarities already described in the development of the 
 nerve. Attention has been called to the fact (p. 563) that just as the retina 
 should be considered a modified and displaced portion of the central nervous 
 system of brain cortex so the optic nerve should be considered not as a 
 peripheral nerve, but as analogous to a central nervous system fiber tract. 
 
 The Ciliary Body, Iris, Cornea, Anterior Chamber. Anteriorly where 
 they come into relation with the lens and are so arranged as to admit light to the 
 retina, all three coats of the eye are extensively modified. Thus the retina is 
 continued anteriorly as the pars ciliaris retinae and pars iridica retinae, the 
 chorioid as the stroma of the ciliary body and iris, the sclera as the cornea. 
 
 THE CILIARY BODY AND IRIS. Both primary retinal layers (the two layers 
 of the optic cup) are continued anteriorly as the non-nervous retinal layer 
 of the ciliary body and iris. The outer pigmented layer consists at first of 
 several layers of pigmented cells, but later becomes reduced to a single layer 
 of pigmented cells which do not, however, possess pigmented processes extend- 
 ing inward as do the analogous cells of the nervous retina. The abrupt tran- 
 sition at the ora serrata where the thick pars optica retinae passes over into the 
 pars ciliaris retinae has been mentioned (p. 570). The inner layer of the primi- 
 tive retina (optic cup) extends over the ciliary body and iris as a single layer of 
 cells. These remain non-pigmented over the ciliary body, but over the iris 
 acquire pigment so that the two layers form the pigmented layer of the iris. 
 
 The mesodermic tissue which forms the stroma of the ciliary body and iris 
 is derived from the mesoderm lying between the lens and the surface ectoderm. 
 This separates into two layers enclosing between them the anterior chamber of 
 the eye, and it is from the posterior of these tw r o layers that mesodermic tissue 
 extends into the ciliary body and iris. It is continuous with the mesoderm of 
 the tunica vasculosa lentis. During the fourth month the ciliary body under- 
 goes foldings to form the ciliary processes. These foldings at first involve 
 also the iris, but the iris folds soon (end of fifth month) disappear, while the 
 ciliary processes become more prominent. 
 
 Of the smooth muscle tissue found in the ciliary body and iris, the dilator 
 and contractor pupillae are, according to Bonnet, derived from the cells of the 
 pigmented layer of the retina, i.e., from ectoderm. The ciliary muscle, on the 
 other hand, develops from mesoderm. These muscles become well developed 
 during the seventh month. 
 
.578 TEXT-BOOK OF EMBRYOLOGY. 
 
 The suspensory ligament of the lens, or zonula Zinnii, first appears about the 
 end of the fourth month. By some the fibers of the suspensory ligament 
 are believed to differentiate from the vitreous, by others they are considered as 
 derived from the pars ciliaris retinae. Spaces among the fibers of the ligament 
 enlarge and coalesce to form the canal of Petit. 
 
 THE CORNEA. The way in which the mesoderm grows in between the lens 
 vesicle and the surface ectoderm has been described (p. 566). This mesoderm 
 forms a thin almost homogeneous layer containing very few cells. Later that 
 part of the layer which lies against the lens becomes more cellular and vascular, 
 so that it is possible to distinguish between an outer homogeneous non- vascular 
 layer and an inner cellular vascular layer. The former is the anlage of the 
 cornea. Between the two layers vacuoles appear and coalesce to form the 
 anterior chamber of the eye or cavity of the aqueous humor. Subsequent 
 growth of the iris subdivides this chamber into an anterior and a posterior 
 portion. The chamber separates the cornea from the pupillary membrane 
 portion of the tunica vasculosa lentis. Bounding the chamber anteriorly and 
 so forming the posterior layer of the cornea there develops a single layer of 
 flat cells, the so-called " endothelium" of Descemet. Over the surface of the 
 cornea the ectoderm remains and gives rise to a stratified squamous epithelium 
 four to eight cells thick, the anterior corneal epithelium. Just beneath the 
 epithelium a layer of corneal tissue retains its original homogeneous character 
 and forms the anterior elastic membrane or membrane of Bowman. The 
 posterior elastic membrane or membrane of Descemet is usually considered a 
 cuticular derivative of the " endothelium.'' Throughout the rest of the cornea 
 substantia propria cornece cells develop, either by proliferation of the 
 few cells originally present or from cells which grow in from the surrounding 
 cellular mesoderm, and become arranged parallel to the surface as the fixed 
 connective cells of the cornea. 
 
 The Eyelids. After the lens vesicle becomes separated from the surface 
 ectoderm, the latter folds over above and below to form the first rudiments 
 of the upper and lower eyelids. Each fold consists of a core of mesoderm and 
 a covering of ectoderm. From the mesoderm develop the connective tissue 
 elements of the lids including the tarsal cartilage. From the ectoderm develop 
 the epithelial structures of the lids, the epidermis, the eyelashes and the glands. 
 The edges of the lids gradually approach each other and about the beginning 
 of the third month the epithelium of the upper lid becomes adherent to that 
 of the lower, thus completely shutting in the eyeball. This condition obtains 
 until just before birth. 
 
 The eyelashes develop in the same manner as other hairs (p. 447). 
 
 The Meibomian glands, glands of Moll and the lacrymal glands develop, 
 during the period the lids are adherent, as solid cords of ectoderm which giow 
 
THE ORGANS OF SPECIAL SENSE. 579 
 
 into the underlying mesoderm where they ramify to form the ducts and tubules. 
 The anlagen of the ducts and tubules of these glands are thus at first solid cords 
 of cells, their lumina being formed later by a breaking down of the central cells 
 of the cords. 
 
 At the inner angle of the conjunctiva there develops beneath the eyelid 
 folds a third much smaller fold. This becomes the plica semilunaris which 
 in man is a rudimentary structure, but in many of the lower Vertebrates, 
 especially Birds, forms a distinct third eyelid, the so-called nictitating mem- 
 brane. A few hair follicles and sebaceous glands develop in a portion of this 
 fold forming the lacrymal caruncle. 
 
 The Lacrymal Duct. At a certain stage in development, a groove bounded 
 by the maxillary process and the lateral nasal process extends from the eye to 
 the nose (Fig. 136). This is known as the naso-optic furrow. The ectoderm 
 (epithelium) lying along the bottom of this groove thickens about the sixth 
 week and forms a solid cord of cells. As development proceeds and the parts 
 close in, this cord of ectoderm becomes enclosed within the mesoderm, excepting 
 at its ends where it remains connected with the surface ectoderm of the eye and 
 nose, respectively. By a breaking down of the central cells of this cord a lumen 
 is formed and the cord becomes a tube, the lacrymal duct. The primary con- 
 nection of the lacrymal duct is with the upper lid, but while the lumen is being 
 formed an offshoot grows out to the under eyelid to form the inferior branch 
 of the lacrymal duct. 
 
 THE NOSE. 
 
 The anlage of the organ of smell is apparent in human embryos of about 
 three weeks as two thickenings of the ectoderm, one on each side of the naso- 
 frontal process. To these thickenings the term olfactory placodes has been 
 applied (Kupffer). A little later (in embryos of about four weeks), the placodes 
 become depressed below the surface, the depressions themselves being the 
 nasal pits or fossa (see p. 148; also Fig. 123). The placodes, which are 
 destined to give rise to the sensory epithelium, thus come into closer relation 
 with the olfactory lobes of the brain (rhinencephalon) which represent out- 
 growths of the fore-brain (telencephalon) (see p. 501). 
 
 As described in connection with the development of the face, the lateral 
 nasal process arises on the lateral side, the medial nasal process on the medial 
 side, of each nasal pit (p. 148 et seq.; also Fig. 134). Of these processes, the 
 lateral is destined to give rise to the lateral nasal wall and the wing of the nose, 
 the medial to a part of the nasal septum (see p. 148). As development pro- 
 ceeds, the epithelium (ectoderm) of the nasal fossae grows still deeper into the 
 subjacent mesoderm, the fossse thus becoming converted into the nasal sacs, 
 which lie above the oral cavity. According to Hochstetter and Peter, the 
 
580 TEXT-BOOK OF EMBRYOLOGY. 
 
 nasal sacs are not at first in communication with the oral cavity, but lie above, 
 and are separated from it by a plate of tissue which gradually becomes thinned 
 out along the deeper part of the sacs to form the bucco-nasal membrane (Hoch- 
 stetter). Later (in embryos of 15 mm.), the bucco-nasal membrane ruptures 
 and the deep ends of the sacs thus come to open into the mouth cavity, the 
 openings being known as the primitive choanen. In front of the primitive 
 choanen, the nasal passages (formerly the nasal sacs) are separated from 
 the mouth cavity by a plate of tissue, known as the primitive palate (Fig. 509). 
 The latter is produced by the fusion of the maxillary process with the lateral 
 and medial nasal processes (see p. 148), the outer nares thus being somewhat 
 separated from the border of the mouth. 
 
 The further separation of the nasal passages from the oval cavity has been 
 described in connection with the development of the mouth (p. 317) and the 
 
 Lateral nasal process 
 
 Outer nasal opening 
 
 Maxillary process 
 
 Eye 
 
 Primitive choanen 
 
 Palatine process 
 
 FIG. 509. From a model of the anterior part of the head of a 15 mm. human embryo. The lower 
 jaws (mandibular processes) have been removed. Peter. 
 
 development of the palatine processes of the maxillae. It may be repeated 
 briefly, however, that from each maxillary process a horizontal extension grows 
 across between the oral and nasal cavities until it meets and fuses with its fellow 
 of the opposite side and with the nasal septum in the medial line, thus forming 
 the palate which is continuous with the primitive palate mentioned above. 
 (See Figs. 178 and 510.) In this way the nasal cavities or chambers become 
 separated from the oral cavity, but remain in communication with the pharyn- 
 geal cavity through the posterior nares. 
 
 The nasal cavities increase enormously in size and the epithelial surface in 
 extent, owing to (i) the formation of the palate alluded to above, (2) the develop- 
 ment of the nasal concha which has been described on page 192, and (3) the 
 development of accessory cavities maxillary, frontal and sphenoidal sinuses, 
 which represent evaginations, so to speak, from the nasal cavities. 
 
 Probably correlated with the above-mentioned increase in extent of the 
 nasal chambers is the fact that in lung-breathing Vertebrates the chambers 
 
THE ORGANS OF SPECIAL SENSE. 
 
 581 
 
 have acquired a secondary function. In these forms the nose is not only an 
 apparatus for receiving olfactory stimuli, but also serves to convey air to and 
 from the lungs; it is in a sense' a respiratory atrium. The sensory epithelium 
 which the olfactory nerves supply is limited to relatively small areas in the supe- 
 rior conchae and nasal septum. Stratified columnar ciliated epithelium lines all 
 other parts of the cavities. 
 
 Studies on the development of the olfactory nerve have led to diverse 
 opinions, but the investigations of His and Disse go to show that the fibers 
 are processes of cells derived from the thickened ectoderm or olfactory placodes. 
 In human embryos of about four weeks some of the cells in the upper part of 
 the nasal fossa become modified to form the neuro-epithelium. From the 
 
 Jacobson's organ 
 Inferior concha 
 
 Jacobson's cartilage 
 
 Palatine process 
 
 Nasal septum 
 
 Nasal cavity 
 
 Oral cavity 
 
 FIG. 510. From a section through the head of a human embryo of 28 mm., showing the nasal 
 septum, the nasal cavities, the oral cavity, and the palatine processes. Peter. 
 
 peripheral pole of each cell a short slender process grows out to the surface of 
 the epithelium. From the opposite pole a slender process (the axone) grows 
 centrally until it penetrates the olfactory lobe, where it ends in contact with the 
 dendrites of the first central neurone of the olfactory tract. Most of these cells 
 remain in the epithelial layer, but a few wander into the subjacent mesoderm 
 and become bipolar cells which resemble the bipolar cells of the embryonic 
 posterior root ganglia (p. 502). Other epithelial cells of the nasal fossa are 
 converted into the sustentacular cells of the olfactory areas. 
 
 Jacobson's organ arises at the beginning of the third month as a small out- 
 pocketing of the epithelium on the lower anterior part of the nasal septum 
 (Fig. 510). This evagination grows backward as a slender sac along the nasal 
 septum for a distance of several millimeters and ends blindly. In the adult 
 the sac degenerates and often disappears. In some of the lower Mammals 
 
582 TEXT-BOOK OF EMBRYOLOGY. 
 
 Jacobson's organ develops to a greater degree, and some of the epithelial cells 
 send out processes which pass to the olfactory lobes. 
 
 THE EAR. 
 
 The ear of higher Vertebrates consists of three parts the internal, middle, 
 and external. Of these, the internal is the sensory portion proper and, so far 
 as the epithelial elements are concerned, is of ectodermal origin, but secondari!? 
 becomes embedded in the subjacent mesoderm. It constitutes a complicated 
 and highly specialized structure for the reception of certain stimuli that are to be 
 conveyed to the central nervous system. From a functional standpoint it may 
 be divided into the portion composed of the semicircular canals and their ap- 
 pendages, which is concerned in receiving and transmitting stimuli destined 
 
 Rh. br. 
 
 End. ap. 
 Aud. ves. 
 
 Co. gang. 
 
 FIG. 511. Half of a transverse section through the region of the developing ear of a sheep 
 
 embryo of 13 mm. Bottcher. 
 
 Aud. ves., Auditory vesicle; Co. gang., cochlear ganglion; End. ap., endolymphatic 
 appendage; Rh.br., rhombic brain. 
 
 for the static and equilibration centers in the central nervous system, and the 
 cochlear portion, which is concerned in receiving and transmitting auditory 
 stimuli. The middle and outer ear represent modified portions of the most 
 cranial of the branchial arches and grooves, and constitute an apparatus for 
 conducting sound waves to the cochlear portion of the inner ear. 
 
 The Inner Ear. In embryos of 2 to 4 mm., the ectoderm becomes some- 
 what thickened over a small area lateral to the still open neural groove in the 
 region of the future hind-brain. This thickening is often spoken of as the 
 auditory placode (see p. 499). Owing to more rapid growth of the cells in the 
 deeper layers of the placode, it soon becomes converted into a cup-shaped 
 depression which is known as the auditory pit. The edges of the pit fold 
 in and fuse and the pit thus becomes the auditory vesicle (otocyst), which 
 finally becomes constricted from the parent ectoderm and lies free in the sub- 
 jacent mesoderm (Fig. 511). 
 
THE ORGANS OF SPECIAL SENSE. 583 
 
 At this stage (embryos of 4 to 5 mm.) the auditory vesicle is an oval or 
 spherical sac the wall of which consists of two or three layers of undifferen- 
 tiated epithelial cells. It lies against the neural tube and is connected with the 
 latter by the acoustic ganglion (Fig. 512, a). About the same time an evagina- 
 tion appears on the dorsal side of the auditory vesicle, forming the anlage of the 
 endolymphatic appendage (Fig. 512, a, b, c). The evagination continues to 
 elongate and comes to form a club-shaped structure, the distal end of which 
 becomes flattened to form the endolymphatic sac, the narrower proximal portion 
 constituting the endolymphatic duct (Fig. 512 a-ri). The epithelium, which at 
 first consisted of two or three layers of cells, becomes reduced to a single layer. 
 In the chick the endolymphatic appendage is formed out of the original union 
 between the ectoderm and the auditory vesicle (Keibel, Krause). In Reptiles 
 and Amphibia (Peter, Krause) and in man (Streeter), on the other hand, this 
 appendage develops independently of the union, appearing on the dorsal side of 
 the seam of closure in the auditory vesicle. 
 
 In embryos of about 6 mm. the auditory vesicle (apart from the endolymph- 
 atic appendage) becomes differentiated into two portions or pouches a bulging, 
 triangular one above, which is connected with the endolymphatic appendage, 
 and a more flattened one below. The former is the vestibular pouch, the latter 
 the cochlear pouch (Fig. 512, b-f). Between the two is a portion of the vesicle 
 which is destined to give rise to the saccule and utricle, and which may be called 
 the atrium (Streeter). Properly speaking, the atrium is a division of the 
 vestibular pouch. The cochlear pouch is phylogenetically a secondary diver- 
 ticulum which develops from the atrium, appearing first in the lowest land- 
 inhabiting Vertebrates (Amphibia). 
 
 As mentioned above, the vestibular pouch early assumes the form of a 
 triangle, with the apex toward the endolymphatic appendage. The three 
 borders of the triangle form the anlagen r of the semicircular canals and bear the 
 same interrelation as the latter. At the same time a vertical groove (the lateral 
 groove) appears between the anlage of the posterior canal and the posterior end 
 of the lateral canal (Fig. 512, b, d). 
 
 The formation of the semicircular canals is shown in Fig. 512, g-k. The 
 edges of the triangular vestibular pouch expand and become more or less 
 crescentic in shape. The two walls in the concavity of each crescent come 
 together and then break away (Fig. 512, g, j, absorp.focus), thus leaving the rim 
 of the crescent as a canal attached at its two ends to the utricle. The breaking 
 away affects first the superior, then the posterior, and finally the lateral canal. 
 During these gross changes the epithelium becomes reduced to a single layer 
 of cells. 
 
 At one end of each canal an enlargement appears to form the ampulla, as 
 shown in Fig. 512, /, m, n, and Fig. 513, a, b, c. 
 
584 
 
 TEXT-BOOK OF EMBRYOLOGY. 
 
THE ORGANS OF SPECIAL SENSE. 
 
 585 
 
586 TEXT-BOOK OF EMBRYOLOGY. 
 
 The utricle and saccule represent divisions of the portion of the vestibular sac 
 which is known as the atrium, and into which the endolymphatic appendage 
 and cochlea open (see p. 583) . In embryos of about 20 mm. a horizontal con- 
 striction begins to divide the atrium into an upper utricular portion, into which 
 the semicircular canals open, and a lower saccular portion (Fig. 512, /, m). 
 The constriction begins on the side opposite the endolymphatic appendage and 
 gradually extends across the atrium until it finally divides the opening of the 
 endolymphatic appendage into two parts (Fig. 513, a, b, c). One of these 
 parts opens into the utricle, the other into the saccule, the two parts together 
 constituting the utriculo saccular duct. 
 
 As stated before-,- the two- or three-layered epithelium of the earlier stages 
 becomes reduced to a single layer. The cells of this layer are low cuboidal, 
 with the exception of those over small areas in the ampullae, in the saccule, and 
 in the utricle. Over an elongated area in each ampulla (crista ampullaris), a 
 round area in the saccule and another in the utricle (macula acustica), the 
 epithelium becomes high columnar, some of the cells developing cilia on their 
 free borders ("hair cells," neuro-epithelium) , the others becoming the susten- 
 tacular cells. These areas are the end-organs of the vestibular nerve (see p. 499) . 
 
 As already mentioned, the cochlear pouch appears as an outgrowth from the 
 lower side of the atrium (see also Fig. 512, b-f) . The pouch becomes somewhat 
 flattened, and, as it continues to grow in length, becomes coiled like a snail- 
 shell (Fig. 512, g-n; Fig. 513, a-c). This first formed coiled structure is the 
 cochlear duct, or scala media. At the same time, it becomes distinctly marked 
 off from the lower part of the atrium (now the saccule) by a constriction, the 
 constricted portion forming the ductus reuniens (Fig. 512, l-n; Fig 513, a-c). 
 
 All the structures thus far considered are at first closely invested by meso- 
 derm. Later, this portion of the mesoderm gives rise to special tissues, and, in 
 the region of the cochlear duct, to the scala vestibuli and scala tympani. The 
 cells immediately around the vesicle proliferate and a dense fibrous layer is 
 formed; outside of this fibrous layer the tissue becomes gelatinous; outside of 
 this again another fibrous layer is formed, around which cartilage develops. 
 The inner fibrous layer gives rise to the connective tissue that supports the 
 epithelial lining of the vesicle. The gelatinous layer degenerates to form a 
 fluid known as the peritymfb, the space containing the fluid being the perilymph- 
 atic space. The outer fibrous layer becomes the perichondrium later the 
 periosteum when the cartilage is replaced by the petrous portion of the tem- 
 poral bone. 
 
 In the cochlear region the conditions are somewhat modified. Here the 
 gelatinous layer does not form a complete covering for the cochlear duct, but is 
 interrupted along two lines, (i) Laterally the fibrous layer lying next the 
 cochlear duct is fused with the perichondrium (outer fibrous layer) (Fig. 514). 
 
THE ORGANS OF SPECIAL SENSE. 
 
 587 
 
 (2) Medially the inner fibrous layer is fused with the perichondrium of a shelf-like 
 process of cartilage which later ossifies to form the bony spiral lamina (Fig. 
 514). By these two partitions, the cochlear perilymphatic space is separated 
 into two spiral compartments which communicate only at the apex of the 
 cochlea. The larger of these compartments, the scala vestibuli, communicates 
 with the perilymphatic space around the utricle and saccule. The wall separat- 
 ing the scala vestibuli and cochlear duct becomes thinned out to form the 
 
 Cochlear duct 
 
 Cartilage 
 
 Scala vestibuli 
 (gelatinous tissue) 
 
 Cochlear duct 
 
 Cochlear (spiral) ganglion 
 
 Coch. nerve to organ of Corti 
 
 Scala tympani 
 
 Cochlear nerve 
 
 Fibrous con. tis. 
 
 Connective tissue _| 
 
 Scala vestibuli 
 Perichondrium 
 
 Vestibular membrane I| 
 Lat. wall of coch. duct fe? 
 
 Organ of Corti _ ' f 
 
 Scala tympani j 
 
 Cartilage 
 
 FIG. 514 Section through the developing cochlea of a 90 mm. cat embryo. Bottcher. 
 
 vestibidar membrane (of Reissner). The smaller compartment, the scala 
 tympani, remains separated from the cavity of the middle ear by a thin mem- 
 brane which closes the fenestra cochlea (rotunda). In the wall between the 
 scala tympani and the cochlear duct the organ of Corti develops (see below). 
 A membrane, similar to that closing the fenestra cochleae, occurs between the 
 cavity of the middle ear and the utricle, closing the fenestra vestibuli (ovalis) . 
 As alluded to above, the organ of Corti develops from the wall of the cochlear 
 
588 TEXT-BOOK OF EMBRYOLOGY. 
 
 * 
 
 duct between the latter and the scala tympani (Fig. 514). The epithelial cells 
 of the cochlear duct in this region become high columnar and arranged in two 
 ridges which extend throughout the entire length of the duct. The cells of the 
 ridge nearer the axis of the cochlea give rise to the membrana tectoria. Whether 
 this is accomplished by cuticular secretion of the cells or by the fusion of long 
 hair-like processes that grow from their free borders is not known. The cells of 
 the outer ridge become differentiated into four groups. Those of the outer 
 group (next the cells that give rise to the membrana tectoria) develop into the 
 inner hair cells; those of the next group form the pillar cells; those of the third 
 group differentiate into the outer hair cells; and those of the fourth (outer) 
 group give rise to Hensen's cells. The hair cells, as the name indicates, develop 
 delicate hair-like processes on their free borders, and, since the peripheral 
 processes of the spiral (cochlear) ganglion cells end around them, are con- 
 sidered as the sensory cells of the cochlea, or auditory receptors (see p. 499). 
 
 THE ACOUSTIC NERVE. The acoustic ganglionic mass is at first closely 
 associated with the geniculate ganglion (ganglion of the facial (VII) nerve) , the 
 two together often being spoken of as the acustico-facialis ganglion (see also 
 p. 508). This lies in close contact with the anterior wall of the auditory vesicle 
 when the latter is first constricted from the ectoderm. The origin of the gang- 
 lion has not been traced in Mammals, but in cow embryos the geniculate has 
 been seen to be connected with the ectoderm at the dorsal end of the first 
 branchial groove (Froriep). The acoustic ganglion probably belongs to the 
 lateral line system (Kupffer) (see also p. 460). 
 
 Although the geniculate and acoustic ganglia are at first closely associated, 
 each pursues an independent course of development. The description here 
 will be confined to the acoustic. As already mentioned, this lies in close apposi- 
 tion to the side of the neural tube and the auditory vesicle and just anterior to 
 the latter (Fig. 512, a). At a very early stage (embryos of 6-7 mm.), the mass 
 shows a differentiation into two parts a dorsal one, the future vestibular 
 ganglion, and a ventral one, the future cochlear (spiral) ganglion (Fig. 512, b, c). 
 The ganglion cells become bipolar (see p. 499), and, as is peculiar to the cells of 
 the acoustic ganglia, remain in this condition. One process of each cell grows 
 centrally to form a root fiber of the acoustic nerve, which terminates in contact 
 with dendrites of neurones in certain nuclei in the central nervous system. The 
 fibers from the cells of the vestibular ganglion form the vestibular root, those 
 from the cells of the cochlear ganglion form the cochlear root. The other proc- 
 ess grows peripherally and penetrates the wall of the auditory vesicle to enter 
 into relation with certain cells that differentiate from the epithelial lining of the 
 vesicle. 
 
 The peripheral processes of the vestibular ganglion cells come into relation 
 with specialized cells (hair cells) in the ampullae of the semicircular canals 
 
THE ORGANS OF SPECIAL SENSE. 589 
 
 (crista ampullaris) and in the saccule and utricle (macula acustica) (see 
 p. 586) . The nerve itself becomes divided into certain branches, as indicated 
 in the following table (Streeter}. The peripheral terminations of the various 
 branches are indicated in parentheses. Compare with Fig. 512, /, m, n, and 
 Fig. 513, a, b, c. 
 
 ramus ampul, sup. (crista ampul.) 
 
 pars superior 
 
 ramus ampul, ext. (crista ampul.) 
 
 ramus recess, utric. (macula acust.) 
 N. vestibularis ] 
 
 J ramus saccul. (macula acust.) 
 [ pars inferior | ramus ampul, (crista ampul.) 
 
 The vestibular ganglion cells, instead of remaining in a compact mass, come 
 to form two fairly distinct masses in the course of the nerve (Fig. 513, 0, b, c). 
 One of these apparently is connected with the pars inferior, the other with the 
 pars superior. 
 
 The cochlear ganglion cells at an early stage become closely associated with 
 the developing cochlear duct and, as the latter forms a spiral, are carried" along 
 with it. They thus come to form an elongated group of cells extending through- 
 out the entire length of the cochlea (whence the name, spiral ganglion) (Fig. 
 512, j-n; Fig. 513, a-c). Consequently, the peripheral processes of these cells, 
 which terminate in connection with the hair cells of the organ of Corti, are com- 
 paratively short. The central processes are naturally longer and form the 
 cochlear nerve root which is twisted like a rope in part of its course (Fig. 513, c). 
 
 The Middle Ear. The cavity of the middle ear develops from the upper 
 (dorsal) part of the first inner branchial groove. The epithelial lining of the 
 cavity is thus of course derived from entoderm, and the other structures 
 (auditory ossicles, etc.) from the adjacent mesoderm. 
 
 It has been stated elsewhere that the mesoderm in the first and second 
 branchial arches gives rise, among other things, to certain skeletal elements. 
 In the first arch there develops a rod of cartilage, known as Meckel's cartilage, 
 which extends from the symphysis of the lower jaws to the region of the upper 
 part of the first inner branchial groove (p. 196; Figs. 174, 177, 180). The 
 proximal end of the cartilage becomes constricted to form two masses which 
 constitute the anlagen of the malleus and incus (Figs. 173 and 174). In the 
 second arch there develops a rod of cartilage which forms the lesser horn of the 
 hyoid bone, the stylohyoid ligament, and the styloid process (Figs. 174, 177, 
 1 80) . In close relation to the dorsal end of the styloid process, in the mesoderm 
 destined to give rise to the periotic capsule, a mass of cartilage appears which 
 is destined to give rise to the stapes (except the base ?) . It has not been fully 
 determined whether the stapes is actually a derivative of the cartilage of the 
 second arch or of the mesenchyme near its dorsal end. It has been suggested 
 
590 TEXT-BOOK OF EMBRYOLOGY. 
 
 that the base of the stapes is of intramembranous origin and that the rest of the 
 bone is derived from the cartilage of the second arch. Its close association 
 with the cartilage of the second arch possibly indicates its phylogenetic origin 
 from the latter. 
 
 At first the auditory ossicles are embedded in the mesoderm dorsal to the 
 first inner branchial groove, that is, dorsal to the cavity of the middle ear. As 
 development proceeds, the mesoderm is converted into a spongy tissue which 
 finally degenerates. At the same time the ear cavity enlarges and wraps itself, 
 as it were, around the ossicles. The latter thus come to lie within the cavity 
 of the tympanum, but are covered by a layer of epithelium (entoderm) which 
 is continuous with that lining the cavity. 
 
 Toward the end of fcetal life, outgrowths from the cavity of the tympanum 
 begin to invade the temporal bone. This process continues for some time 
 after birth and results in the formation of cavities within the mastoid part of 
 the temporal bone. These cavities are the mastoid cells, the epithelial lining 
 of which is continuous with that of the tympanic cavity. 
 
 The Eustachian tube represents the lower (ventral) portion of the diver- 
 ticulum which forms the cavity of the tympanum. In other w r ords, as the 
 dorsal part of the first inner branchial groove enlarges to form the cavity of the 
 middle ear, the narrow part of the groove, just ventral to the cavity, persists 
 as a communication between the latter and the pharynx. 
 
 The Outer Ear. The outer ear is formed from the dorsal part of the first 
 outer branchial groove and the adjacent portions of the first and second arches 
 (see Fig. 123). The ventral part of the groove flattens out and disappears. 
 The dorsal part becomes deeper to form a funnel-shaped depression (during 
 the second month; Fig. 126). From the deeper part of the funnel a solid mass 
 of ectoderm grows inward until it comes into relation with the mesoderm im- 
 mediately around the developing cavity of the tympanum, or, more specifically, 
 the mesoderm surrounding the handle of the malleus. Here it spreads out 
 into a disk-like mass. About the seventh month, the disk splits into two layers. 
 The inner layer, which is separated from the epithelium of the middle ear by a 
 thin sheet of mesoderm, becomes the outer layer of the tympanum. The 
 tympanum is thus composed of an inner (entodermal) and an outer (ectoder- 
 mal) layer, with a small amount of mesoderm between. From its mode of 
 development, the tympanum may be considered in a sense as the wall which 
 separates the first inner from the first outer branchial groove. 
 
 The split in the ectodermal disk (see above) gradually extends outward, 
 invading the solid ectodermal invagination until it finally unites with the 
 bottom of the funnel-shaped depression on the surface, thus forming the 
 external auditory meatus. 
 
 The external ear for auricle) is derived from the portions of the first and 
 
THE ORGANS OF SPECIAL SENSE. 
 
 591 
 
 second branchial arches surrounding the dorsal part of the first outer branchial 
 groove (see Figs, 122, 123, 126, 127). About the end of the fourth week, the 
 caudal border of the first arch exhibits three small elevations or tubercles 
 (Fig. 515, A, 1-3), the cranial border of the second arch the same number (Fig. 
 515, A, 4-6). A groove, extending down the middle of the second arch, marks 
 off a ridge (c) lying caudal to the three tubercles. The ventral tubercle (i) of 
 the first arch gives rise to the tragus. The middle tubercle (5) of the second arch 
 
 \ 
 
 
 _r 
 
 FIG. 515. Stages in the development of the external ear (auricle). A, Embryo of n mm.; B y of 
 13.6 mm.; C, of 15 mm.; D, foetus at the beginning of the 3d month; E, foetus of 8.5 cm.; 
 F, fcetus at term. For explanation of numerals, see text. His, McMurrich. 
 
 develops into the antitragus. The middle and dorsal tubercles (2 and 3) of 
 the first arch unite with the ridge (c) on the second arch to form the helix. 
 The dorsal tubercle (4) of the second arch gives rise to theanthelix. The 
 ventral tubercle (6) of the second arch produces the lobule. It should be noted 
 that in the third month the dorsal and caudal portions of the helix are bent 
 forward and conceal the anthelix. 
 
 Anomalies. 
 
 Malformations of the nose have been alluded to in connection with hare lip, 
 cleft palate, etc., on page 212, and are also discussed in the chapter on tera- 
 togenesis (XIX) . Malformations affecting the eye (cyclopia, microphthalmia, 
 etc.) and the ear (synotia, etc.) are dealt with in the chapter on teratogenesis. 
 
592 TEXT-BOOK OF EMBRYOLOGY. 
 
 References for Further Study. 
 THE EYE. 
 
 GALLENGA: Entwickelung des Auges. Encyklopddie der Augenheilkunde, Lief. 6 and 7, 
 1902. 
 
 HOLDEN: An Outline of the Embryology of the Eye, New York, 1893. 
 
 VON KOLLIKER: Die Entwicklung und Bedeutung des Glaskorpers. Zeitschr. fur 
 wissensch. Zoolog., Bd. LXVI, 1904. 
 
 LANGE, O.: Einblicke in die embryonale Anatomic und Entwicklung des Menschen- 
 auges. 1908. 
 
 RABL, C.: Ueber den Bau und Entwickelung der Linse. Zeitschr. fur wissensch. ZooL, 
 Bd. LXII and LXV, 1898; LXVII, 1899. 
 
 RAYMON Y CAJAL.: Nouvelles contributions a 1'etude histologique de la re'tine. Jour, de 
 VAnat. et de la PhysioL, Vol. XXXII, 1896. 
 
 ROBINSON. A.: On the Formation and Structure of the Optic Nerve and its Relation to 
 the Optic Stalk. Jour, of Anat. and Physiol., Vol. XXX, 1896. 
 
 VON SPEE: Recherches sur Porigine du corps vitre. Arch, de Biol., Vol. XIX, 1902. 
 
 THE NOSE. 
 
 BEARD, J.: Morphological Studies. The Nose and Jacobson's Organ. Zool. Jahrbuch, 
 Bd. Ill, 1889. 
 
 DISSE, J.: Die erste Entwickelung der Riechnerven. Anat. Hefte, Bd. IX, 1897. 
 
 His, W.: Beobachtungen zur Geschichte der Nasen- und Gaumenbildung beim 
 menschlichen Embryo. AbhandL d. math.-phys. Klasse Ko'nig. Sachs. Gesellsch. d. 
 Wissensch., 1901. 
 
 HOCHSTETTER, F.. Ueber die Bildung der primitiven Choanen beim Menschen. Ver' 
 handl. d. anat. Gesellsch., Bd. VI, 1892. 
 
 VON MIHALKOWICZ, V.: Nasenhohle und Jacobsonsches Organ. Eine morphologische 
 Studie. Anat. Hefte, Bd. XI, 1898. 
 
 PETER, K.: Die Entwickelung des Geruchsorgans und Jacobson'schen Organs in der 
 Reihe der Wirbeltiere. In Hertwig's Handbuch d. vergleich. u. experiment. Entwickel- 
 ungslehre d. Wirbeltiere, Bd. II, Teil II, 1901. 
 
 THE EAR. 
 
 BAGINSKY, B.: Zur Entwickelung der Gehorschnecke. Arch.f. mik. Anat., Bd. XXVIII, 
 1886. 
 
 BOETTCHER, A.: Ueber Entwickelung und Bau des Gehorlabyrinths. Verhandl. d. 
 Kais.Leop. -Carol. Akad., Bd. XXXV, 1869. 
 
 BROMAN, I.: Die Entwickelungsgeschichte der Gehorknochelchen beim Menschen. 
 Anat. Hefte, Bd. XI, 1898. 
 
 FUCHS, H.: Bemerkungen iiber die Herkunft und Entwickelung der Gehorknochelchen 
 bei Kaninchen-Embryonen. Arch.f. Anat. u. Phys., Anat. Abth., SuppL, 1905. 
 
 HENSEN, V.: Zur Morphologic der Schnecke. Zeitschr. f. wissensch. ZooL, Bd. XIII, 1863 
 
 His, W.: Zur Entwickelung des Acusticofacialisgebiets beim Menschen. Arch.f. Anat. 
 u. Phys., Anat. Abth., SuppL, 1899. 
 
 KRAUSE, R.: Entwickelungsgeschichte des Gehororgans. In Hertwig's Handbuch d. 
 vergleich. u. experiment. Entwickelungslehre d. Wirbeltiere, Bd. II, Teil II, 1902. 
 
 STREETER, G. L.: On the Development of the Membranous Labyrinth and the Acoustic 
 and Facial Nerves in the Human Embryo. Am. Jour, of Anat., Vol. VI, No. 2, 1907. 
 
CHAPTER XIX. 
 
 TERATOGENESIS. 
 
 MALFORMATIONS INVOLVING MORE THAN ONE INDIVIDUAL. 
 Classification, Description, Origin. 
 
 To give a complete list of the numerous malformations in man, even of 
 those which affect the external form of the body, is obviously beyond the scope 
 of this book. In this chapter it is the purpose of the writers merely to describe 
 in a general way the most striking malformations and discuss briefly the causes 
 underlying the origin of malformations. For further details concerning the 
 subject the student's attention is directed to "References for Further Study" 
 
 The classification of malformations is attended by great difficulties. This 
 is due mainly to the fact that their complexities are not wholly understood. It 
 is due also in a measure to the fact that, apart from certain malformations 
 which always occur in like manner in different individuals, there are so many 
 irregularities and deviations from any type that might arbitrarily be chosen. 
 The classification made by St. Hilaire three-quarters of a century ago, 
 although apparently complete, showed many incongruities as teratology 
 became more firmly established upon an embryological basis. Later 
 Bischoff formulated a division based upon the embryological significance 
 of malformations. This in turn was elaborated by Forster, and Forster's 
 scheme has been adopted by Marchand and others. As knowledge concern- 
 ing teratogenesis is added to, it may be that further changes in classification will 
 be necessary, especially in view of the fact that much light is being thrown by 
 experimental methods upon the origin of malformations. 
 
 Marchand's scheme of duplicate monsters is given here as a convenient one 
 for a comprehensive view of anomalous conditions affecting two individuals. 
 I. Both bodies derived from anlagen which developed from one ovum 
 and which were originally similar and symmetrical: Symmetrical 
 duplicity. 
 A. Both bodies originally complete : Complete duplicity. 
 
 i. The two bodies remain separate; union confined to chorion: 
 Twins; free duplicities. 
 
 a. Both bodies formed alike, each capable of living: Equal 
 monochorionic twins. 
 593 
 
594 TEXT-BOOK OF EMBRYOLOGY. 
 
 b. One body normal, the other abnormal or much mal- 
 formed: Unequal monochorionic twins. 
 
 2. The two bodies united; formed alike (equal), or one remains 
 more or less rudimentary (unequal) : Twins joined together; 
 duplicate monsters. 
 
 a. Union confined to lower end of body: Double monsters 
 with posterior union; anterior duplicity. 
 
 b. Union confined to middle of body, or extending from 
 middle forward: Double monsters with middle union. 
 
 c. Union limited to upper end of body, or extending from 
 upper end downward: Double monsters with anterior 
 union; posterior duplicity. 
 
 B. Duplicity does not affect entire anlage, but only a part : Incomplete 
 duplicity. 
 
 1. Two incomplete anlagen (or primitive streaks) pass over into 
 a single anlage: Posterior incomplete duplicity. 
 
 2. An originally single anlage forms by dichotomous growth two 
 separate upper (anterior) ends: Anterior incomplete duplicity. 
 
 In addition: Triplicity, quadruplicity, etc., (multiplicity). 
 II. Both bodies derived from two originally dissimilar, asymmetrical 
 anlagen, of which one, always rudimentary, becomes more or less en- 
 closed and nourished by the other: True parasitic duplicity; asym- 
 metrical duplicity. 
 
 In addition: Teratoid tumors. 
 
 SYMMETRICAL DUPLICITY. 
 
 As seen from the foregoing scheme, there are included under this head 
 double forms in which both embryos develop within a single chorion (mono- 
 chorionic twins), and in which the bodies may be distinct and separate 
 (complete duplicity) or may be united (incomplete duplicity). In complete 
 duplicity each embryo usually possesses its own amnion and umbilical cord, 
 but both are attached to the same placenta. In such cases the conditions of 
 nutrition and rate of growth may be so similar in the two individuals that their 
 development is equal (equal monochorionic twins). They may grow to 
 maturity, and they always bear a remarkable resemblance to each other in 
 physical features and in mental characteristics and are always of the same 
 sex. More commonly, however, the development of separate monochorionic 
 twins is unequal, caused probably by dissimilar conditions of nutrition. In 
 some instances the less favored individual is but slightly affected, so that it 
 may be born and be able to maintain an independent existence. On the other 
 
TERATOGENESIS. 595 
 
 hand, the nutrition of one embryo may be so seriously impaired that it dies. 
 When death occurs during the earlier months of pregnancy the dead embryo 
 is subjected to pressure by the living one and is sometimes distorted and 
 flattened into a thin mass known as a fcetus papyraceus. 
 
 Equal growth of monochorionic twins implies an almost perfect nutritive 
 balance, since both embryos derive their nourishment from the same placenta. 
 Any condition that disturbs the nutritive balance tends to affect adversely the 
 less favored embryo, so that development does not proceed equally (unequal 
 monochorionic twins). One of the first consequences of such a disturbance 
 may be an impaired or arrested development of the heart, in which case the 
 weaker embryo may become an acardiac monster. 
 
 This condition does not necessarily imply the absence of the heart in the 
 affected twin; for it may possess a functionating heart, or it may become an 
 amorphous mass of tissue which derives its total blood supply through the 
 action of the heart of the stronger twin, or there may be any form between the 
 two extremes. In any case the acardiac monster acardiacus receives its 
 blood wholly or in part through the agency of the stronger heart. 
 
 Acardia is always accompanied by a so-called "reversal of the circulation;" 
 and there are three periods at which it may originate, (i) It may originate 
 before the heart develops. As is well known, the heart appears independently 
 of the area vasculosa and joins the vessels secondarily (p. 222). If, for any 
 reason, the heart of one of the embryos fails to develop, anastomoses may 
 occur between the vascular anlagen of the two vascular areas and consequently 
 the normal embryo assumes the duty of nourishing the other. The latter be- 
 comes an acardiac monster. (2) It may originate after the heart has begun to 
 develop, but before the placental circulation is established. If, for any reason, 
 the heart of one embryo should cease to develop further, there would probably 
 be sufficient anastomoses between the vitelline vessels of the two embryos to 
 enable the affected embryo to live and become an acardiac parasite. In this 
 case no placental circulation would develop in the parasite. (3) Acardia may 
 originate after the establishment of the placental circulation. Since there is 
 but one chorion or placenta for both embryos there is naturally a communica- 
 tion between the two circulations in the chorionic villi. There are also likely 
 to be anastomoses between the umbilical arteries and veins. If, for any reason, 
 the heart action of one of the embryos should become impaired, there would be 
 an influx of blood into the vessels of that embryo owing to diminished pressure. 
 Thus the blood from the stronger heart would be pumped into the affected 
 embryo as well as into the placenta. This blood, being impure, fails to nourish 
 the weaker embryo properly and the result is atrophy or degeneration. 
 
 Upon the basis of other malformations that naturally accompany impaired 
 development of the heart, acardiac monsters are divided into four classes. 
 
596 TEXT-BOOK OF EMBRYOLOGY. 
 
 i. Acardiacicompleti. The general development of the acardiacus depends upon 
 the sufficiency of the blood supply which it receives. If there is a well developed 
 anastomosis between the two placental circulations the weaker embryo may 
 receive a moderately good blood supply and develop into a fairly normal foetus. 
 A well formed trunk and head may be present and the extremities may be 
 represented in part or in full. 2. Acardiaci acormi. These may possess only a 
 head, or they may possess a head and traces of a trunk and extremities. 
 Their evolution depends upon unusual combinations of anastomoses in their 
 venous channels. 3. Acardiaci acephali. No head is present. The lower 
 part of the trunk is present, and sometimes other parts of the trunk. The ex- 
 tremities may be complete, incomplete or absent. These forms are also due 
 to peculiar combinations of vascular anastomoses. 4. Acardiaci amor phi. As 
 the name indicates, there is no typical form for the affected embryo. It bears no 
 resemblance to a normal embryo, but is merely an irregular mass of tissue. 
 
 In symmetrical duplicity, instead of the two embryos in one chorion being 
 distinct and separate individuals, they may be joined together to a greater or 
 lesser extent. The two individuals may develop to practically the same 
 degree (equal united twins,) or one may remain more or less rudimentary 
 (unequal united twins.) As may be seen by reference to the scheme on page 605, 
 there are three modes of union posterior, middle and anterior. 
 
 Posterior Union. This may be either dorsal or ventral. In dorsal posterior 
 union the two bodies are joined together in the pelvic region, with the dorsal 
 surfaces of the twins directed toward each other. The umbilicus is double and 
 the two umbilical cords converge toward a common placenta pygopagus. 
 The general anatomical features are as follows. There is a single coccyx 
 and a single sacrum; pelvic bones and symphyses are present in normal 
 number; near the ends of the large intestines the two digestive tubes unite to 
 form a common lumen, and the two recta open through a common anus between 
 the more dorsally situated pair of extremities; the two spinal cords unite near 
 their lower ends to form a single conus and filum terminale; the urogenital 
 tracts are united only to a slight degree. This form of monster is of interest 
 because it is able to live for years; indeed a number of them have lived to 
 maturity. 
 
 In case of ventral posterior union the attachment may be confined to the 
 pelvic region or may involve the entire trunk. In the former instance 
 ischiopagus the right pubic bone of one pelvis fuses with the left pubic bone 
 of the other pelvis, the ventral surfaces of the two sacra facing each other. 
 The axes of the bodies may be in line, or they may form an angle. The con- 
 tinuous ventral surfaces of the two bodies contain a single umbilicus. The 
 organs in the pelvic region may be single or double. The lower extremities 
 may be fully developed, or there may be only three, or rarely two. Sometimes 
 
TERATOGENESIS. 597 
 
 one of the twins is rudimentary, the thorax and head being absent, but the 
 extremities present in part (ischiopagus parasiticus) . Ischiopagi seldom 
 survive owing to atresia of the anus. 
 
 In case the attachment extends along the entire trunk of each twin 
 ischiothoracopagus the two sacra are usually fused to form a single sacrum. 
 The thoraces of the twins are joined by means of a common sternum. The 
 upper extremities may all be present (tetrabrachius), or there may be three 
 (tribrachius), or only two (dibrachius) and a very rudimentary third. The 
 lower extremities are subject to the same variations as the upper. The ex- 
 ternal genitalia and anus are single. The alimentary tube is double as far as 
 the lower end. The thoracic viscera are partly double. Monsters of this 
 type may live for years. 
 
 Middle Union. In the case of middle union a ventral or ventro-lateral 
 attachment extends from the umbilicus for a variable distance toward the head. 
 In most cases the umbilicus itself is single. The union may occur in the 
 region of the xiphoid process xiphopagus or it may involve the entire region 
 of the sternum sternopagus or thoracopagus. In the case of xiphopagus, 
 a bridge joining the twins extends from the common umbilicus to the 
 xiphoid processes. The latter are usually united across the bridge. The 
 thoracic cavities are separate. The two livers may be connected by a bridge of 
 hepatic tissue, in which case the two peritoneal cavities are in communication, 
 or the livers may remain separate, in which case the peritoneal cavities do not 
 communicate. The two alimentary tubes may or may not communicate in the 
 region of the stomach. Xiphopagi may live for many years, as instanced by 
 the "Siamese Twins." 
 
 In the case of sternopagus the union extends upward from the common um- 
 bilicus, so that the two sterna are fused into a single bone. There is a com- 
 mon thoracic cavity, separated from the abdominal cavity by a single diaphragm. 
 One or two hearts may be present. The middle portions of the two alimentary 
 tubes form a single tract. The two livers are fused into a common mass. The 
 genitalia are distinct and separate. The extremities may be normal, or in case 
 of a ventro-lateral union, the approximated upper extremities may be fused. 
 Such monsters are usually born dead; if born alive, they survive but a short 
 time owing to defective development of the heart. 
 
 As other varieties of thoracopagus the following may be mentioned : Thora- 
 copagus parasiticus, in which one twin is much arrested in development, a head 
 and heart being present, and attached to the thoracic region of the stronger 
 twin. Gastrothoracopagus dipygus (dipygus parasiticus), in which extremities 
 and trunk are present at least in part and are attached to the lower part of the 
 thorax or to the epigastrium of the other twin. The head is not present. Such 
 twins may live for years, as instanced by Laloo. Cephalothoracopagus diproso- 
 
598 TEXT-BOOK OF EMBRYOLOGY. 
 
 fus } in which the attachment may extend into the neck and head region, so 
 that there is a union from the head to the umbilicus. This type is distinguished 
 from the anterior union in that the head portions of the twins are united 
 laterally, so that both more or less completely developed faces are turned 
 toward the common ventral side, while the bodies have their ventral sides 
 directed toward each other. 
 
 Anterior Union. In this type of union the attachment may be dorsal and 
 confined to the head (dorsal anterior union), or ventral and reaching as far as 
 the umbilicus (ventral anterior union). 
 
 In dorsal union the heads of the twins are joined at the crowns, so that 
 the two bodies lie in a straight line, or form an angle with each other. Such 
 a monstrosity is known as craniopagus (cephalopagus) . The attachment 
 usually involves the cranial vault, the two brains remaining separated by 
 their membranes within a common cranial cavity. Such monsters are rare 
 and survive but a short time. A very rare variety of craniopagus is the 
 form known as craniopagus parasiticus, in which one twin is reduced to a 
 rudimentary structure and is parasitic upon the other. In all the above cases 
 the term autosite is applied to the better developed twin. 
 
 In ventral and ventro-lateral union the attachment involves the head, 
 neck and thorax syncephalus, cephalothoracopagus janiceps. The twins pass 
 through their development in common, each individual contributing its 
 quota of structure to the composite monster. The sternum is single, the oeso- 
 phagus single, the larynx and trachea double or single, the stomach single, the 
 intestine double. The two hearts may be united, but more commonly are 
 separated, one being situated ventrally, the other dorsally. Two faces are 
 formed, one belonging to each embryo. The faces may be alike or nearly so 
 (Janus symmetros), or one may be misplaced or unequally developed (Janus 
 asymmetros), which often results in cyclopia, synotia, or obliteration of the 
 opening of the mouth. 
 
 In some cases the greater part of the body is single and only a part is double 
 (incomplete duplicity). The malformation may affect only the upper end or 
 head (superior incomplete duplicity), or only the lower end (inferior incomplete 
 duplicity). In the former case the skull is single, with possible traces of a 
 double formation diprosopus. There are two faces with varying degrees of 
 fusion between them; all four eyes may be present, or the two approximated 
 eyes may be fused or they may be wanting (diprosopus tetroph-, trioph-, 
 diophthalmus). The two mouths may be fused (diprosopus monostomus), 
 and with a greater degree of fusion between the faces the two approximated 
 ears may also be fused or be entirely lacking. In dicephalus the head is 
 double, and sometimes the upper end of the vertebral column. 
 
 Inferior incomplete duplicity is rare. To this category of duplicate monsters 
 
TERATOGENESIS. 599 
 
 probably belong certain cases of partial duplicity in the pelvic region, with 
 sometimes an extra set of genitalia. Possibly also a few cases of a third lower 
 extremity would come under this head. 
 
 Multiplicity. Monochorionic triplets are rare, only a few cases being 
 recorded. Two cases of monochorionic quadruplets are on record, and 
 one case of quintuplets. Incomplete multiplicities are extremely rare. One 
 case of incomplete triplicity has been described tricephalus. Two verte- 
 bral columns were present in this monster, bearing one and two heads re- 
 spectively. Two thoracic cavities, each enclosing a heart, were separated by 
 a thin septum. The abdominal viscera were single. The lower half of the 
 body and the lower extremities were normal, as were also the genital organs, 
 which were male. 
 
 ORIGIN OF SYMMETRICAL DUPLICITY. 
 
 The origin of duplicities has always been most difficult to explain, and 
 the many solutions suggested have been replete with conjecture. The diffi- 
 culty has been caused by the lack of direct observation upon formative stages 
 either in the lower or higher animals. Within recent years, however, experi- 
 mental work upon the lower forms has begun to throw some light upon this 
 obscure problem. Among the theories which have been formulated are two 
 that stand out most clearly the fusion theory (Marchand, Ziegler) and the 
 fission theory (Ahlfeld and others). 
 
 According to the fusion theory, there are present two originally distinct 
 anlagen within a single ovum. These two anlagen may develop separately and 
 independently and produce twins. They may come in contact during develop- 
 ment and fuse to a greater or lesser degree, thus producing some kind of dupli- 
 cate monster. If fusion does occur it occurs between similar parts of the two 
 anlagen; in other words, like tissues and organs fuse liver with liver, muscle 
 with muscle, bone with bone, and so on. Such unions, however, probably 
 occur only in very early stages of development, for when tissues are once formed, 
 union is effected with much greater difficulty. Consequently fusions between 
 two anlagen, leading to double monsters, probably take place at a very early 
 period of intrauterine life. 
 
 According to the fission theory, duplicity is the result of the division of a 
 single anlage in the earliest stages of development, before the formation of the 
 primitive streak. The cleavage is produced by mechanical resistance of the 
 zona pellucida. Since the greatest mass of growing material is in the head 
 region, the resistance is greatest there, and hence it is argued that duplicities 
 would be most common in the head region, which accords with the facts. A 
 modification of the fission theory to explain duplicities which affect a relatively 
 small area has been suggested. Incomplete anterior duplicity, for example, is 
 
600 TEXT-BOOK OF EMBRYOLOGY. 
 
 not the result of fission but of bifurcation which accompanies the development 
 of the head end of the embryo along divergent axes. The difference between 
 fission and bifurcation is that the former is the passive result of active 
 mechanical forces, while the latter is a part of active formative processes. 
 
 Experiments on eggs of lower animals point to the conclusion that each of 
 the two blastomeres resulting from the first cleavage contains the material 
 necessary to produce an entire body. In order to cause a blastomere to pro- 
 duce a whole body, however, it is necessary to subject it to unnatural conditions. 
 For example, if one of the two primary blastomeres of the frog is killed and the 
 other left to grow in its natural position it will produce a half-embryo; but if the 
 remaining blastomere is inverted it will produce a whole embryo (Morgan). 
 On the other hand, in view of certain experiments on the eggs of Amphioxus, 
 it has been asserted that duplicity is associated with double gastrulation; 
 when these eggs were shaken during the first cleavage, some developed into 
 double gastrulae (Wilson, Hertwig). For a further discussion of these causes, 
 see page 624. 
 
 ASYMMETRICAL DUPLICITY. 
 
 In this type of malformation the two anlagen from which the monster is 
 derived are primarily dissimilar and unequal. One anlage usually remains in 
 a rudimentary condition, bears little or no resemblance to a foetus, and 
 becomes a parasite upon or within the body derived from the other anlage 
 (parasite, foetal inclusion, foetus in fcetu). Sometimes, however, the dependent 
 embryo may develop quite complete parts, such as extremities, but always 
 remains attached to the stronger embryo, from which it derives its nourishment 
 (implantation). Parasitic inclusions and implantations may be attached to 
 the autosite in the region of the head, neck, thorax, abdomen, etc. 
 
 Parasitic duplicities in the head region may take the form of masses pro- 
 truding from the orbital region prosopopagus parasiticus or much more com- 
 monly from the mouth epignathus, sphenopagus. In the latter case the tumor 
 is enveloped by skin containing hair follicles and sweat glands, and usually 
 consists of cysts and intervening embryonic tissue. It sometimes contains teeth, 
 cartilage, bone, fat and nerve tissue, even traces of an intestinal canal and 
 of liver tissue. One epignathus has been described as having an imperfect 
 set of female genitalia which lay between two rudimentary lower extremities. 
 
 Occasionally irregular tumors are found in the region of the pituitary body 
 (encranius), which contain rudiments of various tissues and organs. In such 
 cases the parasitic anlage has possibly been included during the imagination 
 which forms the oral part of the pituitary body. Tumors consisting of various 
 tissues, such as lymphatic, adipose, muscle, etc., are also found in the brain 
 
TERATOGENESIS. 601 
 
 ventricles. They possibly represent parasitic anlagen which have become en- 
 closed within the brain vesicles as the neural groove closed in dorsally. 
 
 Certain foetal inclusions attached to the region formed by the branchial 
 arches are spoken of as cervical parasites. These are usually cystic tu- 
 mors, covered with skin and containing teeth, bone and parts of a head and 
 extremities. 
 
 Closely associated with the cervical parasites is a group of tumors found 
 within the anterior mediastinum in the region of the thymus gland, and known 
 as thoracic parasites. It must be borne in mind, however, that some of the 
 tumors found in the cervical and thoracic regions are not true parasitic in- 
 clusions, but are dermoid cysts (resembling the parasites) derived from the 
 ectoderm. True parasitism implies origin from all three germ layers. From 
 a structural standpoint it is sometimes very difficult, even impossible, to distin- 
 guish between true parasitic inclusions and dermoid cysts that are derived from 
 ectoderm. 
 
 Very rarely in the human subject some parasitic structure is attached to the 
 back. One case of a supernumerary penis in the lumbar region has been de- 
 scribed; another case is on record of an almost complete set of female genitalia 
 on the back of a male. Such malformations can be explained only by assum- 
 ing the partial development of another embryonic anlage. 
 
 Sacral parasites are the most frequent of the true parastic growths. These 
 are cystic tumors which are attached to and hang from the sacrum or the 
 coccyx. The tumors are covered with skin which blends with the skin of the 
 autosite. In the existence of such elements as fat, bone, muscle, and nerves, 
 and the rudiments of intestines and extremities is found the evidence of their 
 fcetal origin. 
 
 Foetal inclusions in the abdominal region are not frequent. One very rare 
 intraparietal (or subcutaneous) inclusion, in a child two and one-half years 
 old, proved to be a cystic tumor which contained a fairly well formed foetus 
 with defective head and extremities. Engastric (intraabdominal) parasites 
 are usually found in the region of the lesser peritoneal sac, at the root of the 
 transverse mesocolon. These tumors are usually enclosed within a sac of 
 mesenteric or peritoneal tissue. There may be well marked fcetal structures, 
 such as head, trunk, extremities, etc., or only traces of rudimentary organs. 
 The presence of an intraabdominal parasite does not necessarily cause the 
 death of the autosite immediately after birth; for one case in particular is on 
 record in which the autosite (a boy) lived to be fifteen -ears old with a parasite 
 that was capable of independent movement. 
 
 Parasitic Structures in the Sexual Glands. The type of tumor referred to 
 here forms a group that is of especial interest owing to their relative frequency 
 of occurrence and to their peculiar mode of production. In connection with 
 
602 TEXT-BOOK OF EMBRYOLOGY. 
 
 the ovary dermoid cysts and other solid masses occur. The cysts consist of a 
 sac enclosing hair and adipose tissue; not infrequently teeth are also present, as 
 well as sebaceous and sweat glands. Sometimes there are also bone, cartilage, 
 muscle, and nerve tissue and traces of the digestive and respiratory systems and 
 of thyreoid gland; more rarely traces of mammary glands, finger nails and 
 retinal pigment are present. In the rarer solid tumors that develop in rela- 
 tion to the ovary all three germ layers are represented, but their derivatives 
 are more rudimentary and not so regularly arranged as in the cysts. 
 
 Parasitic growths in the testis are much less frequent than in the ovary. 
 The cysts are rarer than the solid masses. These are probably homologous 
 with the parasites of the ovary. 
 
 ORIGIN OF ASYMMETRICAL (PARASITIC) DUPLICITY. 
 
 Parasitic duplicity implies primary inequality of the embryonic anlagen; in 
 other words, the anlage of the parasite is inferior, so to speak, to the anlage of 
 the host. During development the inequality or asymmetry persists or be- 
 comes more conspicuous until the parasite is more or less enclosed within the 
 autosite. As the autosite develops in a manner at least simulating the normal, 
 the parasite remains in a more or less rudimentary condition, with perhaps only 
 a few tissues which show any differentiation. In some cases the parasite 
 becomes enclosed partially or completely within the autosite (epignathus) , in 
 other cases the parasitic growth apparently occurs primarily within the autosite 
 (ovarian cysts). 
 
 The manner in which the rudimentary anlage becomes surrounded by the 
 more nearly perfect anlage is, of course, not known through direct observation. 
 But it seems reasonable to assume that such enveloping occurs in connection 
 with or as a part of the normal processes of folding by which the external form 
 of the body is established. This folding occurs at the cephalic and caudal poles 
 of the embryonic disk and also along its entire length. In addition there is 
 also the folding in of the neural groove along the dorsum of the embryo, and 
 the invagination of the branchial grooves. One can readily imagine the para- 
 sitic anlage as attached to some one of the areas that are folded in, so that 
 it is carried wholly or partially into the interior of the stronger embryonic 
 anlage and becomes surrounded by the tissues of the autosite to produce a 
 true foetal inclusion. 
 
 There seems to be little doubt as to the existence of a second, more or less 
 rudimentary anlage which becomes the parasite; in other words, there is almost 
 certainly a duplicity to begin with, although it may be an asymmetrical one. 
 It is also plausible to assume that for a time the weaker anlage develops in- 
 dependently of the stronger, but that later it is dependent upon the stronger 
 
TERATOGENESIS. 603 
 
 for its nutrition. The problem, however, is to explain the origin of the rudi- 
 mentary anlage which produces the parasite. In view of the facts concerning the 
 early stages of development the facts concerning maturation, fertilization and 
 segmentation of the ovum, and the formation of the germ layers there are two 
 possible and plausible modes of origin of the rudimentary anlage. (i) The 
 anlage of the parasite may be the result of the imperfect development of a 
 fertilized polar body. (2) The anlage of the parasite may be a special or an 
 isolated group of segmentation cells. 
 
 1. It is generally agreed that the polar bodies are abortive or rudimentary 
 ova extruded during the processes of maturation of the female sex cell; and that 
 these rudimentary ova probably contain the same morphological constituents 
 as the mature ovum itself. It is also known that in a few of the lower forms 
 the polar bodies arc capable of being fertilized and undergoing a considerable 
 degree of development, and that in some of the higher forms (rabbit, dog) the 
 spermatozoa may exist for some time inside the zona pellucida in the vicinity 
 of the polar bodies. In view of these facts it does not seem impossible that in 
 a few exceptional cases in Mammals the polar bodies may become fertilized 
 and produce rudimentary anlagen capable of giving rise to parasites. Such 
 an anlage would naturally lie in close proximity to the larger normal anlage 
 and might readily become attached to or finally enclosed within it. As a 
 more remote possibility, the polar body might become enclosed between the 
 blastomeres and thus finally produce the parasitic anlage within the meso- 
 dermal tissue where it might become an inclusion in some internal organ, 
 such as the genital gland. A polar body has been found between the blasto- 
 meres (rabbit). (Bischoff, Assheton, Bonnet.) 
 
 2. The view that the parasite may arise as the result of the development of a 
 special or an isolated group of segmentation cells has more advocates than the 
 view given in the preceding paragraph. One of the most interesting phases of 
 this theory is the view that tumors of the sexual glands, as well as those of other 
 regions, are the products of development of the germ cells as distinguished from 
 the somatic cells. In the skate it has been demonstrated that certain cells are 
 set apart at a very early period of development (during segmentation), which 
 are destined to give rise to the sex cells of the embryo, and which take no 
 part in its general development. Normally these special cells pursue a course 
 of development and differentiation which leads to the formation of the mature 
 sexual elements (ova or spermatozoa) of the individual, but do not participate 
 in its general development. From this one may conclude that the primitive 
 germ cell, the one set apart for the production of the mature sex cells, is, so 
 to speak, a sister to the embryo and is not a derivative of the embryo. It 
 seems not impossible that some aberrant members of this group of germ cells, 
 without undergoing the changes incident to maturation, might pursue a course 
 
604 TEXT-BOOK OF EMBRYOLOGY. 
 
 of development of their own accord and give rise to a rudimentary twin the 
 foetal inclusion or parasite. In this case one must regard the germ cells as pos- 
 sessing an inherent potentiality which may institute formative processes; but the 
 actual cause of the spontaneous development is unexplained. (Born, Wilson, 
 Morgan, Driesch, Schultze). 
 
 Another possible source of parasitic growths is suggested by experiments in 
 which some of the cells during segmentation have been separated from the 
 general mass. The artificially segregated cells may develop into perfect em- 
 bryos smaller than the normal, or into partial embryos. Further experiments 
 along the same line on the frog justify the assumption that the segregated cells 
 or masses may become enclosed within the developing larger embryo and there 
 undergo further growth and differentiation and give rise to inclusions or 
 parasites. (Roux.) 
 
 As a matter of fact there seems to be no good reason for considering any one 
 of the above views as expressing the only possibility as to the source of unequal 
 duplicities or parasitic growths. There is nothing to show that all three 
 methods may not contribute to the various kinds of duplicities including 
 certain teratomata of the sexual glands. 
 
 MALFORMATIONS INVOLVING ONE INDIVIDUAL. 
 
 Description, Origin. 
 
 While the more limited malformations and anomalies affecting individual 
 organs are discussed in the chapters dealing with those organs, it seems best 
 to consider here some of the gross malformations in a single individual, 
 especially those which affect the external form of the body. 
 
 DEFECTS IN THE REGION OF THE NEURAL TUBE. 
 
 The term cranioschisis has been given to a group of malformations, or 
 defects, in the roof of the skull and in the brain. Depending upon the degree 
 of defect, the group is divided into two classes acrania and hemicrania 
 which include conditions from a complete absence of the roof of the skull to 
 partial arrest of development. Associated with these conditions are varied 
 defects and malpositions of parts or of the whole of the brain. 
 
 In extensive acrania the entire roof of the skull is lacking, and the brain 
 and its membranes are reduced to small masses of tissue lying upon the floor 
 of the skull. The defect may also extend to the cervical vertebrae crania- 
 rachischisis. These vertebras remain open dorsally and are bent inward 
 (lordosis) . The ears are set upon the shoulders and the neck seems to be 
 lacking. 
 
TERATOGENESIS. 605 
 
 Sometimes the rudimentary brain shows traces of structures which the 
 normal brain possesses, and is raised above the level of the defective skull like 
 a turban acrania with exericephaly. With acrania are usually associated 
 facial clefts, defects in the eyes, etc. 
 
 The malformation known as hemicrania is limited to a part of the skull, 
 usually the posterior part. The brain mass often protrudes through an opening 
 in the cranial vault and forms a mass on the back of the head or hanging down 
 upon the neck hemicrania with exencephaly. 
 
 In the various forms of cephalocele or cerebral hernia the roof of the skull is 
 more nearly complete and the protrusion of the cranial contents is limited 
 to circumscribed areas. The protruding mass may consist of brain substance 
 only encephalocele, or of the membranes only mcningocele, or of both 
 meningoencephalocele. Sometimes the brain ventricles are distended by the 
 accumulation of fluid hydr encephalocele, or a sac formed by the membranes 
 may be distended by fluid hydromeningocele. 
 
 A condition known as hydrencephaly is sometimes met with. Fluid ac- 
 cumulates in the brain cavities after the skull is formed, causing a general 
 enlargement of both brain and skull, without hernia (congenital hydrocephaly) . 
 
 A combination of hydrencephaly and cephalocele may also occur. The 
 cervical vertebrae adjoining the skull are cleft dorsally and the protruding mass 
 lies in the cleft iniencephaly. 
 
 Hydromicrencephaly means an accumulation of fluid with a rudimentary 
 brain and a correspondingly small skull. 
 
 Porencephaly is a lower grade of hydromicrencephaly, in which fluid ac- 
 cumulates in the third and lateral ventricles and affects the adjacent frontal 
 and parietal lobes. If the individual lives with this malformation, the intellect 
 is impaired and the extremities contract and atrophy. 
 
 Microcephaly and micrencephaly go together as abnormal smallness of the 
 skull and brain. The brain, aside from the diminutive size, may not be de- 
 formed. These conditions, in which the body is of the usual size, should not 
 be confused with those found in dwarfs in whom the body also is small 
 (nanocephaly). 
 
 In the region of the spinal cord there is a group of malformations consisting 
 of varying degrees of clefts in the vertebral canal. The clefts may remain open 
 rachischisis or they may be covered by a sac-like prominence spina bifida 
 (spina bifida cystica, rachischisis cystica). Both forms of cleft may occur in 
 any region of the vertebral column and may be limited, or involve the entire 
 column. 
 
 The malformation known as rachischisis appears as a widely open groove 
 bounded laterally by rudimentary laminae of the vertebrae. The deformity may 
 include the entire vertebral column holorachischisis, or it may be confined to 
 
606 TEXT-BOOK OF EMBRYOLOGY. 
 
 a small part merorachischisis, and is usually accompanied by curvature of the 
 spine. Sometimes the deformity of the vertebral column is continuous with 
 cranioschisis craniorachischisis. The more or less rudimentary spinal cord 
 lies along the bottom of the cleft. When the rachischisis is total the spinal 
 cord is practically wanting amyelus. 
 
 Spina bifida is marked by the presence of a cyst which protrudes through a 
 cleft in the vertebral column; externally it presents the appearance of a sac- 
 like structure of variable size. Three different types of spina bifida may be 
 recognized, depending upon the structures involved. If the cord and its mem- 
 branes are included in the cyst it is known as myelomeningocele; if only 
 the membranes, as spinal meningocele; if the cord itself is dilated, as myelo- 
 cystocele. 
 
 Myelomeningocele is the most common form of spina bifida and usually 
 occurs in the lumbo-sacral region, rarely in the cervical or thoracic region. 
 Its appearance is that of a rounded tumor in the medial line, and, if the child 
 lives, the tumor increases in size and may become as large as a child's head. 
 The spinal cord is bent dorsally and attached to the sac. The pia mater and 
 arachnoid surround the cord, while the dura is incomplete. The spinous 
 processes and the adjacent parts of the arches of the vertebrae are absent. 
 From one to several vertebrae may be affected. 
 
 In spinal meningocele the spinal membranes bulge out to form a sac filled 
 with fluid. The vertebrae are not necessarily defective, for the sac may pro- 
 trude between the arches or through the intervertebral foramina; it more 
 often protrudes laterally than dorsally. The presence of meningocele is 
 not at all incompatible with life, but the sac usually enlarges to a good-sized 
 tumor. 
 
 In myelocystocele (syringomyelocele) the central canal of the spinal cord is 
 dilated locally, with the result that a portion of the cord with the pia and 
 arachnoid becomes a cystic tumor. It may occur in any region, and is fre- 
 quently associated with asymmetrical defects of the vertebral column. 
 
 Spina bifida occulta, a condition in which neither cleft nor tumor is visible 
 externally, is usually found in the lumbo-sacral region. The position of the 
 defect is indicated by a small depressed cicatrix or by a small tuft of hair. 
 The spinal cord is elongated and extends into the sacral canal. The spinal 
 canal is sometimes dilated and the cauda equina affected, in consequence of 
 which there are sensory and motor disturbances in the lower extremities. 
 Paralytic club-foot and derangement of the bladder functions may result 
 from such a deformity of the cord. 
 
 Diastematomyelia, or doubling of the spinal cord, sometimes accompanies 
 rachischisis. The cord in such cases is represented by two atrophic bands. 
 
TERATOGENESIS. 607 
 
 ORIGIN OF MALFORMATIONS IN THE REGION OF THE NEURAL TUBE. 
 
 Normally the neural tube is formed from a band of ectoderm extending 
 along the dorsum of the embryonic disk. The ectodermal band becomes 
 thickened, a groove appears along the middle line and the margins are raised 
 above the surface of the embryo, forming the neural groove. The margins of 
 the band continue to push upward and finally meet and fuse with each other 
 throughout their entire length in the middorsal line. The surface ectoderm 
 then breaks away from the line of fusion and forms a continuous layer upon the 
 dorsum of the embryo, thus leaving the neural groove, now the neural tube, 
 extending the entire length of the embryo immediately beneath the ectoderm. 
 
 The formation of the neural tube is a fundamental process, occurring 
 at an early period. It is obvious that any interference with its development 
 will be followed by serious defects in the nervous system and the structures 
 that immediately surround it. A most natural result of such interference would 
 be the failure of the two margins of the neural groove to unite, and it is not 
 improbable that the various forms of cranioschisis are the results of imperfect 
 or complete lack of closure of the cephalic end of the neural groove. Such 
 failure of the neural groove to close would leave the dorsum of the head region 
 open, so that not only the brain but also the cranial vault would be affected. 
 If the failure to close is complete, a high degree of acrania would result. In 
 case of partial closure some form of hemicrania might follow. 
 
 Rachischisis, with partial or total absence of the spinal cord, may also be 
 attributed to defective closure of the neural tube, total rachischisis being due to 
 complete lack of closure, partial rachischisis to partial lack of closure. 
 
 The origin of spina bifida has been a much discussed question. The earlier 
 view that the deformity was due to accumulation of fluid within the spinal canal 
 and rupture of the distended sac is now usually considered untenable. At the 
 present time it is generally agreed that spina bifida is closely related to defective 
 closure of the neural tube, although the exact nature of this relation is not 
 known. 
 
 According to one investigator the defective fusion of the margins of the 
 neural groove is due to deficient growth of the blastoderm (von Reckling- 
 hausen). Another view is that the separation between the neural tube and 
 the adjacent ectoderm is incomplete (Torneux). Still another investigator 
 considers the defective development due to some primary defect in the germ 
 (Ziegler). Experimental studies on the frog's egg suggest to another observer 
 that spina bifida is caused by defective closure of the blastopore (Hertwig). 
 Recently it has become possible to produce spina bifida at will in some of the 
 lower Vertebrates (frog, Axolotl) by treating the developing eggs with a solution 
 of sodium chlorid (Hertwig). At the same time other defects in the nervous 
 
608 TEXT-BOOK OF EMBRYOLOGY. 
 
 system (anencephaly) are produced. In these experiments the malformations 
 follow retarded closure or lack of closure of the neural tube. 
 
 DEFECTS IN THE REGION OF THE FACE AND NECK, AND THEIR ORIGIN. 
 
 Associated with malformations of the brain there is a group of defects which 
 involve the eyes and nose, and to which the term cydocephaly has been applied. 
 The cerebral hemispheres are derivatives of the fore-brain. Sometimes they 
 fail to develop properly and are represented by a single mass occupying a 
 considerable portion of the cranial cavity. The eyes primarily represent 
 lateral, symmetrical outgrowths from the fore-brain vesicle. If the cerebral 
 hemispheres fail to develop, the development of the eyes is profoundly influ- 
 enced. Instead of being widely separated there may be any degree of mal- 
 formation from a mere narrowing of the distance between them to a complete 
 fusion into a single organ within a single medial orbit synophthalmia or cyclo- 
 pia. Within this orbit the eye may possess double or partially blended cor- 
 neae, pupils, lenses, and optic nerves, or it may have single structures. 
 
 Since the fronto-nasal process, which plays an important part in the forma- 
 tion of the nose, depends for its normal shape upon the development of the fore- 
 brain region, various degrees of malformation of the nose almost invariably 
 accompany cyclopia. In a typical cyclops the nose is reduced to a fleshy mass 
 protruding from the frontal region. 
 
 It is not unusual to find clefts of the upper lip (hare lip) and of the palate 
 (cleft palate) associated with cyclopia; for the normal union of the fronto- 
 nasal and maxillary processes depends upon the development of the fore-brain 
 region. The branchial arches likewise may be affected with resulting mal- 
 formations of the mouth and external ear. The two ears may be united across 
 the ventro-medial line synotus or cydotus, and the mouth slit may be absent 
 cydostomus. 
 
 The eye may also be the seat of local defects. It may remain abnormally 
 small micr ophthalmia, or incompletely developed, or may be entirely lacking 
 anophthalmia. The eyelids may enclose an abnormally narrow fissure 
 ankyloblepharon, or the fissure may be wanting cryptophthalmia, or the lids 
 may be adherent to the eyeball symblepharon. Sometimes there is a cutaneous 
 fold which partly fills the inner canthus like the nictitating membrane in lower 
 forms epicanthus. 
 
 Malformations of the face are not uncommon, all such congenital defects 
 being due to incomplete fusion of the processes which form the jaws and 
 greater part of the face (see page 148). In extreme cases there is an early 
 and complete arrest of development of all the parts which normally form the 
 face aprosopus. Arrested development of the first pair of branchial arches 
 
TERATOGENESIS. 609 
 
 results in abnormally small lower jaws micrognaihy, or in almost complete 
 absence of the lower jaws agnathus; in the latter case the ears are brought 
 together in the ventro-medial line synotus. Rarely the mandible is partly 
 duplicated, due to the development of a secondary mandibular process 
 dignathus. 
 
 Clefts in the upper lip, maxilla and palate follow the lines of primary union 
 of the processes which form these structures (consult Figs. 136 and 137). The 
 cleft may affect the lip alone, may be single or double, but is always lateral 
 hare lip (cheiloschisis). It may affect the lip and maxilla (cheilognathoschisis) , 
 or the lip, maxilla and palate (hare lip and cleft palate, cheilognathouranos- 
 chisis). (For a further discussion of hare lip and cleft palate, see p. 212). 
 
 Occasionally there is an entire lack of union between the naso-frontal process 
 and the maxillary process. The result is an oblique cleft which extends up- 
 ward from the mouth oblique facial cleft (cheilognathoprosoposchisis) . The 
 processes which form the boundaries of the mouth slit (maxillary and mandib- 
 ular processes) sometimes fail to fuse to the normal extent, thus giving rise to 
 macrostomus; or the fusion may proceed beyond the normal limit, giving rise to 
 microstomus; rarely complete fusion of the processes on one side with each other 
 and with their fellows of the opposite side results in closure of the mouth slit 
 astomus or atresia oris. Clefts in the lower lip, due to imperfect union of the 
 two mandibular processes in the medial line, are rare. 
 
 The branchial arches (apart from the first which has already been con- 
 sidered) and the branchial grooves are also subject to defective developmental 
 processes. Malformations of the ear, with closure of the external auditory 
 meatus, due to abnormal development of the first groove and surrounding parts, 
 are sometimes met with either alone or in connection with other facial defects. 
 Cervical fistula are the results of imperfect closure of some of the grooves along 
 with rupture of the membranes that separate the bottoms of the external 
 grooves from the bottoms of the internal grooves or pharyngeal pouches. The 
 fistula may be complete, that is, there may be a communication between the 
 pharyngeal cavity and the exterior; or it may be incomplete, opening either 
 into the pharynx, or on the surface of the body. The internal opening of a 
 cervical fistula is usually in the lower part of the pharynx or in the posterior 
 palatine arch near the tonsil. The external opening varies in position. It is 
 usually situated near the sterno-clavicular articulation, or at the inner or 
 outer edge of the sterno-mastoid muscle. The majority of cervical fistulae are 
 probably derived from the second branchial groove. They all have the form of 
 narrow canals lined with mucous membrane. Medial cervical fistulae, the ex- 
 ternal openings of which are situated in the medial line, are rare. 
 
 It sometimes happens that during the closure of the branchial grooves por- 
 tions of the walls of the grooves becomes enclosed within the walls of the 
 
610 TEXT-BOOK OF EMBRYOLOGY. 
 
 pharynx, that is, within the sides of the neck. This abnormal process results in 
 various forms of cysts and tumors. The most common are simple retention 
 cysts, known as branchial or branchio genetic cysts, which vary from small 
 insignificant structures to large tumors. If derived from the external branchial 
 furrows, they are dermoid in character, lined with ectodermal derivatives, and 
 contain sebaceous material. If derived from the internal furrows, they con- 
 tain mucous fluid, the lining epithelium is likely to be columnar and is claimed 
 by some to be ciliated. 
 
 DEFECTS IN THE THORACIC AND ABDOMINAL REGIONS, AND THEIR ORIGIN. 
 
 As described elsewhere (see page 316), the digestive tube (primitive gut) and 
 ventral body wall are formed primarily by a bending ventrally and fusing of the 
 originally flat germ layers. The splanchnopleure on each side first bends 
 ventrally and fuses with its fellow of the opposite side in the medial line to form 
 the gut, and soon afterward the somatopleure likewise fuses in the ventro- 
 medial line to form the body wall. Naturally a defective fusion of the two 
 sides of the somatopleure would result in a more or less extensive medial cleft. 
 The cleft may be limited to a small portion of the abdomen or thorax, or may 
 extend from the neck to the pelvis. 
 
 When the cleft is very extensive and involves the thoracic and abdominal 
 walls, the condition is known as thoracogastroschisis. In this case most of the 
 viscera protrude through the cleft (ectopia viscerum) and are covered merely 
 by peritoneum. Spinal curvature of a low or high degree is usually associated 
 with the eventration. 
 
 The cleft may involve the entire abdominal wall gastroschisis completa 
 and the abdominal viscera may protrude through it. In a somewhat lesser 
 degree of fission, parts of the abdominal viscera, covered with peritoneum, 
 may protrude and form what is known as omphalocele. Not uncommonly 
 portions of the intestine and omentum protrude through an abnormally large 
 umbilical ring umbilical hernia. The region below the umbilicus is not in- 
 frequently the seat of fissures in the abdominal wall, through which the bladder 
 may protrude (ectopia vesicas) . Fissures in the thoracic wall vary in extent. 
 When the defect is extensive the heart and pericardium protrude through the 
 opening (ectopia cordis). 
 
 MALFORMATIONS OF THE EXTREMITIES. 
 
 Any degree of deficiency may exist, from total absence of extremities to 
 the lack of a single finger. The malformations, however, are not confined to 
 total or partial lack of members, for supernumerary fingers and toes are some- 
 times present. The following is the classification given by Piersol: 
 
TERATOGENESIS. 611 
 
 1. One or More Extremities Wanting. (a) Amelus. Both upper and lower 
 extremities are practically absent, (b) Abrachius, A pus. Either the upper or 
 lower extremities are wanting, the other pair often being well formed, (c) 
 Monobrachius, Monopus. One upper or one lower extremity is absent, the 
 others being fully developed. 
 
 2. One or More Extremities Defective. (a) Peromelus. All the extremities 
 are imperfect. A striking variety of this is the suppression of the proximal 
 segments of the extremities, the hands and feet being fairly well formed (phoco- 
 melus). (b) Perobrachius, Per opus. The former signifies defective develop- 
 ment of the upper, the latter of the lower extremities. 
 
 3. One or More Extremities Abnormally Small but well Formed. (a) Micro- 
 melus. All the extremities are diminutive, but without any other malformation, 
 (b) Microbrachius, Micropus. One or both upper extremities may be small, or 
 one or both lower. 
 
 4. Bones Defective or Absent. Such malformations are rare. 
 
 5. Loii'er Extremities Fused. (a) Sympus (symelus siren). The lower ex- 
 tremities are fused more or less completely, and the lower end of the trunk is 
 abnormal. The feet may be imperfect and double (sympus dipus) , or a single 
 foot may be present (sympus monopus), or the feet may be wanting (sympus 
 apus) . 
 
 6. Hands or Feet Defective. There is a great variety of malformations of the 
 hands and feet due to arrested development of some of the digits. The varia- 
 tions include all degrees of suppression from the shortening of a finger or toe to 
 almost total absence of digits. Fusions of two or more digits are not uncom- 
 mon. Occasionally a structure, suggesting the webs on the feet of some 
 aquatic animals, is present. 
 
 The condition known as polydactyly (an increase over the normal number 
 of digits) is occasionally met with. The increase may range from a partial 
 doubling of the distal segment of a finger or toe to a two-fold quota of digits. 
 Cases of ten digits are extremely rare, as are even cases of seven or eight. One 
 supernumerary finger or toe, rudimentary or complete, is not uncommon. The 
 extra digits may appear on a single hand or foot, or on both hands or feet, or on 
 all four extremities, not necessarily showing any symmetry. A statement of the 
 possible modes of origin of polydactyly will be found on page 213. 
 
 AMNIOTIC ADHESIONS. Many malformations affecting the embryo or foetus 
 have been included under this head. It has been generally thought that the 
 amnion might become attached to some part of the embryo in such a way as 
 to cause malformations by interfering with the normal processes of growth. 
 The amnion might become attached to the head and by interfering with 
 normal growth produce hare lip, facial clefts and generally serious disturb- 
 ances. Undue pressure on an extremity would cause it to be stunted, or 
 
612 TEXT-BOOK OF EMBRYOLOGY. 
 
 an encircling band of amniotic tissue might cause constriction or even ampu- 
 tation of some of the extremities, or of some of the digits. Under the same 
 head there might also be included certain disturbances possibly caused by the 
 umbilical cord. The cord by becoming wound around the neck or extremities 
 and interfering with development may even cause the death of the foetus. 
 
 Causes Underlying the Origin of Monsters. 
 
 Within the past century the old grotesque notions that monsters were the 
 results of supernatural influences or of sexual congress with lower animals have 
 been overthrown as teratology has been placed upon an embryological basis. 
 The very old belief that impressions on the maternal senses may influence the 
 development of the embryo is still held by those who possess little or no scien- 
 tific knowledge, and is not uncommon even among gynecologists and obstetri- 
 cians. While remarkable cases of coincidence have been recorded, there seems 
 to be no proof whatever that maternal impressions are reflected upon the child 
 in the uterus. On the other hand, there has gradually accumulated a large 
 amount of negative evidence obtained from experimental work. The results of 
 this work have been such as to indicate that external influences mechanical or 
 physico-chemical cause the production of monsters. 
 
 Opposed to the theory that monsters are due to external influences is the 
 view that their cause lies within the germ, that is, that some inherent defect in 
 the constitution of one or both of the parental germ cells is brought out in the 
 new organism that develops after their union. According to this theory, 
 therefore, heredity is the important factor in teratogensis. While the oc- 
 currence of defective conditions in the germ cells cannot be demonstrated, the 
 apparent influence of heredity in the production of malformations has long been 
 recognized. Certain malformations, even so great as to put the embryo or 
 foetus in the class of monsters, have been known to occur in families through 
 successive generations. Such cases may be mere coincidences, yet more prob- 
 ably they are indicative of hereditary influence. 
 
 All the theories, therefore, are concerned with the question "whether the 
 conditions that produce a monster are germinal and hereditary or are external influ- 
 ences acting upon a normal germ" (Mall). Some defend the germinal or 
 hereditary factor as the most potent cause in the production of malformations, 
 while others just as strongly advocate the view that normal or abnormal 
 development depends largely upon external factors. It does not seem possible 
 to deny the importance of heredity in the development of the normal organism; 
 nor, on the other hand, can the importance of external influence, of environ- 
 ment, upon normal development be denied. The same factors may be con- 
 sidered as active in abnormal development, and it does not seem that either 
 
TERATOGENESIS. 613 
 
 factor can reasonably be considered as the only cause in the production of 
 malformations. Granting, however, that both hereditary and external influ- 
 ences are at work in the production of monsters, it is still difficult to determine 
 the separate role of each factor; on the one hand, either influence may appear 
 capable of having produced some given anomaly; on the other, both of them 
 may have been responsible for its appearance. 
 
 The first phase of the theory of external influence was presented three- 
 quarters of a century ago when attempts were made to produce monsters. The 
 experiments led to the formulation of the mechanical theory, which, when applied 
 to human monsters, considers them as the results of mechanical influences upon 
 the embryo, such as the pressure caused by tight lacing or by contractions of the 
 uterus. This theory was gradually transformed into the view that amniotic 
 bands compress or constrict the embryo, thus bringing about malformations. 
 In its turn the latter supposition has recently been criticized and the view sub- 
 stituted that the amniotic adhesions are the results of malformations and not 
 the cause of them (Mall). 
 
 The theory of external influence seems recently to be losing ground in favor 
 of the physico-chemical theory. The latter has gradually been evolved during 
 the course of a great number of experiments on the production of malformations 
 and monsters among the lower forms of animals. It has gained ground because 
 certain definite malformations have been obtained by subjecting the living egg 
 or young embryo to unusual conditions. The experiments consist of interfering 
 in some way with the normal course of development. The interference may be 
 mechanical or chemical, or both, but is always of such a nature as to cause the 
 egg or embryo to develop under unnatural conditions either in an unnatural 
 environment or after having had some of its own substance wholly or partly 
 removed. The results obtained, the strange creatures which develop after 
 such interference, are not infrequently comparable with malformations and 
 monsters found among the higher animals, and they strongly suggest that mal- 
 formations among the higher forms of animal life are the results of similar in- 
 terference with the normal course of development of the egg. 
 
 THE PRODUCTION OF DUPLICATE (OR POLYSOMATOUS) MONSTERS. By 
 shaking sea-urchin ova when in the two-cell stage so that the blastomeres are 
 separated, each blastomere can be made to grow into a whole embryo. De- 
 pending upon the degree of separation, the two embryos will be separate or more 
 or less united forming a double monster. If sea-urchin ova are placed in a 
 mixture of equal parts sea-water and distilled water shortly after fertilization, 
 the cell membranes rupture and part of the protoplasm bulges out. When the 
 ova are replaced in normal sea-water cleavage begins and one of the two primary 
 nuclei wanders into the extruded protoplasm. Each nucleus with its proto- 
 plasm becomes an embryo, and the result is a double monster. If the outflow of 
 
614 TEXT-BOOK OF EMBRYOLOGY. 
 
 protoplasm originally occured in several places, each droplet produces an 
 embryo and the result is a triple or quadruple monster (Loeb). 
 
 Similar experiments have also been performed on Vertebrates. For example, 
 the two primary blastomeres of Amphioxus have been partly separated and 
 double monsters developed. The blastomeres in the four-cell stage have been 
 incompletely separated, resulting in double embryos of equal size, or triple 
 embryos, or quadruple monsters. Frog's eggs have been made to produce 
 double monsters by keeping them turned upside down after the morula stage; 
 the same result has also been produced by loosely tying a ligature in the furrow 
 between the two primary blastomeres. A most curious result has been obtained 
 by splitting the limb bud of a growing tadpole one or more times. Two or even 
 a cluster of limbs may develop where only one does normally (Tornier). 
 
 These few examples from the great number of experiments which have been 
 performed serve to show that great light can be thrown upon the problems of 
 teratogenesis by experimental embryology. While they do not prove that there 
 are no other possible modes of origin for malformations, they indicate the im- 
 portance of external influences upon development, and afford tangible evidence 
 in the study of monsters. 
 
 THE PRODUCTION OF MONSTERS IN SINGLE EMBRYOS. In single embryos 
 of the lower forms it is possible to produce by various means a great variety of 
 malformations, many of which are likewise comparable with malformations 
 found in human embryos. By placing recently fertilized eggs of Fundulus 
 in a 1.5 per cent, aqueous solution of potassium chlorid, embryos may be 
 produced in which the heart is developed but does not beat, and in which the 
 blood vessels appear in their normal positions but with irregular lumina (Loeb). 
 After extirpating the heart anlage from very young frog embryos, the latter grow 
 irregularly and become edematous; the larger vascular trunks are distended, 
 but the capillary system is imperfect or absent, and the development of many 
 other organs is inhibited (Knower.) Similar results may be obtained by 
 placing the young embryos in aceton-chloroform which inhibits the heart 
 action. 
 
 It is possible to produce typical spina bifida in frog embryos by putting 
 them, during the early stages of development, into a 0.6 per cent, solution of 
 sodium chlorid (Morgan and Tsuda). If the eggs of Axolotl are treated with 
 a 0.7 per cent, solution of sodium chlorid all the embryos have spina bifida 
 (Hertwig). If the eggs of Fundulus are placed in a solution of magnesium 
 chlorid, 50 per cent, of them produce embryos with cyclopia (Stockard). 
 
 Even these few examples from the enormous number of experiments that 
 have been tried in the study of single monsters again lead to the conclusion that 
 at least some malformations in single individuals are due to external influences 
 and not to germinal defects. 
 
TERATOGEXESIS. 615 
 
 THE SIGNIFICANCE OF THE FOREGOING IN EXPLAINING THE PRODUCTION 
 OF HUMAN MONSTERS. There is, of course, no way to obtain experimental 
 evidence for or against any theory so far as the human subject is concerned. 
 But it is possible to compare the results of experiments on the lower animals 
 with condions found in human embryos. So many malformed human embryos 
 resemble in a general way and often in detail the monsters in the lower forms 
 produced by experimental means that a probable similarity in the causation 
 of them at once suggests itself. The monsters in the lower forms are artifici- 
 ally produced by interfering with the normal course of development of the 
 egg, and by disturbing the normal conditions of nutrition and growth. The 
 disturbing factors are mechanical or chemical, or both. 
 
 According to the recent opinion of Mall, the primary disturbing factors in 
 man are not poisons in the maternal blood, corresponding with chemical agents 
 used in experiments, but the faulty implantation of the ovum in the uterine 
 mucosa. This means that, after the fertilized and segmenting ovum has 
 passed down the oviduct and entered the uterus, it fails to become properly 
 embedded in the mucous membrane. The immediate result is an imperfect 
 formation of the foetal coverings, especially of the chorion. 
 
 The reasons for the faulty implantation are not clear, but they are possibly, 
 even probably, to be found in the condition of the uterus. The most plausible 
 explanation is that some form of endometritis makes the uterine mucosa in- 
 capable of properly adapting itself for the reception of the ovum. 
 
 In the case of the human embryo, such an imperfection in the agency through 
 which it receives its nourishment might be considered in a sense analogous to 
 the external influences that produce monsters in the lower forms. 
 
 References for Further Study. 
 
 AHLFELD, F.: Die Missbildungen des Menschen. Leipzig, 1880-1882. 
 
 AHLFELD, F.: Lehrbuch der Geburtshilfe. Leipzig, 1903. 
 
 BALLAXTYXE, J. W.: Antenatal Pathology. 2 Vols. Edinburgh, 1904. 
 
 BARDEEX, C. R.: Abnormal Development of Toad Ova Fertilized by Spermatozoa 
 exposed to the Roentgen Rays. Jour, of Exp. ZooL, Vol. IV, 1907. 
 
 BEARD, J.: The Morphological Continuity of the Germ Cells in Raja batis. Anat. 
 Anz., Bd. XVIII, 1900. 
 
 COXKLIN, E. G.: The Cause of Inverse Symmetry. Anat. Anz., Bd. XXIII, 1903. 
 
 DARESTE, C.: Recherches sur la production des monstrosites. Paris, 1891. 
 
 DRIESCH, H.: Entwickelungsmechanische Studien. Zeitschr. /. wissensch. Zool., Bd. 
 LIII, Bd. LV. 
 
 FORSTER,: Die Missbildungen des Menschen. Jena, 1865. 
 
 HERTWIG, O.: Urmund und Spina bifida. Arch. /. mik. Anat., Bd. XXXIX, 1892. 
 
 HERTWIG, O.: Die Entwickelung des Froscheies unter dem Einfluss schwacherer und 
 starkerer Kochsalzlosungen. Arch. /. Mik. Anat., Bd. XLIV, 1895. 
 
616 TEXT-BOOK OF EMBRYOLOGY. 
 
 HERTWIG, O.: Missbildungen und Mehrfachbildungen. In Hertwigs Handbuch der 
 vergleich. u. experiment. Entwickelungslehre der Wirbeltiere, Bd. I, Teil I, 1903. 
 
 HIRST AND PIERSOL: Human Monsters. Philadelphia, 1891. 
 
 KNOWER, H. McE.: Effects of Early Removal of the Heart and Arrest of the Circulation 
 on the Development of Frog Embryos. Anat. Record Vol. VII, 1907. 
 
 LOEB, J.: Beitrage zur Entwickelungsmechanik der aus einem Ei entstehenden Doppel- 
 bildungen. Roux's Arch. /. Entwickelungsmechanik der Organismen, Bd. I, 1895. 
 
 LOEB, J.: Studies in General Physiology. Chicago, 1905. 
 
 MALL, F. P.: A Study of the Causes Underlying the Origin of Iiuman Monsters. Jour, 
 of Morphol, Vol. XIX, 1908. 
 
 MARCHAND, L.: Missbildungen. In Eulenburg's Real -Encyclopedic der gesammten 
 Heilkunde, Bd. XV, 1897. 
 
 MORGAN, T. H. : Half-embryos and whole Embryos from one of the first two Blastomeres 
 of the Frog's Egg. Anat. Anz., Bd. X, 1895. 
 
 MORGAN, T. H.: Ten Studies in Roux's Arch. j. Entwickelungsmechanik der Organ- 
 ismen, Bd. XV-XIX, 1902-1905. 
 
 PANUM: Entstehung der Missbildungen. Berlin, 1880. 
 
 PIERSOL, G. A. : Teratology. In Wood's Reference Handbook of the Medical Sciences, 
 Vol. VII, 1904. 
 
 SCHULTZE, O.: Die kiinstliche Erzeugung von Doppelbildungen bei Froschlarven mit 
 Hilfe abnormer Gravitationswirkung. Roux's Arch. /. Entwickelungsmechanik der 
 Organismen , Bd. I, 1895. 
 
 SCHWALBE, E.: Die Morphologic der Missbildungen des Menschen und der Thiere. 
 Jena, 1906-1907. 
 
 STOCKARD, C. R.: The Artificial Reproduction of a Single Median Cyclopean Eye in 
 the Fish Embryo by Means of Sea-water Solutions of Magnesium Chlorid. Roux's Arch, f 
 Entwickelungsmechanik der Organismen, Bd. XXIII, 1907. 
 
 TORNIER, G.: An Knoblauchskroten experimentell entstandene iiberzahlige Hintei 
 gliedmassen. Roux's Arch /. Entwickelungsmechanik der Organismen, Bd. XX, 1905. 
 
 WILDER, H. H.: Duplicate Twins and Double Monsters. American Jouc.of Ana". 
 Vol. Ill, 1904. 
 
 WILLIAMS, J. W.: Obstetrics. New York, 1903. 
 
 WILSON, E. B.: On Multiple and Partial Development in Amphioxus. Anat. Anz. 
 Bd. VII, 1893. 
 
INDEX 
 
 Abdominal cavity, 339, 377 
 
 regions, defects of, 610 
 Abducens, VI, nerve, 462, 464 
 Aberrant ductule, 417 
 Abnormal embryos, 154 
 Abrachius, 611 
 Acardia, 285, 595 
 Acardiaci, acephali, 596 
 
 acormi, 596 
 
 amorphi, 596 
 
 completi, 596 
 Acardiacus, 595 
 Accessory chromosomes, 28, 29 
 Achromatic spindle, 4 
 Acini, the, 443 
 Acoustic area (see also Auditory area), 558 
 
 ganglion, 588 
 
 VIII, nerve, 462, 465, 499, 500, 503, 
 518, 588 
 
 nerve, ganglion cells of, 589 
 
 radiation, 470, 471 
 Acrania, 604, 605, 607 
 
 with exencephaly, 605 
 Acrocephaly, 212 
 Acromion process, 199 
 Acrosome, 14 
 
 Acustico-facialis ganglion, 588 
 Acustico-lateral system, 
 
 influence on nervous system, 446, 459, 466 
 Adami, concerning hermaphroditism, 435 
 Adenoid tissue, 331 
 Adipose tissue, 167 
 Aditus laryngis, 360, 361 
 
 Afferent peripheral neurones, 447, 457, 489 to 
 502 
 
 peripheral nerve fibers, 451 
 
 root fibers, 451 
 After-birth, 133 
 
 After-brain (myelencephalon), 455 
 Agnathus, 356, 609 
 
 Ahlfeld's fission theory of symmetrical du- 
 plicity, 599 
 Air sacs, 365 
 Ala cinerea, 527 
 
 magna, 191 
 
 parva, 191 
 
 Alar plate, 477, 490, 512, 515, 519, 523, 527, 
 
 528 
 
 Albinism, 445 
 Albrecht, concerning formation of incisive 
 
 bone, 196 
 Alimentary tube, 316 
 
 intestinal region of, 317 
 
 cesophageal region of, 317 
 
 origin of, 316, 317 
 
 pharyngeal region of, 317 
 
 stomach region of, 317 
 
 yolk stalk of, 317 
 Alimentary tube and appended organs, 316 
 
 anomalies of, 354 
 
 histogenesis of gastrointestinal tract, 341 
 of liver, 349 
 of pancreas, 353 
 
 intestine, 337 
 
 liver, 345 
 
 mouth, 317 
 
 oesophagus, 335 
 
 pancreas, 350 
 
 pharynx, 329 
 
 salivary glands, 327 
 
 stomach, 335 
 
 teeth, 322 
 
 tongue, 320 
 Alisphenoid bone, 191 
 Allanto-chorion, 102 
 Allantoic blood-vessels, in Mammals, 104 
 
 duct, 114, 337 
 
 sac, 104 
 Allantois, the, 102 
 
 blood-vessels of, in chick, 103 
 in Mammals, 109 
 in man, 115 
 
 functions of, in chick, 102 
 in man, 114 
 
 in Mammals, 107 
 
 in man, 114 
 
 relation of, to chorion, 102 
 Allen, concerning sex cells, 404 
 Alopecia, 445 
 Alternation of vertebrae and myotomes, 180, 
 
 295 
 
 Amelus, 611 
 617 
 
618 
 
 INDEX 
 
 Amitosis, 3 
 
 diagram showing, 4 
 Amnion, false, 98 
 
 formation from amniotic fold, 97 
 
 in Birds, 95 
 
 in Mammals, 104, 106 
 
 in man, in 
 
 in Reptiles, 95 
 
 rhythmical contractions of, 98, 114 
 Amniotic adhesions, 611 
 
 cavity, 64, 97, in, 133 
 
 fluid, 112 
 
 folds, 96 
 
 in MammalyTnfy ~ 
 
 suture, 96 
 
 Amoeboid movement of nuclei, 2 
 Amphiaster, 4, 33 
 Amphibians, cleavage in, 42, 43 
 
 gastrulation in, 52 
 
 mesoderm formation in, 72 
 Amphicytes, 492 
 Amphimixis, 38 
 Amphioxus, cleavage in, 41 
 
 gastrulation in, 51 
 
 germ layers of, 71 
 
 mesoderm formation in, 68 
 Ampullae of semicircular canal, 583, 588 
 Amyelus, 606 
 Anal membrane, 341 
 
 opening, 341 
 
 pit, 34i 
 Anaphase, 6 
 Anencephaly, 313, 608 
 Angioblast, 269 
 Angiomata, 445 
 
 Angle of the mouth, 141, 148, 318 
 Angulus praethalamicus, 537, 540, 547 
 Ankyloblepharon, 608 
 Animal pole (micromere), 52 
 Animalculists, XIII 
 Annular placenta, 130 
 Anomalies, see also Terato genesis 
 
 of the alimentary tract, 354 
 
 of the diaphragm, 382 
 
 of the large vascular trunks, 287 
 
 of the heart, 285 
 
 of the integumentary system, 444 
 
 of the mesenteries, 382 
 
 of the muscular system, 313 
 
 of the nervous system, 560 
 
 of the omenta, 382 
 
 of the pericardium, 382 
 
 of the placenta, 130 
 
 Anomalies, of the respiratory system, 364 
 
 of the skeletal system, 209 
 
 of the umbilical cord, 131 
 
 of the urogenital system, 429 
 
 of the vascular system, 285 
 Anomalous position of the heart, 285 
 
 Anophthalmia, 608 , 
 
 Anterior colliculi, see Anterior corpora quad- 
 
 rigemina 
 Anterior (cerebral) commissure, 454 
 
 commissure of the cord, 503, 507 
 
 corpora quadrigemina, 467, 517, 530, 533, 
 576 
 
 horn (ventral gray column), 507 
 
 neuropore, 451 
 
 perforated space, 541 
 Anthelix, 591 
 Antitragus, 591 
 Aorta, dorsal, 218, 240 
 Aortae, primitive, 218 
 Aortic arches, 219, 241 
 Apathy, concerning peripheral nerves, 494 
 Apical body, 14 
 Apolar cells, 484 
 
 Appendage of the epididymis, 416 
 Appendicular skeleton, 198 
 
 anomalies of, 212 
 
 derivation of, 199 
 Appendix testis, 421 
 
 vermiform, 341 
 Aprosopus, 608 
 Apus, 6n 
 
 Aquaeductus Sylvii, 456 
 Arch of the aorta, 242 
 Archencephalon, 453 
 Archenteron, 51, 56 
 
 of Amphibians, 53 
 
 of Amphioxus, 5' 
 
 of Birds, 63 
 
 of Reptiles, 61 
 Archipallial commissure, see Fornix 
 
 commissure 
 Archipallium, 468, 505, 537, 541, 546 to 552 
 
 connections of, 505, 537, 558 
 Arcuate fibers (external), 515 
 
 (internal), 508, 515 
 Arcus aortae, 242 
 Area opaca, 61 
 
 pellucida, 61, 79 
 
 of supplemental cleavage. 60 
 
 vasculosa, 79, 101, 217 
 Areola, the, 443 
 Areolar tissue, 167 
 
INDEX 
 
 619 
 
 Arm, development of, 150 
 Arrectores pilorum, 438 
 Arteria centralis retinae, 569 
 Arteries, 240 
 
 allantoic, 222, 241 
 
 anomalies of, 287 
 
 basilar, 243 
 
 brachial, 248 
 
 carotid, 242 
 
 cerebral, 245 
 
 coeliac, 246 
 
 epigastric, 245 
 
 femoral, 249 
 
 gastric, 246 
 
 gluteal, 250 
 
 hepatic, 246 
 
 hyaloid, 569 
 
 hypogastric, 248 
 
 iliac, 247, 248 
 
 innominate, 243 
 
 intercostal, 245 
 
 internal spermatic, 247 
 
 lumbar, 245 
 
 mammary, 245 
 
 median, 248 
 
 mesenteric, 246 
 
 omphalomesenteric, 101, 103, 218, 246 
 
 ovarian, 247 
 
 peroneal, 250 
 
 popliteal, 249 
 
 pulmonary, 235, 243 
 
 radial. 249 
 
 renal, 247 
 
 saphenous, 249 
 
 sciatic, 249 
 
 splenic, 246 
 
 subclavian, 242, 244, 248 
 
 testicular, 247 
 
 tibial, 250 
 
 ulnar, 248 
 
 umbilical, 103, 222, 241 
 
 vertebral, 244 
 
 vesical, 248 
 
 vitelline, 101, 103, 218, 241 
 
 volar interosseous, 248 
 Articular cavity, 206 
 Aryepiglottic ridges, 361 
 Arytenoid ridge, 361 
 
 Ascaris megalocephala, for study of matu- 
 ration, 17 
 
 Assheton, concerning origin of parasitic duplic- 
 ity, 603 
 Aster, 2, 3, 7 
 
 Astomus, 609 
 Astragalus, the, 204 
 Asymmetrical duplicity, 610 
 
 origin of, 602 
 
 parasitic structures in the sexual glands, 
 
 601 
 
 Atlas, the, 184 
 Atresia of the anus, 357 
 
 oris, 609 
 Atria of heart, 231 
 
 of lungs, 365 
 Atrial septum, 233 
 Atrio-ventricular canal, 233 
 Atrium of inner ear, 583 
 Attraction cone, 36 
 
 sphere, 2, 3, 4 
 Auditory area of pallium, 470, 557, 558 
 
 meatus, external, origin of, 143, 147, 591 
 
 nerve, see Acoustic VIII 
 
 ossicles, derivation of, 197, 589 
 
 pit, 582 
 
 placode, 582 
 
 vesicle, 582 
 
 Auerbach, plexus of, 491 
 Aula, 542 
 Auricle, 590 
 
 Autonomic system (sympathetic), 458 
 Autosite, 600 
 Axial filament, 14, 20, 21 
 
 skeleton, 178 
 
 anomalies of, 209 
 head, 186 
 notochord, 178 
 primitive, 178 
 ribs, 184 
 sternum, 185 
 vertebrae, 179 
 
 thread, 14 
 
 Axis, (epistropheus), 184 
 Axone, the, 478, 485 
 
 Balfour, concerning peripheral nerves, 493 
 
 Bardeen, concerning peripheral nerves, 493 
 
 Bartholin's glands, 403 
 
 Basal plate, 125, 477, 502, 507, 512, 514, 524 
 
 Basilar artery, 243 
 
 Basioccipital bone, 190 
 
 Basisphenoid bone, 191 
 
 Basket cells, 529 
 
 Baskets, 529 
 
 Beard, concerning sex cells, 404 
 
 Bechterew, v., central tegmental tract of, 519 
 
 Belly stalk, 92, 114, 136 
 
620 
 
 INDEX 
 
 Bertini, columns of, 397 
 Bicornuate uterus, 433 
 Bielschowsky, method of staining, 563 
 Bilateral hermaphroditism, 434 
 Bile capillary, 349 
 Bipartite uterus, 433 
 Birds, cleavage in, 45 
 
 gastrulation in, 57 
 
 mesoderm formation in, 74 
 Bischoff, concerning origin of parasitic duplic- 
 ity, 603 
 Bladder (see also Urinary Bladder), 400 
 
 anomalies of, 431 
 Blastema, metanephric, 392 
 Blastemal stage, 180 
 Blastocyst, 49 
 Blastoderm, 57, 59, 133 
 Blastodermic vesicle, 134 
 Blastomeres, 40 
 Blastopore, 51 
 
 (crescentic groove), 59 
 Blastula, 47, 133 
 Blood, cells of, 267 
 
 relation of maternal and foetal blood in 
 
 Mammals, 109 
 in man, 115, 127 
 Blood cells, development of, 267 
 
 erythroblasts, 270 
 
 erythrocytes, 270 
 
 haemoblasts, 268 
 
 histogenesis of, 267 
 
 leucocytes, 270 
 
 lymphoblasts, 268 
 
 lymphocytes, 270 
 
 megaloblasts, 270 
 
 mesamceboid, 269 
 
 mononuclear leucocytes, 270 
 
 normoblasts, 270 
 
 primitive, 217, 268 
 lymphocytes, 268, 269 
 
 table showing development of, 273 
 Blood islands, 217, 268 
 Blood plates, 273 
 Blood vascular system, 216 
 Blood vessels, allantoic, function of, 104 
 
 arteries, 240 
 
 factors in development of, 226 
 
 heart, 227 
 
 origin of, 224 
 
 placental, 127 
 
 sinusoids, 260 
 
 veins, 250 
 Blue babies, 287 
 
 Body cavity, see Ccelom 
 Bone, compact, 172 
 
 diaphysis of, 176 
 
 epiphysis, 176 
 
 growth of, 176 
 
 intracartilaginous, 172 
 
 shaft of, 176 
 
 spongy, 171 
 
 subperiosteal, 172 
 Bone cells, 171 
 
 destroyers, 171 
 
 formers, 171 
 
 marrow, 177 
 Bones, defective or absent, 6n 
 
 derived from the branchial arches, 194 
 
 membrane, of the skull, 192 
 Bonnet, concerning derivation of pigmented 
 layer of retina, 577 
 
 concerning double origin of vitreous, 575 
 
 concerning the Erganzungshohle, 55, 56 
 
 concerning the Erganzungsplatte, 56 
 
 concerning gastrulation, 51 
 
 concerning origin of parasitic duplicity, 603 
 
 concerning the primitive intestinal cord, 62 
 
 concerning the primitive streak, 61 
 Born, concerning potentiality of germ cells, 604 
 Boveri, concerning the "dynamic center" of 
 
 the cell, 8 
 
 Bowman, membrane of, 578 
 Bowman's capsule, 387, 395 
 Brachia, anterior, 530, 533 
 Brain, the, 453, 473 
 
 after-brain (myelencephalon), 455 
 
 aquaeductus Sylvii, 456 
 
 archencephalon, 453 
 
 cephalic flexure of, 454 
 
 cerebellum, 455, 477, 512, 525 
 
 corpora striata, 455, 467, 474, 478, 539, 54* 
 
 defects in, 604, 605 
 
 deuterencephalon, 453 
 
 diencephalon, 455, 467, 474, 478, 531 
 
 distinguishing features of human and 
 their biological significance, 468, 470 
 
 end-brain (telencephalon), 455 
 
 epichordal part of, 453, 457 
 segment al, 512 
 
 fore-brain (.prosencephalon), 454 
 
 hind-brain (metencephalon), 455 
 
 inter-brain (diencephalon), 455 
 
 isthmus, 455, 513 
 
 medulla oblongata, 477, 512 
 
 mid-brain (mesencephalon), 454 
 
 plica encephali ventralis, 453 
 
INDEX 
 
 621 
 
 Brain, plicarhombo-mesencephalica, 475 
 prechordal part, 453, 457 
 rhinencephalon, 455, 467, 505, -537, 54 
 
 to 541 
 
 rhombic (rhombencephalon), 454 
 rhombo-mesencephalic fold of, 454 
 segmental, 457 
 
 character of, 456, 457 
 telencephalon, 455, 467, 538, to 561 
 ventral cephalic fold, 453 
 ventricles of, 456, 478, 542 
 Branchial arches, malformations of, 608 
 arches, origin of, 140, 146 
 cysts, 6io 
 
 epithelial bodies, 331 
 glomus caroticum, 335 
 parathyreoids, 332 
 thymus, 333 
 thyreoid gland, 331 
 grooves, origin of, 140, 146 
 Branchiogenetic cysts, 610 
 Branchiomeric muscles, 302 
 segmentation, 460, 489 
 Brachium, conjunctivum, see Superior cere- 
 
 bellar peduncle 
 
 pontis, see Middle cerebellar peduncle 
 quadrigeminum inferius, 471 
 Brandt, concerning anomalies of hair, 445 
 Bremer, concerning spinal accessory nerve, 496 
 Brodmann, concerning cortical layers, 556 
 Bronchial rami, 364 
 Brunner, glands of, 343 
 
 Bryce-Teacher's ovum, 86, 90, 92, in, 117 
 Bucco-nasal membrane, 580 
 Burdach, columns of, 459, 471, 518 
 
 nuclei of the columns of, 459, 466, 467, 
 
 520 
 Bursa pharyngea, 331 
 
 Caecum, the, 337, 340 
 
 Cajal, concerning development of cerebellar 
 cells, 548 
 
 concerning neurofibrils and early develop- 
 ment of nerve cells, 484, 485 
 
 concerning optic nerve, 576 
 
 concerning peripheral nerves, 494 
 Calcaneus (os calcis), 204 
 Calcar avis, 553 
 Calcarine area, 470 
 Calcification centers, 169, 173 
 
 zone, 172, 174 
 Calyces, 393 
 Campbell, concerning cortical areas, 559 
 
 Canal of Cloquet, 576 
 
 of Petit, 578 
 Canalized fibrin, 122 
 Canals of Gartner, 416 
 Capillaries, villous, 127 
 Capitulum of rib, 185 
 Capsule of Glisson, 346, 374 
 Carotid arteries, 242 
 
 gland, 429 
 
 skein, 429 
 Carpal bones, 200 
 
 Carpenter, concerning ciliary ganglia, 501 
 Cartilage, 168 
 
 cuboid, 204 
 
 cuneiform, 204 
 
 episternal, 185 
 
 ethmoidal, 192 
 
 laryngeal, 362 
 
 MeckePs, 189, 194 
 
 of hip bone, 203 
 
 thyreoid, 362 
 
 triticeous, 362 
 
 Wrisberg's, 363 
 Cartilaginous primordial cranium, 188 
 
 stage, 1 80 
 Cauda equina, 512 
 Caudal gut, 342 
 
 lymph sac, 275, 279 
 "Caul," 113 
 Cavity, abdominal, 377 
 
 amniotic, 64 
 
 body, 370 
 
 completion, 55, 56, 59 
 
 extraembryonic body, 92, 370 
 
 invagination, 59 
 
 parietal, 227, 372 
 
 pericardial, 370, 371 
 
 peritoneal, 370, 373 
 
 pleural, 370, 373 
 
 primitive pericardial, 84, 227, 230, 371 
 
 segmentation, 47, 54, 59 
 Cell, the typical animal, i 
 
 centrosome of, i, 3 
 
 diagram of, 2 
 
 functions of, 3 
 
 nucleus of, i 
 
 structure of, i 
 Cell division, 3 
 
 direct or amitosis, 3 
 
 indirect, or mitosis, 4 
 
 references for further study of, 9 
 Cell migration, of nervous system, 478, 
 479, 484, 485, 486, 519, 527 
 
622 
 
 INDEX 
 
 Cell-plate, 8 
 
 Cell proliferation, 479, 514, 519, 527 
 
 in neural tube, 479 
 Cells, air, 365 
 
 apolar of neural tube, 484 
 
 association, 457, 468, 528, 558, 530, 558 
 
 basket, 529 
 
 bipolar of neural tube, 484 
 of retina, 573 
 
 blood, 267 
 
 bone, 171, 174 
 
 chromaffin, 426 
 
 cochlear ganglion, 589 
 
 cone, 501, 505, 572, 573 
 
 daughter, 3 
 
 decidual, 123 
 
 dermal, 442 
 
 ependyma, 481, 483 
 
 epithelial, 479 
 
 fat, 1 68 
 
 female germ, 21 
 
 follicular, 408 
 
 germ, 10 
 
 germinal of neural tube, 479, 483 
 
 giant, 177 
 
 granule, 548 
 
 hair, 586, 588, 589 
 
 heart-muscle, 293, 312 
 
 Hensen's, 588 
 
 indifferent, 404 
 
 of neutral tube, 484 
 
 interstitial, 412 
 
 liver, 349 
 
 lutein, 31, 
 
 lymphoid, 335 
 
 male germ, 21, 25 
 
 mastoid, 590 
 
 mesodermal, 370, 438 
 
 mitral, 505 
 
 monopolar, 485 
 
 Miiller's, 572 
 
 myelocytes, 178, 272 
 
 myoblasts, 307 
 
 neuroglia, 481, 483 
 
 odontoblasts, 325 
 
 of Sertoli, 17, 21 
 
 osteoblasts, 171 
 
 osteoclasts, 171 
 
 phaeochrome, 426 
 
 pillar, 588 
 
 polymorphous, 557 
 
 Purkinje, 527 
 
 pyramid, 555, 556, 558 
 
 Cells, rod, 501, 505, 572, 573 
 
 sex, 404 
 
 solitary, of Meynert, 558 
 
 somatic, 101 
 
 spermatids, 17, 19, 28 
 
 spermatocytes, 17 
 
 spermatogenic, 17 
 
 spermatogonia, 17, 24 
 
 supporting, 17, 21 
 
 sustentacular, 572 
 
 vestibular ganglion, 589 
 
 wandering, 354 
 
 yolk, 53 
 
 (or merocytes), 59 
 Cement substance, origin of, 165 
 Central canal, 509 
 
 spindle, 4 
 
 fibei s of, 6 
 Centralis, 526 
 
 Centriole, the, 2, 3, 4, 5, 6, 7, 8 
 Centrolecithal ova, 44 
 Centrosome, the, 3, 8, 19 
 
 in fertilization, 34 
 Centrosphere, 3, 4 
 Cephalic flexure, 139, 454, 473 
 Cephalization, 450 
 Cephalocele, 605 
 Cephalopagus, 598 
 Cephalothoracopagus diprosopus, 597 
 
 janiceps, 598 
 
 Cerebellar hemispheres, 472, 526 
 Cerebellum, 455, 457, 466, 512, 525 
 
 afferent connections of, 466 
 
 basket cells of, 529 
 
 cells of Purkinje, 527, 529 
 
 centripetal fibers of, 529 
 
 climbing fibers of, 530 
 
 cortex of, 527 
 
 efferent connections of, 466 
 
 flocculi, 526 
 
 granular layer of, 527 
 
 granule cells of, 528 
 
 hemispheres of, 472, 526 
 
 lobes of, 526 
 
 middle peduncle of, 466, 472 
 
 molecular (plexiform) layer, 527 
 
 mossy fibers, 530 
 
 nodule, 526 
 
 parallel fibers of, 528 
 
 peduncles of, 466, 471, 473, 523, 530 
 
 postnatal development, 528, 529 
 
 superior peduncle of, 466 
 
 taenia of, 513 
 
INDEX 
 
 623 
 
 Cerebellum, velum of, 513 
 
 vermis of, 526 
 
 Cerebral hemispheres (see also Pallium), 457, 
 470, 474, 538, 541 to 560 
 
 hernia, 605 
 
 Cerebrospinal ganglia, 451 
 Cervical depression, 142 
 
 enlargement, 459 
 
 fistulae, complete, 609 
 incomplete, 609 
 
 flexure, 140, 478 
 Cervix, the, 415 
 
 plicae palmatae of, 415 
 Chalaza, 13 
 
 Cheilognathoprosoposchisis, 609 
 Cheilognathoschisis, 609 
 Cheilognathouranoschisis, 609 
 Cheiloschisis, 609 
 
 Chiari, concerning sebaceous cysts, 445 
 Chiasma eminence, 454 
 Chin, origin of, 144 
 Choanen, primitive, 580 
 
 Chondrification first occurrence in head skele- 
 ton, 1 88 
 Chondrocranium, 189 
 
 ossification of, 190 
 Chorda (see also Notochord), 68 
 
 anlage, 87 
 
 dorsalis, 178 
 
 tympani, 462, 498 
 Chordae tendinae, 237 
 Chordal plate, 68 
 
 sheath, 178 
 
 Chorio epitheliomata, 432 
 Chorioid, defective pigmentation of, 445 
 
 fissure, of pallium, 547 
 
 fold, 547 
 
 of rhombencephalon, 543 
 
 of eye, 575 
 
 plexus of fourth ventricle, 453, 513, 525 
 of lateral ventricle, 453, 533, 543, 547 
 of third ventricle, 453, 533 
 Chorioidal fissure of eye, 567, 575 
 Chorion, in chick, 103 
 
 in Mammals, 104, 106 
 
 in man, 115, 135 
 
 primitive, 98 
 function of, 103 
 
 relation of, to allantois, 115 
 Chorion frondosum, 118, 120 
 
 laeve, 118, 120 
 Chorionic villi, no, 118 
 
 in von Spec's embryo, 88 
 
 Chromaffin cells, 426 
 
 granules, 426 
 Chromatin, i 
 
 Chromophilic bodies, 478, 489 
 Chromosomes, 5, 6, 7 
 
 accessory, 28, 29 
 
 diploid number of, 17, 22, 24 
 
 haploid number of, 18, 22 
 
 identity of, 7, 26 
 
 qualitative differences in, 26 
 
 synapsis of, 18, 22, 26 
 
 U or V shaped, 5, 6 
 Chryptorchism, 432 
 Cilia, of the cells of gastrula, 51 
 Ciliary body of eye, 577 
 
 ganglion, 501 
 Circulation, changes in, at birth, 265 
 
 allantoic, 223, 240 
 
 foetal, course of, 265 
 
 reversal of, 595 
 
 vitelline, 220 
 Circulus arteriosus, 243 
 Cisterna chyli, 275 
 Clark, W. C., concerning the joint capsule 
 
 and cavity, 209 
 Clarke's columns, 466, 511 
 Clava, 524 
 Clavicle, 200 
 Cleavage (segmentation), 40 
 
 discoidal, 40, 45, 47 
 
 equal, 40, 41 
 
 forms of, 40 
 
 holoblastic, 40, 41, 46 
 
 meroblastic, 40, 44 
 
 in Amphioxus, 41 
 
 in Birds, 45 
 
 in the frog, 42, 43 
 
 in Mammals, 48 
 
 in man, 85 
 
 in Synapta, 41 
 
 of ova of opossum, 49 
 of rat, 50 
 
 references for further study of, 50 
 
 superficial, 40, 44 
 
 unequal, 40, 42 
 Cleft palate, 212, 608, 609 
 Climbing fibers, 530 
 Clitoris, the, 424 
 Cloaca, the, 341, 400 
 
 persistence of, 357 
 Cloacal membrane, 400 
 Closed skein, 5 
 Closing plate, 125 
 
624 
 
 INDEX 
 
 Coccygeal gland, 285 
 Cochlea, 460, 467 
 Cochlear ganglion cells, 589 
 of VIII nerve, 499 
 
 part of acoustic (auditory) nerve, 462 
 pouch, 583 
 terminal nuclei, 466 
 Coelenteron (see also Archenterori) , 51 
 Coelom (myocoel), 70, 370 
 
 embryonic, 370 
 Collaterals, 504, 529, 556 
 Colloid secretion of thyreoid gland, 331 
 Colon, the, 338 
 ascending, 34<y 
 descending, 340 
 sigmoid, 340 
 transverse, 340 
 Colostrum corpuscles, 444 
 Column cells, 503 
 heteromeric, 503 
 tautomeric, 503 
 Columns, anterior white, 507 
 
 dorsal gray (posterior horn) 458, 507 
 posterior white, 490, 503, 507 
 Columns of Bertini, 397 
 
 of Burdach, 459, 471, 418 
 
 nuclei of, 459, 471, 520 
 
 of Goll, 459, 471, 510, 518 
 
 nuclei of, 459, 471, 520 
 
 Commissura habenularis, 455, 538 
 
 mollis (see Massa intermedia'), 535 
 Commissural column cells, 503 
 Commissure, anterior, (cerebral), 454 
 neopallial, 468 
 posterior, 454, 533, 538 
 Completion cavity (see also Erganzungshohle), 
 
 55, 56 
 plate (see also Erganzungsplatte), 56, 59, 
 
 68 
 
 Concha, 144, 147 
 Conchae, inferior, 192 
 middle, 192 
 superior, 192 
 Cones, 501, 505, 572, 573 
 Confluens sinuum, 252 
 Conjugation, 38 
 Connective tissue follicle, 440 
 tissues, the 161 
 adipose, 167 
 areolar, 167 
 cartilage, 168 
 development of the, 161 
 embryonic, 167 
 
 Connective tissues, fibers of, 166 
 fibrillar forms, 166 
 ground substance of, 166 
 histogenesis of, 163 
 intermuscular, 310 
 osseous, 169 
 osteogenetic, 171 
 periosteum, 171 
 Contractile fibrils, 294 
 Contractions, rhythmical, of the amnion, in 
 
 man, 112 
 
 Convolutions of cerebral hemispheres, 542 
 Coordinating centers, higher, see Supraseg- 
 
 mental structures 
 Coordination, 447 
 Coracoid process, 199 
 Cords, medullary, 406 
 Pfliiger's egg, 408 
 rete, 404 
 sex, 405, 406 
 Cornea, 578 
 
 elastic membranes of, 578 
 endothelium of Descemet, 578 
 membrane of Bowman, 578 
 substantia propria corner, 578 
 Cornu ammonis, 548, 552 
 Corona radiata, n 
 
 of cerebral hemispheres, 537 
 Coronoid process, 196 
 Corpora quadrigemina, 467, 517, 530 
 anteria brachia of, 530 
 layers of, 530 
 Corpus albicans, 31 
 
 callosum, 468, 543, 550, 558 
 genu of, 551 
 splenium of, 551 
 haemorrhagicum, 30 
 luteum, 31 
 changes in, 32 
 false, 32 
 
 of pregnancy, 32 
 true, 32 
 
 Luysii, 537, 538 
 sterni, 186 
 
 striatum, 455, 467, 477, 478, 539, 541 
 crura of, 539, 541, 543 
 tail (cauda), 543 
 
 Correns, concerning determination of sex, 435 
 Cortex, cerebral, 554 
 Cortical layer of telencephalon, 542 
 Cortico-pontile fibers (of the pes), 466, 471, 
 
 472, 524, 558 
 Cord's organ, 460, 467, 558, 587 
 
INDEX 
 
 625 
 
 Costal process, 180 
 
 Cotyledon (lobe), 127 
 
 Cotyledons, 123 
 
 Covering layer of blastula (trophoderm) (see 
 
 also Enveloping layer), 48 
 Cowper's glands, 403 
 Cranial cavity, development of, 171 
 Craniopagus, 598 
 
 parasiticus, 598 
 Craniorachischisis, 606 
 Cranior-rachischisis, 604 
 Cranioschisis, 604, 607 
 Crescentic form of embryo, 140, 143 
 
 groove, of Reptiles, 59 
 Crescents of Gianuzzi, 329 
 Cribriform plate, 192 
 Cricroid cartilage, 197 
 Crista ampullaris, 586, 589 
 
 galli, 192 
 
 Crown-rump length, 153 
 Crusta, see Pes pedunculi 
 Cryptophthalmia, 608 
 Cuboid cartilage, 204 
 Culmen, 526 
 Cumulus ovigerus, 410 
 Cuneiform cartilages, 204 
 
 ridge, 361 
 Cuneus of cerebral hemispheres, 554 
 
 of medulla, 524 
 Cutis plate, 71, 163, 164, 293 
 Cuvier, ducts of, 222, 251, 253 
 Cyclocephaly, 608 
 Cyclopia, 560, 589, 598, 608 
 Cyclostomus, 608 
 Cyclotus, 608 
 
 Cylinder furrow of His, 509 
 Cylindrical form of body, 137 
 Cystadenomata, 433 
 Cystic tumors, 60 1 
 Cysts, 432, 
 
 dermoid, 445 
 
 sebaceous, 445 
 Cytoplasmic plate, 8 
 Cyto-trophoderm, 117, 121, 122 
 
 Darkschewitsch, nucleus of, 517 
 Daughter cells, 3 
 
 nuclei, 4, 6 
 Decidua, 116 
 
 basalis, 120 
 
 capsularis, 119 
 
 parietalis, 119 
 Decidual cells, 123 
 
 Decussation of Forel, 517 
 
 of Meynert, 530 
 DeFormatione Foetus, XIII 
 De Formato Fcetu, XIII 
 de Graaf, Regnier, XIII 
 de Graaf, Regnier, concerning the Graafian 
 
 follicle, XIII 
 
 Deiter's nucleus, tracts from 466, 511, 517 
 Dendrites, 485 
 
 apical, 555 
 
 of pyramidal cells, 556 
 Dens, the (odontoid process), 184 
 Dental groove, 323 
 
 papilla, 323 
 
 sac, 326 
 
 shelf, 323 
 Dentinal canals, 326 
 
 fibers, 326 
 
 pulp, 323, 325 
 Dentine, 32.3, 325 
 
 formation, 326 
 Dermal navel, 101, 112 
 
 umbilicus, 101 
 Dennis, the, 438 
 
 arrectores pilorum, 438 
 
 pigment of, 438 
 
 tactile corpuscles of Meissner of, 438 
 
 tunica dartos, 438 
 Dermoid cysts, 445, 601 
 Descemet, membrane of, 578 
 Descent of ovary, 422, 437 
 
 of testicle, 419, 437 
 Determination of sex, 27 
 Deuterencephalon, 453 
 Deutoplasm, i, 12, 13 
 Dextrocardia, 286, 355 
 Diaphragm, the, 370, 375 
 
 anomalies of, 382 
 
 caudal migration of, 376 
 
 changes in position of, 376 
 
 ligaments of, 376 
 
 muscular elements of, 300 
 
 primary, 374 
 
 Diaphragmatic hernia, 382 
 Diaphysis, 176 
 Diaplexus, 533 
 Diarthrosis, 207 
 Diastematomyelia, 606 
 Diaster, 6 
 Diatela, 533 
 Dibrachius, 597 
 Dicephalus, 598 
 Didelphys, uterus, 433 
 
626 
 
 INDEX 
 
 Diencephalon (inter-brain), 84, 455, 467, 474, 
 478, 531 to 538 
 
 epithalamus, 467, 468, 505, 536 
 
 hypophysis, 467, 533 
 
 hypothalamus, 467, 468, 478, 531, 533 
 
 nuclei of, 467 
 
 Rathke's pouch, 531 
 
 sulcus hypothalamicus, 531 
 Monroi, 531 
 
 thalamus, 467, 478, 505, 536 
 Diffuse nucleus, 2 
 Digits, beginnings of, 143 
 
 defects or absence of, 611 
 Diploid number of chromosomes, 17, 22, 24 
 Diprosopus, 598 
 
 diophthalmus, 598 
 
 monostomus, 598 
 
 tetrophthalmus, 598 
 
 triophthalmus, 598 
 Dipygus parasiticus, 597 
 Discoidal placenta, no 
 Disse, concerning olfactory nerve, 581 
 Diverticulum of Nuck, 422 
 Dollinger, XIII 
 Dorsal flexure, 139 
 
 mesogastrium, 378 
 
 septum of spinal cord, 510 
 Dorso-, lateral plate, see Alar plate 
 Double heart, 286 
 Driesch, concerning potentiality of germ cells 
 
 604 
 
 "Dry" labor, 113 
 Ducts, allantoic, 114, 337 
 
 alveolar, 365 
 
 cochlear, 586 
 
 Cuvier's, 222, 251, 253, 373 
 
 cystic, 346 
 
 deferent, 416 
 
 ejaculatory, 416 
 
 endolymphatic, 583 
 
 hepatic, 346 
 
 lacrymal, 579 
 
 mesonephric, 386, 400 
 
 Miillerian, 399, 413, 417 
 
 of the epididymis, 416 
 
 oviduct, 414 
 
 pronephric, 384, 385 
 
 reuniens, 586 
 
 Santorini's, 3*51 
 
 seminiferous, 402 
 
 Steno's, 327 
 
 thoracic, 275, 279 
 
 thyreoglossal, 331 
 
 Ducts, utriculosaccular, 586 
 
 Wharton's, 328 
 
 Wirsung's 351 
 
 Wolffian, 386 
 Ductule, aberrant, 417 
 
 efferent, 417 
 Ductus arteriosus, 238, 243, 267 
 
 choledochus, 346 
 
 pleuro-pericardiacus, 372 
 
 venosus, 256, 260 
 Duodenum, the, 337, 338 
 
 change of position of, 380 
 Duplicate monsters, 593 
 
 asymmetrical duplicity, 600 
 
 Marchand's scheme of, 593 
 
 symmetrical duplicity, 594 
 
 teratoid tumors, 594 
 
 true parasitic duplicity, 600 
 Duplicity incomplete, 598 
 Duval, concerning formation of primitive 
 
 streak, 61 
 Dyads, 18, 22 
 Dynamic center, 8 
 
 Ear, 450, 457, 462, 467, 506, 582 
 anomalies of, 591, 609 
 cochlea, 460 
 
 Corti's organ, 460, 467, 558, 587 
 external, 582, 590 
 internal, 582 
 labyrinth, 460 
 middle, 582, 589 
 Ear, inner, 
 
 acoustic nerve, 588 
 atrium, 583 
 auditory pit, 582 
 
 placode, 582 
 
 vesicle (otocyst), 582, 583 
 cells of, 588 
 cochlear pouch, 583 
 ducts of, 586 
 
 endolymphatic appendage of, 583 
 fenestra cochleae (rotunda), 587 
 
 vestibuli (ovalis), 587 
 membrana tectoria, 588 
 organ of Corti, 587 
 perilymph, 586 
 perilymphatic space, 586 
 saccule, 586 
 scala media, 586, 587 
 
 tympani, 586, 587 
 
 vestibuli, 586, 587 
 semicircular canals of, 583 
 
INDEX 
 
 627 
 
 Ear, inner, spiral lamina, 587 
 
 utricle, 586 
 
 vestibular membrane (of Reissner), 587 
 
 pouch, 583 
 Ear, middle, 589 
 
 Eustachian tube, 590 
 
 incus, 589 
 
 malleus, 589 
 
 mastoid cells, 590 
 
 stapes, 589 
 Ear, outer, 590 
 
 anthelix, 591 
 
 antitragus, 591 
 
 auricle, 591 
 
 external auditory meatus, 590 
 
 helix, 591 
 
 lobule, 591 
 
 tragus, 591 
 
 tubercles of, 591 
 
 tympanum, 591 
 Ectoderm (epiblast), 51, 133 
 
 formation of, 51 
 
 in Amphibians, 54 
 
 in Amphioxus, 51, 52 
 
 in Birds, 60, 62 
 
 in frog, 56 
 
 in Mammals, 64 
 
 in Triton, 53, 54 
 
 in Reptiles, 58 
 Ectopia cordis, 211, 286, 382, 610 
 
 vesicae, 610 
 
 viscerum, 610 
 
 of the kidneys, 429 
 Ectopic gestation, 30 
 Ectoplasm, 170 
 
 Edinger, concerning the oral sense, 468 
 Effectors, 448, 451, 457 
 Efferent ductules, 416 
 
 peripheral nerve fibers, 452 
 
 peripheral neurones, 447, 457, 486 to 489 
 
 root fibers, 486 
 Egg (see also ovum), 10 
 
 cleavage in hen's, 45 
 
 diagram of hen's, 13 
 
 nests, 408 
 
 cords, Pfiuger's, 408 
 protoplasm, n 
 Eggs, centrolecithal, 44 
 
 meiolecithal, 12 
 
 mesolecithal, 12 
 
 polylecithal, 12 
 
 tetolecithal, 12 
 Eigenmann, concerning sex cells, 404 
 
 Ejaculatory duct, 416 
 
 Embryonal bud (inner cell-mass), 64 
 
 Embryonic ccelom, 370 
 
 connective tissue, 167 
 
 disk (see also Germ disk), 134, 135 
 Embryos, abnormal, 154 
 
 age and length of, 151 
 
 conclusions of His, concerning age of, 151 
 
 gross anomalies of, 155 
 
 Mall's formula? for deducing age of, 153 
 
 normal, 154 
 
 pathological, 154 
 
 relation of age to length, 153 
 
 transparency of, 155 
 Enamel organ, 323 
 
 prisms, 324 
 
 pulp, 324 
 
 Encephalocele, 605 
 Encranius, 600 
 
 End-brain (telencephalon), 455, 467, 538 to 561 
 End disk, 14 
 
 kmob, anterior, 14, 20 
 
 posterior, 14, 20 
 
 ring, 14 
 
 Endocardium, origin of, 227 
 Endolymphatic duct, 583 
 
 sac, 583 
 
 Endomysium, 311 
 Endothelium, 217, 268 
 Engastric (intraabdominal) parasites, 601 
 Entoderm (hypoblast), 51 
 
 formation of, 51 
 
 of Amphibians, 54, 56 
 
 of Amphioxus, 51 
 
 of Birds, 58, 59, 60 
 
 of Mammals, 64 
 
 of man, 87, 90 
 
 of Reptiles, 58, 59, 60 
 
 primitive, 133 
 
 yolk, 54 
 
 Entodermal tube, 316 
 Entrance plug, 116 
 Enveloping layer, see Covering layer (tropho- 
 
 derm), 133 
 
 Eparterial bronchial ramus, 365, 368 
 Ependyma cells, 481 
 Epiblast (see also Ectoderm), 51 
 Epicanthus, 608 
 
 Epichordal brain, lateral series of nuclei of, 
 487, 488 
 
 medial series of nuclei of, 487, 488 
 Epichordal segmental brain and nerves, 457, 
 459 
 
628 
 
 INDEX 
 
 Epicondyles, 200 
 Epidermis, the, 71, 437 
 
 epitrichium of, 437 
 
 periderm of, 437 
 
 stratum corneum, 438 
 
 germinativum of, 437 
 granulosum, 437 
 lucidum, 438 
 Epididymis, anomalies of, 432 
 
 appendage of the, 416 
 
 duct of, 416 
 
 Epigamous determination of sex, 412 
 Epigenesis, doctrine of, XIII 
 Epiglottis, 361 
 Epignathus, 600, 602 
 Epimysium, 311 
 Epiphyses of vertebrae, 183 
 Epiphysis of bone, 176 
 
 (pineal body), 454, 467, 533 
 Epiploic foramen, 378 
 Epispadias, 432 
 Episternal cartilages, 185 
 Epistropheus, the (axis), 184 
 Epithalamic region, see Epithalamus 
 Epithalamus, 467, 468, 505, 536 
 Epithelium, germinal, 17 
 
 neuro-, 581, 586 
 Epitrichium, 437 
 Eponychium, the, 440 
 Epoophoron, the, 415 
 Equatorial plate, 6 
 
 Erganzungshole (see also Completion cavity), 55 
 Erganzungsplatte (see also Completion plate), 
 
 56, 59 
 
 Erythroblasts, 270 
 Erythrocytes, 270 
 Eternod's embryo, 136, 473 
 Ethmoidal labyrinth, 192 
 Eustachian tube, 590 
 Evagination, mesodermic, 73 
 Exencephaly, 605 
 Exoccipital bone, 190 
 Exoccelom, 92, 135, 
 External auditory meatus, origin of, 143, 147 
 
 ear, first appearance of, 140 
 
 form of the body, age and length of 
 
 embryos, 151 
 development of, 133 
 extremities, 149 
 branchial arches, face, neck, 145 
 
 geniculate bodies, see Geniculate bodies 
 
 genital organs (see also Genital organs, 
 external), 423 
 
 External, genitalia, first appearance of, 145 
 
 influences as affecting monsters, 612, 
 
 613 
 
 Extraembryonic body cavity, 92, 135 
 Extraventricular cell-divisions, 485 
 Extrauterine gestation, 115 
 Extremities, development of, 149 
 
 lower, fused, 611 
 
 malformations of, 610, 611 
 
 muscles of the, 303 
 
 nerve supply of, 304 
 
 one or more abnormally small but well 
 formed, 6n 
 
 one or more defective, 6n 
 
 one or more wanting, 611 
 Eye, 450, 457, 459, 460, 467, 506, 563 
 
 anomalies of, 591, 608 
 
 anterior chamber, 578 
 
 ciliary body, 577 
 
 chorioid, 575 
 
 cornea, 578 
 
 first indication of formation of, 564 
 
 formation of muscles of, 302 
 
 general development of, 563 
 
 influence on nervous system, 459 
 
 innervation of muscles of, 462 
 
 iris, 577 
 
 lens, 565 
 
 muscles of, 460 
 
 optic cup, 566, 569 
 depression, 563 
 nerve, 576 
 
 retina, 570 
 
 sclera, 575 
 
 vitreous, 575 
 Eyelashes, 578 
 Eyelids, 578 
 
 Fabricius ab Aquapendente, XIII 
 Face, development of, 145, 579 
 
 malformation of, 148, 608 
 Facial cleft, oblique, 621 
 Facialis, VII, nerve, 462, 464 
 "Faecal fistula," 113 
 Falx cerebri, 542 
 Fascia, 167 
 
 dentata, 469, 548 
 Fasciculi, see Tracts 
 Fasciculus cortico-spinal, 471 
 
 cuneatus, see Columns of Burdach 
 
 dorsal spino-cerebellar, 471 
 
 frontal cortico-pontile, 471 
 
 gracilis, see Columns of Goll 
 
INDEX 
 
 629 
 
 Fasciculus mammillo-tegmental, 537 
 
 medial longitudinal, 466, 504, 511, 516 
 
 occipital cortico-pontile, 471 
 
 retroflexus of Meynert, 538 
 
 solitarius, see Tract us solitarius 
 
 temporal cortico-pontile, 471 
 
 thalamomammillary, 537 
 
 ventral spino-cerebellar, 471 
 Fat, developing, 168 
 Feet, malformations of, 611 
 Female pronucleus, 23, 33 
 Femur, 204 
 Fenestra cochleae, 587 
 
 vestibuli (ovalis), 587 
 Fertilization, 33 
 
 factors in determining, 36 
 
 of human ovum, 37 
 
 references for further study of, 39 
 
 significance of, 38 
 Fertilized ovum, 33 
 
 amphiaster of, 33 
 
 derivation of, XIV 
 Fibers, afferent peripheral nerve, 451 
 
 afferent root, 451, 490 
 
 arcuate (external), 515 
 (internal), 508, 515 
 
 association (see also Cells, association), 
 556 
 
 connective tissue, 166 
 
 cortico pontile, see Cortico pantile fibers 
 
 cortico-spinal, see Tracts, pyramidal 
 
 efferent peripheral nerve, 452, 486 
 ventral root fibers, 486 
 
 muscle, 294 
 
 nerve, various views concerning develop- 
 ment of, 493, 494 
 
 neuroglia, 483 
 
 olivo-cerebellar, 466, 521, 529 
 
 projection (ascending and descending), 
 470, 546, 555, 559 
 
 spiral of spermatozoon, 14 
 
 visceral (splanchnic), 487, 491 
 Fibrillar connective tissue, 166 
 Fibrillogenous zone, 484 
 Fibrils, connective tissue, 166 
 Fibroblasts, 167 
 Fibula, 204 
 Filia olfactoria, 502 
 Fillet, lateral, 466, 471, 523, 530 
 
 medial, 466, 471, 520, 521, 530, 537, 
 
 557 
 
 Filum terminate, 512 
 Fimbria, 548 
 
 Fimbriae, 414 
 
 Fingers, development of, 150 
 Fissure, anterior arcuate, 540 
 calcarine, 554 
 callosal, 551 
 central, 554 
 great longitudinal, 542 
 of Rolando, 554 
 of Sylvius, 553 
 pane to-occipital, 554 
 posterior arcuate, 548 
 prima, of His, 540 
 primary, of cerebellum, 526 
 secondary, of cerebellum, 526 
 rhinal, medial and external, 540 
 ventral longitudinal, 510 
 Fissures of cerebral hemispheres, 542 
 Flechsig, concerning myelogenetic areas of 
 
 pallium, 558, 559 
 Flechsig's tract, 471, 512 
 Flemming, concerning amitosis, 4 
 Flexure, cephalic, 139 
 cervical, 140 
 dorsal, 139 
 sacral, 140 
 Flocculi, 526 
 
 Floor plate (ventral median plate), 453 
 Foetal inclusion, 600 
 membranes, 95 
 allantois, 102 
 amnion, 95 
 chorion, 103 
 earlier stages in Mammals, compared 
 
 with chick, 104 
 function of, 95 
 in Birds, 95 
 in Mammals, 103 
 in man, in 
 in Reptiles, 95 
 
 references for further study of, 132 
 serosa, 103 
 Foetus, the, 145 
 in fcetu, 600 
 papyraceus, 595 
 
 Follicle, Graafian, rupture of, 30 
 Fontanelles, 194 
 Foot, development of, 150 
 Foramen caecum linguae, 321, 331 
 of Magendie, 513 
 of Monro, 531, 539, 542, 546 
 of Winslow, 378 
 ovale, 234, 267 
 transversarium, 185 
 
630 
 
 INDEX 
 
 Foramina of Luschka, 514 
 
 Fore-brain (prosencephalon) , 454, 457, 467 
 
 anterior (cerebral) commissure, 454 
 
 chiasma eminence, 454 
 
 commissura habenularis, 455 
 
 corpora striata, 455 
 
 diencephalon, 467 
 
 epiphysis of, 454 
 
 ganglia habenulse, 455 
 
 infundibulum, 454 
 
 lamina terminalis of, 454 
 
 pallium, 455 
 
 paraphysis of, 454 
 
 pineal body, 454 
 
 processus neuroporicus, 454 ' 
 
 recessus postopticus, 454 
 praeopticus, 454 
 
 rhinencephalon, 455, 467 
 
 velum transversum, 454 
 Forel's decussation, 517 
 Formatio reticularis, 465, 511, 515 to 518 
 
 alba, 516 
 
 grisea, 516 
 Fornix, anterior pillars (columns), 476, 537, 551 
 
 body of, 551 
 
 commissure, 550 
 
 longus, 552 
 
 posterior pillar (columns) 548, 551 
 
 psalterium, 550 
 
 Forster, concerning malformations, 593 
 Fossa Sylvii, 539, 540, 552 
 Frenulum linguae, 328 
 Fretum Halleri, 231, 237 
 Frog, cleavage in, 42, 43 
 Frontal bone, 194 
 
 lobe, 542 
 Froriep, concerning acustico-facialis ganglion, 
 
 S9i 
 
 Funiculus, dorsal (posterior) or posterior white 
 column, 490, 503, 507 
 
 lateral, 511 
 
 teres, 524 
 
 ventral (anterior) or ventral white column, 
 507 
 
 ventro-lateral, 507 
 Furcula, the, 361 
 
 Galea capitis, 14, 21 
 Gall bladder, 346 
 Ganglia, cerebrospinal, 451 
 sympathetic, ciliary, 501 
 
 otic, 501 
 
 peripheral, 491 
 
 Ganglia, sympathetic, prevertebral, 491 
 sphenopalatine, 501 
 submaxillary, 501 
 vertebral, 491 
 visceral, 459, 487 
 Ganglion, acoustic, 691 
 acustico-facialis, 591 
 cochlear, 499, 591 
 Gasserian, 460, 500 
 geniculate, 498, 591 
 habenulae, 455, 533 
 interpeduncular, 538 
 nodosum, 495 
 petrosum, 495 
 Scarpa's 499, (see also Nerves, cranial, 
 
 VIII) 
 
 semilunar, 460, 500 
 spinal, 490 
 spirale, 499, 592 
 vestibular, 499, 591 
 Gartner, canals of, 416 
 
 Gasserian ganglion, peripheral branches of, 460 
 Gastral mesoderm, 73 
 Gastrointestinal tract, development of glands 
 
 in, 343 
 
 histogenesis of the, 342 
 lymph follicles of, 344 
 mucous membrane of, 342 
 Gastroschisis, 313 
 completa, 610 
 
 Gastrothoracopagus dipygus, 597 
 Gastrula, 51 
 Gastrulation, in Amphibians, 52 
 
 yolk content in, 52 
 in Amphioxus, 51 
 
 yolk content in, 51 
 in Birds, 57, 60 / 
 
 yolk content in, 57 
 in hen's egg, 60 
 in Mammals, 63 
 in man, 68, 85 
 in Reptiles,* 5 7 
 
 yolk content in, 57 
 
 in water salamander Triton taeniatus, 53 
 Geniculate bodies, lateral (external), 470, 471, 
 
 505, 533, 555, 557, 57^ 
 medial (internal), 470, 471, 537, 555 
 Geniculate ganglion, 498 
 Genital cord, 419 
 folds, 424 
 glands, the, 10 
 
 changes in the positions of, 417 
 development of the ligaments of, 417 
 
INDEX 
 
 631 
 
 Genital glands, differentiation of, 405 
 ducts of, 413 
 migration of, 419 
 stroma of, 404 
 organs, external, 423 
 first appearance of, 145 
 (female), clitoris, 424 
 glans clitoridis, 424 
 labia majora, 424 
 
 minora, 424 
 prepuce, 424 
 vestibulum vaginae, 424 ) 
 (male) penis, 424 
 prepuce, 424 
 raphe, 426 
 scrotum, 426 
 urethra, 424 
 ridge, 389, 494, 423 
 swellings, 424 
 tubercle, the, 424 
 Gennari, line of, 557 
 Genu facialis, 517 
 Germ cells, 10 
 
 female, 21 
 male, 21 
 disk, 45 
 of Birds, 45 
 of Reptiles, 60 
 hill, n, 410 
 layers, 51 
 
 diagram showing, 54 
 the ectoderm, 51 
 the entoderm, 51 
 the epiblast, 51 
 the hypoblast, 51 
 in man, 85 
 the mesoderm, 68 
 primary, 51 
 
 German method of measuring embryos, 152 
 Germinal disk (see also Germ disk), 13 
 epithelium, 404 
 cells of, 404 
 rete cords of, 404 
 sex cords of, 405 
 spot, 12 
 
 Giant glomeruli, 399 
 Gianuzzi, crescents of, 329 
 Gill arches, musculature of, 311, 459 
 Gill-cleft organs, 452 
 Gills, influence on nervous system, 459 
 Giraldes, organ of, 41 7 
 Glands, accessory thyreoid, 332 
 anterior ligual, 328 
 
 Glands, Bartholin's, 403 
 
 Brunner's, 343 
 
 bulbo-urethral, 403 
 
 carotid, 429 
 
 coccygeal, 285 
 
 Cowper's, 403 
 
 duodenal, 343 
 
 Ebner's, 322 
 
 formation of, 343 
 
 genital, 10 
 
 haemolymph, 282 
 
 indifferent (genital), 407 
 
 lacrymal, 578 
 
 lingual, 322 
 
 liver, 345 
 
 lymph, 280 
 
 mammary, 442 
 
 Meibomian, 578 
 
 of Mall, 578 
 
 parotid, 328 
 
 prehyoid, 332 
 
 salivary, 327 
 
 sebaceous, 442 
 
 sublingual, 328 
 
 submaxillary, 327 
 
 sudoriferous, 442 
 
 suprahyoid, 332 
 
 suprarenal, 426 
 
 sweat, 442 
 
 thymus, 333 
 
 thyreoid, 331 
 
 uterine, 415 
 
 vestibular, 403 
 Glans clitoridis, 424 
 
 penis, 424 
 Glia, see Neuroglia 
 Glisson, capsule of, 346, 374 
 Glomeruli of kidney, 393, 394 
 Glomus caroticum, 335, 429 
 
 coccygeum, 285 
 Glossopalatine arch, 330 
 Glossopharyngeus, IX, nerve, 462 
 Goll, column of, 459, 471, 512, 518 
 
 nuclei of columns of, 459, 466, 467, 520 
 Gonads, 10 
 Graafian follicle, 408, 409 
 
 de Graaf 's description of, XIII 
 
 primary, 407, 408 
 Graf v. Spec's ovum, 86 
 Granules, keratin, 439 
 Gray column (dorsal or posterior), 458 
 (ventral or anterior), 458, 507 
 
 matter of cord and segmental brain, 504 
 
632 
 
 INDEX 
 
 Gray ramus communicans, 492 
 
 Ground bundles of the cord, 465, 504, 507, 509, 
 
 5i6, 518 
 Growth of bones, 176 
 
 intracartilaginous, 176 
 
 long, 176 
 
 Gubernaculum testis, 418, 419 
 Gurwitsch, concerning peripheral nerves, 493 
 
 concerning the myelin sheath, 494 
 Gustatory area, 558 
 
 system, 452, 460 
 
 Gyri, transverse of temporal lobe, 557 
 Gyrus ambiens, 541 
 
 dentatus, 469, 548, 551 
 
 olfactorius lateralis, 541 
 
 semilunaris, 541 
 
 subcallosus, 552 
 
 Habenula, 533 
 Haemangiomata, 445 
 Haemoblasts, 268 
 Haemoglobin, 269, 270 
 Haemolymph glands, 282 
 Haemopoiesis, 267 
 
 views concerning, 2 7 
 monophyletic, 267 
 polyphyletic, 267 
 Hair, the, 440 
 
 anomalies of, 445 
 
 cells, 586, 588, 589 
 
 connective tissue follicle cf, 440 
 
 germs, 440 
 
 Henley's layer, 440 
 
 Huxley's layer, 440 
 
 lanugo the, 440 
 
 papilla, 440 
 
 shaft, 440 
 Hamatate, 201 
 Hammar, concerning the tuberculum impar, 
 
 321 
 Hands, development of, 150 
 
 malformations of, 611 
 Haploid number of chromosomes, 18, 22 
 Hardesty, concerning development of neuro- 
 
 glia, 479 
 
 Hare-lip, 198, 212, 608, 609 
 Harrison, concerning neurilemma cells, 493 
 Hartman, concerning cleavage, 49 
 Harvey, XIII 
 Hassall's corpuscles, 334 
 Haversian canals, 175 
 
 lamellae, 175 
 
 spaces, 175 
 
 Head, beginning of, 138 
 amniotic fold, 96 
 cap, 14 
 fold, 79 
 process (primitive intestinal cord) in the 
 
 chick, 62 
 in Mammals, 68 
 skeleton, 186 
 
 anlagen of, 187, 189 
 
 anomalies of, 211 
 
 bones derived from the branchial arches, 
 
 194 
 
 cartilage of, 187 
 
 cartilaginous primordial carnium, 188 
 chondrification of, 187 
 chondrocranium, 189 
 diagram of skull of new-born child, 193 
 membrane bones of the skull, 192 
 ossification of the chondrocranium, 190 
 periotic capsule, 189 
 table showing types of development of 
 
 bones of, 198 
 
 somatic musculature of (eye, tongue), in- 
 ner vation of, 462 
 Heart, the, 227 
 
 anomalies of, 285, 595 
 beat, 240 
 
 changes after birth, 237 
 development of, 227 
 double, 285 
 
 first indications of, 139 
 interventricular furrow, 231 
 migration of, 372, 375 
 muscle, histogenesis of, 311 
 origin of, 227 
 papillary muscles of, 237 
 septa of, 233 
 sinus venosus, 222, 232 
 valves, 236 
 Heidenhain, 9 
 Held, concerning early development of neuro- 
 
 fibrils, 484 
 Helix, 591 
 
 Hemicrania, 604, 605 
 Hemispheres, cerebral, 457, 470, 474, 538, 
 
 541 to 560 
 of cerebellum, 526 
 Henle's layers, 440 
 
 loop, 394 
 
 Hensen, concerning peripheral nerves, 494 
 Hensen's cells, 588 
 
 node, 61, 66, 87 
 Hepatic cords, 349 
 
INDEX 
 
 633 
 
 Hepatoduodenal ligament, 380 
 
 Hepatogastric ligament, 380 
 
 Heredity, important factor in teratogenesis, 612 
 
 in relation to anomalies of muscular 
 system, 314, 315 
 
 influence of, in albinism, 445 
 Hermaphroditism, 434 
 
 bilateral, 434 
 
 false, 434 
 
 feminine false, 434 
 
 lateral, 434 
 
 masculine false, 434 
 
 true, 434 
 
 unilateral, 434 
 Hernia, diaphragmatic, 382 
 
 umbilical, 113 
 Herrick, concerning the gustatory tracts, 468 
 
 concerning gustatory pathway, 519 
 Hertwig, concerning duplicity from double 
 gastrulae, 600 
 
 concerning fertilization, 38 
 
 concerning the formation of the primitive 
 streak, 61 
 
 concerning the mammary gland, 443 
 
 concerning mesoderm formation in Triton 
 and Amphioxus, 73 
 
 concerning spina bifida, 607 
 
 on production of monsters, 614 
 Heteromeric column cells, 503 
 Hind-brain (metencephalon), 455 
 Hippocampal fissure, 548 
 
 formation, 469, 543, 548, 552 
 Hippocampus major, 548, 552 
 His, concerning age and length of embryos, 151 
 
 concerning angulus praethalamicus, 540 
 
 concerning germinal cells, 479 
 
 concerning limbus corticalis and medul- 
 laris, 542 
 
 concerning neuroblasts, 485 
 
 concerning olfactory nerve, 581 
 
 concerning peripheral nerves, 494 
 
 cylinder furrow of, 509 
 
 marginal furrow of, 509 
 
 trapezoid area of, 541 
 
 Hochstetter, concerning the bucco-nasal mem- 
 brane, 579, 580 
 Holorachischisis, 605 
 Horns, anterior (ventral gray column), 458, 
 
 507 
 
 Horseshoe kidney, 429 
 Howslip's lacunae, 172 
 Huber, concerning cleavage, 50 
 Humerus, 200 
 
 Hunteri, gubernaculum, 419 
 Huxley's layer, 440 
 Hyaloid canal, 576 
 
 membrane of vitreous, 575 
 Hyaloplasm, i 
 Hydatid of Morgagni, 417 
 
 non-stalked, 414 
 Hydramnios, 112 
 Hydrencephalocele, 605 
 Hydrencephaly, 605 
 Hydrocephaly, congenital, 605 
 Hydromeningocele, 605 
 Hydromicrencephaly, 605 
 Hymen, the, 415 
 
 anomalies of, 434 
 Hyoid, 197 
 
 arch, 464 
 
 Hyperkeratosis, 444 
 Hypermastia, 445 
 Hyperthelia, 445 
 Hypertrichosis, 445 
 Hypoblast (see also Entoderm), 51 
 
 formation of, 51 
 Hypochordal bar, 184 
 Hypoglossus, XII, nerve, 462, 515 
 Hypophyseal pouch, 531 
 Hypophysis, 467, 533 
 Hypospadias, 432 
 
 Hypothalamic region, see Hypothalamus 
 Hypothalamus, 467, 468, 478, 53 1, 53^ 
 Hypotrichosis, 445 
 
 Ichthyosis, 444 
 
 Identity of chromosomes, 7, 26 
 
 Bium, the, 203 
 
 Imperforate hymen, 434 
 
 Incisive bone, 195 
 
 Incisura prima, 540 
 
 Incus, 197, 589 
 
 Indifferent glands, 407 
 
 anomalies derived from, 434 
 
 stage, diagram showing, 423 
 
 table showing structures derived from, 
 
 423 
 
 structures, 404 
 Indusium griseum, 551 
 Infracardiac ramus, 366 
 Infundibular process, 532 
 Infundibulum, 454, 478, 531 
 Inguinal ligament, 418 
 
 ring, the, 420 
 Iniencephaly, 605 
 Inner cell mass, 48, 133 
 
634 
 
 INDEX 
 
 Inner cell mass, layer of neural tube, 485, 
 
 502, 514, 527, 530, 542, 554 
 Innominate artery, 243 
 
 bone, 203 
 
 veins, 254 
 
 Insula (island of Reil), 552 
 Integumentary system, the, 437 
 
 anomalies of, 444 
 
 glands of the skin, 442 
 
 hair, 440 
 
 nails, 439 
 
 skin, 437 
 
 Inter-brain (diencephalon), see Diencephalon 
 Intercarotid ganglion, 429 
 Intercellular substance, origin of, 165 
 Intermediary plexus of lymph glands, 281 
 Intermediate areas of Flechsig, 558 
 
 cell mass, 80 
 
 (medullary) layer of telencephalon, 542 
 
 plate, 509, 511 
 
 Intermuscular connective tissue, 310 
 Internal capsule of fore-brain, 472, 537, 545, 
 546, 558 
 
 geniculate bodies, see Geniculate bodies 
 Interrenal organs, 428 
 Interventricular furrow, 231 
 Intervertebral fibrocartilage, 180, 184 
 Intervillous spaces, 127 
 Intestinal crypts of Lieberkiihn, 343 
 
 region, 317 
 
 tract, colon, 338, 340 
 duodenum, 338 
 
 mesenterial small intestine, 338 
 vermiform appendix, 341 
 
 umbilicus, 101 
 Intestine, the, 337 
 
 anomalies of, 357 
 
 crypts of Lieberkiihn, 343 
 
 loops of, 338, 339 
 
 villi of, 343 
 Iris, 577 
 
 defective pigmentation of, 445 ] 
 Ischiopagus, 596 
 
 parasiticus, 597 
 Ischiothoracopagus, 597 
 Ischium, the, 203 
 Island of Reil, 552 
 Islands of Langerhans, 354 
 Isthmus, 455, 513 
 Iter, see Aquceductus Sylvii 
 
 Jacobson's organ, 581 
 Janus asymmetros, 598 
 
 Janns, symmetros, 598 
 
 Jaws, malformations of, 608, 609 
 
 splanchnic musculature, innervation of, 
 
 462, 464 
 
 Johnston, concerning mesencephalic root of V, 
 523 
 
 concerning the optic recess, 531 
 Joint capsule, 207 
 
 cavity, 207 
 Joints, 205 
 
 diarthrosis, 207 
 
 synarthrosis, 206 
 
 synchondrosis, 206 
 
 syndesmosis, 206 
 Jugular lymph sac, 275, 278 
 
 Kallius, concerning the mammary gland, 442 
 
 Karyolysis, 270 
 
 Karyoplasm, i 
 
 Karyorrhexis, 270 
 
 Karyosomes, i 
 
 Keibel, concerning origin of endolymphatic 
 
 appendage in the chick, 583 
 Keratin granules, 439 
 Kidney, the, 391 
 
 anomalies of, 426 
 
 Bowman's capsule, 395 
 
 capsule of, 398 
 
 changes in position of, 399 
 
 columns of Bertini, 397 
 
 congenital cysts of, 430 
 
 convoluted tubule, Henle's loop of, 394 
 
 cortex of, 398 
 
 derivation of, 391 
 
 floating, 430 
 
 glomeruli of, 393 
 
 and blood vessels of, 394 
 hilus of, 397 
 
 Malpighian pyramids of, 397 
 medulla of, 398 
 metanephric blastema of, 392 
 migration of, 399 
 movable, 430 
 nephrogenic tissue of, 392 
 relation to suprarenal gland, 428 
 renal columns of, 397 
 corpuscle of, 397 
 papillae of, 393, 398 
 pelvis, 391 
 pyramids of, 397 
 tubules of, convoluted, 393 
 
 straight, 392 
 ureter, 391 
 
INDEX 
 
 635 
 
 Kidney, urinary function of, 399 
 
 Knomer, H. McE., on production of 
 
 monsters in single embryos, 614 
 Kolliker, XIV 
 
 concerning formation of incisive bone, 196 
 
 Krause, concerning origin of endolymphatic 
 
 appendage in chick and Amphibia, 
 
 583 
 Kupffer, v., concerning the acoustic ganglion, 
 
 588 
 
 concerning the differentiation of the neu- 
 ral tube, 453 
 concerning olfactory placodes, 579 
 
 Labia majora, 424 
 
 minora, 424 
 Lacrymal bone, 194 
 
 duct, 579 
 
 glands, 578 
 Lacunae, 171 
 Laloo, 597 
 Lamellae, Haversian, 175 
 
 interstitial, 175 
 Lamina affixa, 550 
 
 cribrosa (of eye), 577 
 (of nose), 192 
 
 infrachorioidea, 547, 548 
 
 lateral pterygoid, 194 
 
 medial pterygoid, 193 
 
 perpendicularis, 192 
 
 terminalis, 454, 539, 547 
 Langerhans, islands of, 354 
 Langhan's layer, 121 
 
 outgrowths from, 122 
 Lanugo, the, 440 
 Laryngeal pouch, 361, 368 
 Larynx, the, 361 
 
 anomalies of, 368 
 
 cartilages of, 362 
 
 development of, 197, 361 
 Lateral geniculate bodies, see Geniculate bodies 
 
 lemniscus, 466 
 
 line cranial nerves, 462 
 organs, 451, 452, 460, 462 
 
 nasal process, 148 
 
 plate (of mesoderm), 71 
 
 plates (of neural tube), 453 
 
 recesses of fourth ventricle, 513 
 Leg, development of, 150 
 Lemmocytes, 492 
 Lemniscus, lateral, see Fillet, lateral 
 
 medial, see Fillet, medial 
 Lens, 565 
 
 Lens, anterior epithelium of, 567 
 
 area, 565 
 
 capsule, 569 
 
 fibers of, 567 
 
 hyaloid artery of, 569 
 
 in vagina tion, 565 
 
 membrana pupillaris of, 569 
 
 tunica vasculosa of, 569 
 
 vesicle, 565 
 
 Leopold, concerning ovulation and men- 
 struation, 30 
 
 ovum of, 85 
 Leucocytes, 270 
 
 Lewis, concerning anomalies of pancreas, 358 
 Lieberkiihn, crypts of, 343 
 Life cycle, complete, in the female, 410 
 
 complete, in the male, 412 
 Ligaments, broad, of the uterus, 422 
 
 costo- vertebral, 184 
 
 diaphragmatic of the mesonephros, 418 
 
 hepatoduodenal, 380 
 
 hepatogastric, 380 
 
 inguinal, 418 
 
 middle umbilical, 115, 401 
 
 origin of fibers of, 167 
 
 ovarian, 422 
 
 round, of liver, 261 
 of uterus, 422 
 
 sphenomandibulor, 196 
 
 stylohyoid, 197 
 
 suspensory of the lens, 578 
 
 umbilical, 248 
 Ligamentum arteriosum, 240, 243, 267 
 
 coronarium hepatis, 376 
 
 suspensorium (falciforme) hepatis, 376 
 
 teres hepatis, 376 
 Limb bud, lower, 141, 149, 306 
 
 upper, 141, 149, 304 
 Limb buds, differentiation of, 304, 306 
 Limbus corticalis of His, 542 
 
 fossae ovalis, 236 
 
 medullaris, 542 
 Lingual glands, 322 
 
 papillae, 321 
 
 tonsils, 330 
 Lingula (of cerebellum), 526 
 
 (of sphenoid), 191 
 Linin, i 
 Lip, clefts of, 196, 212, 608, 609 
 
 lower, origin of, 144 
 
 upper, origin of, 144 
 Liquor amnii, 98 
 
 folliculi, 409 
 
636 
 
 INDEX 
 
 Liver, the, 345 
 
 anomalies of, 357 
 
 bile capillary of, 349 
 
 capsule of Glisson, 346 
 
 cells of, 349 
 
 circulation of, 346 
 
 ducts of, 346 
 
 gall bladder of, 346 
 
 growth of, 349 
 
 hepatic cylinders of, 347 
 
 histogenesis of, 349 
 
 lobe of Spigelius, 349 
 
 lobes of, 348 
 
 pars hepatica of, 345 
 
 cystica of, 345 
 round ligament of, 261, 349 
 vasa aberrantia of, 350 
 veins of, 260, 348 
 Lobus pyriformis, 469, 541 
 Loeb, concerning production of monsters, 614 
 Longitudinal fasciculus, medial, 466 
 Lordosis, 604 
 Lower extremities, 203 
 Lumbar enlargement, 459 
 Lunate bone, 200 
 Lung groove, 360 
 Lungs, the, 364 
 
 anomalies of, 368 
 atria of, 365 
 changes in, at birth, 367 
 ducts of, 365 
 
 eparterial bronchial ramus of, 365, 368 
 influence on nervous system, 459 
 lobes of, 365 
 weight of, 367 
 Lunula, the, 440 
 Luschka, foramina of, 514 
 Lutein cells, or granules, 31 
 Lymph, origin of, 283 
 follicles, 284 
 
 of gastrointestinal tract, 344 
 of tonsils, 330 
 glands, the, 280, 345 
 hearts, 274, 275, 278 
 sacs, 274, 275, 278 
 Lymphangiomata, 445 
 Lymphatic system, the 273 
 glands of, 280 
 glomus coccygeum, 285 
 haemophoric function of, 279 
 spleen, 283 
 thymus gland, 285 
 views concerning, 273 
 
 Lymphocytes, 270 
 
 primitive, 268, 269 
 
 Macromeres, 47 
 Macrostomus, 609 
 Macula acustica, 589 
 
 lutea, 572 
 
 Magendie, foramen of, 513 
 Magma-re ticulare, 155 
 Male pronucleus, 23, 33 
 Malformation involving one individual (see 
 
 Monsters), 604 
 Malformations of more than one individual (see 
 
 Duplicate monsters), 593 
 Mall, concerning development of the maxilla, 
 
 195 
 
 concerning development of pyramids, 555 
 concerning ossification of incisive bone, 195 
 formulae for estimating age of embryos, 153 
 on faulty implantation of the ovum, 613 
 on theories of production of monsters, 612 
 Malleus, 197, 589 
 Malpighian corpuscle, 387 
 
 pyramids, 397 
 Mammary gland, the, 442 
 anomalies of, 445 
 areolar glands of, 443 
 colostrum corpuscles, 444 
 growth of, in female, 443 
 growth of, in male, 443 
 nipple, 443 
 of pregnancy, 443 
 Mammillary bodies, 533 
 
 region, 478, 533 
 Mandible, 196 
 
 Mandibular process, 140, 147, 318 
 Mantle fibers, 6 
 
 layer of neural tube, 485, 502, 514, 527, 
 
 530, 542, 554 
 Manubrium sterni, 186 
 
 Marchand's fusion theory of symmetrical 
 duplicity, 599 
 
 scheme of duplicate monsters, 593 
 Marginal furrow of His, 509 
 
 layer of neural tube, 479, 514, 527, 530, 542 
 Mark and Long, concerning maturation, 22 
 Marrow, 177 
 
 cavity, primary, 173 
 
 formation of blood cells in, 271 
 
 red, 178 
 
 spaces, primary, 171 
 
 yellow, 178 
 Marsupials, early nutritional conditions in, 108 
 
INDEX 
 
 637 
 
 Masculine false hermaphroditism, 434 
 Massa intermedia, 535 
 Mastoid process, 191 
 Maternal impressions, 612 
 Maturation, 17 
 
 and mitosis, significance of, 25 
 
 in Ascaris, 17 
 
 of the ovum, 21 
 
 of the sperm, 17 
 
 references for further study of, 32 
 Maxilla bone, 194 
 Maxillary process, 140, 147, 318 
 McMurrich, concerning derivation of the 
 dermis, 438 
 
 concerning umbilical cord, 129 
 Mechanical theory of monsters, 613 
 Meckel's cartilage, 189, 194, 196 
 
 diverticulum, 113, 339 
 Medial fillet, see Fillet, medial 
 
 geniculate bodies, see Geniculate bodies 
 
 lemniscus, see Fillet, medial 
 
 longitudinal fasciculus, 466, 504, 511, 516, 
 
 5i7 
 
 nasal process, 148 
 Mediastinum testis, 413 
 Medulla oblongata, 477, 512 
 
 taenia of, 513 
 Medullary cords, 406, 407 
 
 folds, in chick blastoderm, 63 
 
 groove, 67 
 
 layer of telencephalon, 542, 554 
 
 sheath, see Myelin sheath 
 Megakaryocytes, 273 
 Megaloblasts, 272 
 Meibomian glands, 578 
 Meiolecithal ova, 12 
 Meissner, plexus of, 491 
 
 tactile corpuscles of, 438 
 Membrana preformativa, 325 
 
 tectoria, 588 
 
 undulatoria, 15 
 
 Membrane bones of the skull, 192 
 Mendel's law of segregation, 26 
 Meningocele, 605 
 Meningoencephalocele, 605 
 Menstruation, 29 
 
 relation to fertilization, 29 
 
 relation to ovulation, 29 
 Merocytes, 59 
 Merorachischisis, 606 
 Mesencephalon (mid-brain), 84, 454, 475 
 Mesenchyme, 165 
 Mesenterial small intestine, 338 
 
 Mesenteries, 370, 377, 380 
 
 anomalies of, 382 
 Mesentery of the jejunum, 380 
 Mesoappendix, 381 
 Mesocardium, dorsal, 227, 372 
 
 ventral, 227, 372 
 Mesocolon, ascending, 381 
 descending, 381 
 sigmoid, 381 
 transverse, 380 
 
 Mesoderm, derivatives from, 161 
 development of, 134 
 extraembryonic, 88 
 
 origin of, 90 
 
 formation in Amphibians, 72 
 in Amphioxus, 68 
 in Birds, 75 
 in the frog, 73 
 in Mammals, 81 
 in man, 86, 88, 91, 92 
 in Reptiles, 74 
 gastral, 73 
 intraembryonic, 88 
 
 origin of, 91 
 
 layers of, in von Spec's embryo, 88 
 parietal, 71, 134 
 peripheral, 83 
 origin of, 91 
 peristomal, 54, 73 
 splanchnic, 102, 342 
 visceral, 71, 83, 134 
 Mesodermic evagination, 73 
 
 somites, 68, 139, 293, 300 
 Mesoduodenum, 380 
 Mesogastrium, dorsal, 335, 377 
 
 ventral, 336, 377 
 Mesolecithal ova, 1 2 
 Mesonephric duct, 386 
 mesentery, 418 
 ridge, 385, 388 
 Mesonephroi, atrophy of, in the female, 415 
 
 in the male, 416 
 Mesonephros, 386 
 
 Bowman's capsule, 387 
 degeneration of, 390 
 diaphragmatic ligament of, 389, 418 
 disappearance of, 390 
 function of, 389 
 glomerulus of, 387 
 Malpighian corpuscle of, 387 
 renal portal system of, 390 
 significance of, 390 
 tubules of, 386 
 
638 
 
 INDEX 
 
 Mesorchium, 406, 419 
 
 Mesorectum, 381 
 
 Mesosalpinx, 416, 422 
 
 Mesothelium, 370, 423 
 
 Mesovarium, 406, 419, 422 
 
 Metacarpals, 201 
 
 Metanephric blastema, 392 
 
 Metanephros, see Kidney 
 
 Metaphase, 6 
 
 Metaplasm, i, 2 
 
 Metaplexus, 513 
 
 Metapore, 513 
 
 Metatarsals, 205 
 
 Metathalamic portion of thalamus, 536, 546 
 
 Metathalamus, see Metathalamic portion of 
 
 thalamus 
 Metazoa, 10 
 
 Metencephalon (hind-brain), 84, 455 
 Method of measuring embryos, American, 153 
 
 German, 152 
 Metopic suture, 194, 212 
 Metopism, 212 
 Meyer, concerning mesencephalic root of V, 5 23 
 
 Adolf, concerning segments of segmental 
 
 brain and cord, 505, 506 
 concerning suprasegmental and segmen- 
 tal structures, 450, 457 
 Meynert, solitary cells of, 558 
 Meynert's decussation, 530 
 Micrencephaly, 605 
 Microbrachius, 611 
 Microcephaly, 605 
 Micrognathus, 356, 609 
 Micrognathy, 356, 609 
 Micromelus, 611 
 Micromeres, 47 
 Microphthalmia, 591, 608 
 Micropus, 611 
 Micropyle, 36 
 Microstomus, 609 
 Mid-body, 8 
 Mid-brain (mesencephalon), 454, 475 
 
 optic lobes, 455 
 
 roof, 457, 467 
 
 descending tracts to after-brain and cord 
 
 segments, 467 
 Middle peduncle of cerebellum, 466, 471, 473, 
 
 523, 530 
 
 Milk ridge, the, 442 
 teeth, 323, 326 
 
 Mimetic musculature and its innervation, 464 
 Minot, concerning foetal membranes of um- 
 bilical cord, 129 
 
 Mitoses (see also Cell proliferation and Gemi- 
 nal cells], 479, 514, 519, 536 
 
 extraventricular, 485 
 
 of neural tube cells, 479, 530 
 Mitosis, 4 
 
 and maturation, significance of, 25 
 
 diagrams of successive stages of, 5, 7 
 
 of mucous cells of stomach, 344 
 
 multipolar, 9 
 
 phases of, 4 
 
 pluripolar, 9 
 Mitotic division of sex cells, 404 
 
 figure, 6 
 
 Mitral cells, 505 
 Monaster, 6 
 Monobrachius, 6n 
 Monochorionic quadruplets, 599 
 
 triplets, 599 
 
 twins (equal), 594, 595 
 
 (unequal), 595 
 
 Mononuclear leucocytes, 270 
 Monopolar cells, 485 
 Monopus, 611 
 Monotremes, early nutritional conditions in, 
 
 1 08 
 
 Monro, foramen of, 531, 539, 542, 546 
 Monsters, amniotic adhesions, 611 
 
 causes underlying origin of, 612 
 
 defects in region of face and neck, and 
 their origin, 609 
 
 defects in region of neural tube, 604 
 origin of, 607 
 
 defects in the thoracic and abdominal 
 
 regions, and their origin, 610 
 in single embryos, 614 
 
 malformations of extremities, 610 
 polysomatous, 613 
 
 production of duplicate, 613 
 Montgomery, concerning areolar glands, 443 
 Morgagni, hydatid of, 417 
 
 concerning development of blastomeres, 
 610 
 
 concerning production of spina bifida, 614 
 
 liquor, 567 
 
 non-stalked hydatid of. 414 
 Morula, 40, 46, 48, 133 
 Mossy fibers, 530 
 Motor cortex (see also Pallittm, torecentral area 
 
 of], 558 
 Mouth, the, 317 
 
 angle of the, 141, 148, 318 
 
 anomalies of, 356 
 
 development of, 319 
 
INDEX 
 
 639 
 
 Mouth, influence on nervous system, 459 
 origin of, 317 
 slit, 148 
 
 Mucous tissue, 129 
 Mullerian ducts, 399, 413 
 
 atrophy of, 417 
 Multiple placentae, no 
 Multiplicity, 597 
 Muscle fibers, change of direction of, 295 
 
 theories concerning internal structure of, 
 
 308 
 
 heart, histogenesis of, 311 
 plates, 164, 294 
 
 formation from primitive segment, 71 
 tissue, histogenesis of striated volun- 
 tary, 307 
 smooth, 311 
 
 Muscles, branchiomeric, 302 
 differentiation of, 305 
 extrinsic, of the upper extremity, 
 anomalies of, 314 
 lattissimus dorsi, 305 
 levator scapulae, 305 
 pectoralis, 305 
 serratus, 305 
 trapezius, 305 
 innervation of, 294 
 of the extremities, 303 
 derivation of, 303 
 derivation from premuscle sheath of 
 
 muscles of lower extremity, 306 
 differentiation from mesenchymal tis- 
 sue, 304 
 
 extrinsic muscles, 305 
 migration of, 306 
 of the head, 300 
 chondroglossus, 303 
 
 constrictor muscles of the pharynx, 303 
 development and innervation of, 302 
 digastricus, 302, 303 
 epicranius, 303 
 glossopalatinus, 303 
 laryngeal, 303 
 masseter, 302 
 mentalis, 303 
 
 muscles of the soft palate, 303 
 mylohyoideus, 302 
 obliquus inferior, 302 
 
 superior, 302 
 platysma, 303 
 
 quadratus labii superioris, 303 
 recti inferior, 302 
 medialis, 302 
 
 Muscles of the head, recti superior, 302 
 rectus lateralis, 302 
 pterygoidei, 302 
 risorius, 303 
 stapedius, 303 
 sternomastoideus, 303 
 stylohyoideus, 303 
 stylo-pharyngeus, 303 
 temporalis, 302 
 tensor tympani, 302 
 veil palatini, 302 
 trapezius, 303 
 triangularis, 303 
 of the trunk, 295 
 coccygeus, 300 
 geniohyoideus, 299 
 intercostales, 298 
 levator ani, 300 
 longus capitis, 298 
 longus colli, 298 
 olbiqui abdominis, 298 
 omohyoideus, 299 
 perineal, 300 
 psoas, 298 
 pyramidalis, 299 
 quadratus lumborum, 298 
 rectus abdominis, 299 
 capitis anterior, 298 
 sacrospinal, 300 
 scaleni, 298 
 
 sphincter ani externus, 300 
 sternohyoideus, 299 
 sternothyreoideus, 299 
 transversus abdominis, 298 
 
 thoracis, 298 
 
 Muscular system, the, 293 
 amomalies of, 313 
 skeletal musculature, 293 
 visceral musculature, 293, 311 
 Musculature, hyoid, 302 
 skeletal, 293 
 
 diaphragm, the, 300 
 early character of, 293 
 loss of segmental character, 294, 295 
 muscles of the extremities, 303 
 of the head, 300 
 of the trunk, 295 
 myotomic origin, 293, 300, 303 
 visceral, 311 
 
 mesodermic origin of, 311 
 Myelencephalon (after-brain), 84, 455, 512 
 Myelin sheath, 478, 494 
 Myeloblasts, 177, 272 
 
640 
 
 INDEX 
 
 Myelocystocele, 606 
 
 Myelocytes, 177, 272 
 
 Myelogenetic fields (areas) of Flechsig, 
 
 558 
 
 Myelomeningocele, 606 
 Myeloplaxes, 177, 272 
 Myelospongium, 479, 483 
 Myoblasts, 303, 307 
 Myocardium, 228, 311 
 Myoccel (coelom), 71, 370 
 Myotomes, 163, 294 
 
 alternation of, with vertebrae, 180, 
 
 295 
 
 change of direction in fibers of, 295 
 degeneration of, 295 
 differentiation of, 295 
 fusion of, 295, 314 
 longitudinal splitting of, 295, 314 
 migration of, 295, 314 
 tangential splitting of, 295, 314 
 
 Naevi pigmentosi, 445 
 Nail groove, 439 
 
 wall, 439 
 Nails, the, 439 
 
 epitrichium of, 440 
 
 eponychium of, 440 
 
 lunula of, 440 
 
 migration of, 439 
 
 replacement of, 440 
 Nanocephaly, 605 
 Nares, outer, 580 
 
 posterior, 580 
 Nasal bone, 194 
 
 conchae, 580 
 
 fossae, 140, 589 
 
 pit, 148, 319, 589 
 
 process, lateral, 148 
 medial, 148 
 
 sacs, 589 
 
 septum, 192, 319 
 Naso-f rental process, 147, 317 
 Naso-optic furrow, 142, 147, 579 
 Navicular bone, 200 
 Neck, development of, 145 
 Neck-rump length of embryos, 153 
 Neopallial commissure (see also Corpus cal- 
 
 losum), 468 
 Neopallium, 467, 468, 472, 552 to 560 
 
 centrifugal connection (see also Tracts, 
 pyramidal, Cortico-pontile fibers and 
 Fibers, projection descending), 471, 472, 
 546, 555, 558 
 
 Neopallium, centripetal connections (see also 
 Fillets, Thalamic radiations and Fibers, 
 projection ascending), 470, 471, 537, 
 546, 555, 558 
 Nephrogenic tissue, 392 
 Nephrostomes, 386 
 Nephrotomes, 388 
 Nerve fibers, afferent peripheral, 451, 486 
 
 efferent peripheral, 452 
 Nerves, cranial, abducens, VI, 462, 515 
 
 nucleus and roots of, 488, 515, 517, 524 
 acoustic (auditory) VIII, 462, 465, 499, 
 
 Soo, 503, 518, 588 
 cochlear ganglion, 499, 588 
 
 part, 462, 465 
 cochlear root, 500, 588 
 vestibular ganglion, 499, 588 
 
 part, 462, 465 
 
 vestibular root, 500, 503, 518, 588 
 facialis, VII, 462, 464 
 
 afferent roots, solitary tract, 499, 518 
 chorda tympani, 498 
 efferent nucleus and roots of, 488, 517 
 geniculate ganglion of, 498, 588 
 glossopharyngeus, IX, 462, 464 
 afferent part of, 462 
 
 roots, 499 
 
 efferent nucleus and efferent root of, 488 
 ganglion of the trunk (petrosum), 495 
 
 of the root, 495 
 
 lingual and tympanic branches of, 498 
 great superficial petrosal branch, 498 
 hypoglossus, XII, 462, 515 
 
 nucleus and roots of, 468, 524 
 lateral line, 462 
 olfactory, I, 467, 501, 505 
 
 terminal nuclei, or mitral cells of the 
 
 olfactory bulb, 505 
 optic, II, 454, 467, 505, 530, 576 
 
 ganglion cells of, 505 
 oculomotor, III, 462 
 
 nucleus and roots of, 488 
 somatic, 462 to 466 
 spinal accessory, XI, 464, 495 
 efferent fibers of, 496 
 
 nuclei and roots of, 488 
 splanchnic, 460 to 465 
 trigeminus, V, 460, 462, 464 
 
 afferent root (portion major), and spinal, 
 
 V, 460, 501, 503, 518 
 efferent nuclei and roots of, 488 
 Gasserian or semilunar ganglion, 460, 
 500 
 
INDEX 
 
 641 
 
 Nerves, trigeminus, mandibular branch, 500 
 maxillary branch, 500 
 mesencephalic root of, 523 
 opthalmic branch, 500 
 trochlear, IV, 462 
 
 nucleus and roots of, 488 
 vagus, X, 462, 464 
 afferent roots, 499 
 efferent fibers of, 496 
 
 nuclei and roots of, 488, 518 
 ganglia of root, 495 
 ganglion of trunk (nodosum), 495 
 Nerves, spinal, peripheral, dorsal branch of, 487, 
 
 490 
 
 ventral branch, 487, 490 
 Nervous system, the 447 
 anomalies of, 560 
 anterior neuropore, 451 
 brain, 453 
 central distinguished from peripheral, 
 
 449 
 
 cerebrospinal ganglia, 45 1 
 components of , afferent and efferent, 447 
 derivation of, 451 
 epichordal segmental brain and nerves, 
 
 459 
 
 general considerations of, 447, 448 
 human, 489 
 nerve fibers, 451 
 neural crest, 451 
 
 folds, 451 
 
 groove, 451 
 
 plate, 451 
 
 tube, 451 
 
 primitive nervous mechanism, 448 
 root fibers of, 451 
 spinal cord and nerves, 453, 457 
 three-neurone reflex arc, 450 
 two-neurone reflex arc, 448 
 vertebrate, 450 
 central, 449 
 
 supraseg mental structures of, 450, 457 
 human, afferent peripheral and sym- 
 
 pathetic neurones, 489 
 anomalies of, 560 
 cell proliferation of, 479 
 cerebellum, 455, 457, 466, 512, 525 
 corpora quadrigemina, 467, 517, 530 
 development of the lower (interseg- 
 
 mental) intermediate neurones, 502 
 differentiation of peripheral neurones of 
 
 cord and epichordal segmental brain, 
 
 486 
 
 Nervous system, human, early differentiation 
 
 of nerve elements, 483 
 epicordal segmental brain, 512 
 epithelial stage of, 479 
 further differentiation of neural tube, 
 
 506 
 general development of, during first 
 
 month, 472 
 histogenesis of, 478 
 spinal cord, 506 
 peripheral, 447 
 effectors of, 448 
 receptors of, 448 
 sympathetic, 458 
 
 efferent peripheral visceral neurones of, 
 
 45i 
 
 vertebrate, bilateral character of, 450 
 cephalization, 450 
 general features compared with human, 
 
 457 
 
 general plan of, 450 
 
 segmentation of, 450 
 
 typical, 450 
 Net knots, i 
 Neural crest, 75, 451, 490 
 
 relation to cerebrospinal ganglia, 451 
 
 segmentation of, 451 
 
 separation of, 451 
 folds, 69, 451, 472 
 
 fusion of, 451, 472 
 
 groove, 69, 73, 74, 80, 85, 87, 135, 451, 472 
 plate, 77, 451, 472 
 
 differentiation of, 453 
 tube, 70, 80, 451, 472 
 
 alar plate, 477, 512, 515, 519 
 
 basal plate, 477, 512, 514 
 
 blood vessels of, 508 
 
 cells of, 479, 481, 483, 484 
 
 cervical flexure, 478 
 
 defects in the region of, 607 
 
 floor plate of, 453, 473 
 
 further differentiation of, 506 
 
 lateral plates of, 453, 473 
 
 layers of, 479, 485, 514 
 
 limiting membranes of, 479 
 
 neuromeres, 456, 477 
 
 order of development of, 478, 506, 515, 
 
 5i9, 542 
 
 origin of malformations of, 607 
 
 roof plate of, 453, 473, 513 
 
 sulcus limitans, 477, 512 
 Neurenteric canal, 70, 317 
 Neurilemma, 478, 492 
 
642 
 
 INDEX 
 
 Neurilemma, cells of, 492 
 Neuroblasts of His, 485 
 Neuro-epithelium, 581, 586 
 Neurofibrils, 478, 484, 489 
 Neuroglia cells, 481, 485 
 
 fibers, 483 
 
 Neuromeres, 456, 477 
 Neurone layer, see Mantle layer 
 Neurones, afferent peripheral, 447, 457, 489 to 
 502 
 
 afferent versus efferent, 457 
 
 association, 457, 468, 528, 530, 558 
 
 central, 449 
 
 differentiation of, 478 
 
 distal (first) optic, 576 
 
 efferent peripheral, 447, 457, 486 to 489 
 
 intermediate, 449, 459, 502 
 
 intersegmental (see also Ground bun- 
 dles and Formatio reticularis) , 459, 
 465, 478, 502, to 506, 515 
 of epichordal segmental brain, 465 
 to suprasegmental structures, 459 
 
 intersegmental, of epichordal brain, 515 
 to 518 
 
 middle (second) optic, 576 
 
 somatic efferent, 459 
 
 splanchnic efferent, 459 
 
 suprasegmental, 478 
 Neuropore, 70 
 
 anterior, 451, 473 
 Nipple, the, 443 
 Nodule of cerebellum, 526 
 Normal embryos, 154 
 Normoblasts, 270 
 Nose, 450, 457, 505, 582 
 
 anomalies of, 212, 608 
 
 bucco-nasal membrane, 580 
 
 Jacobson's organ, 581 
 
 nasal conchae, 580 
 
 origin of, 144, 579 
 
 primitive choanen, 580 
 palate, 580 
 
 sinuses of, 580 
 Notochord, 68, 178 
 Nuck, diverticulum of, 422 
 Nuclear groups, 1 23 
 
 layer of neural tube, 479 
 
 membrane of typical cell, i 
 
 reticulum of typical cell, i 
 Nuclei, lateral, 466 
 
 of columns of Burdach, 459, 466, 471, 520 
 
 of columns of Goll, 459, 466, 471, 520 
 
 of thalamus, 537 
 
 Nuclei, pontile, 466, 519, 530 
 
 receptive, 467 
 
 red (ruber), 466, 517 
 
 terminal of afferent nerves of epichordal 
 
 brain, 518 to 525 
 of tractus solitarius, 462, 519, ^24 
 of V, 460, 520, 523, 524 
 of VIII, 462, 522 
 
 tracts from Deiter's, 466, 511 
 Nucleoli, function of, 2 
 
 false, i 
 
 true, 2 
 
 Nucleoplasm, i 
 Nucleus, the, i 
 
 ambiguous, X, 488, 517 
 
 caudatus of corpus striatum, 546 
 
 commissuralis, 519 
 
 dentatus, 471, 472, 530 
 
 diffuse, 2 
 
 dorsal efferent, X, 488 
 
 functions of, 2 
 
 habenulae, 455, 533 
 
 incertus, 524 
 
 inferior olivary, 466, 519, 520, 524 
 
 intercalatus, 524 
 
 lateral, 520 
 
 lenticularis, 546 
 
 lentiformis, 546 
 
 of Darkschewitsch, 517 
 
 structure of, i 
 Nutrition of earliest stages of embryo, 104 
 
 Obex, 513 
 
 Obturator foramen, 203 
 
 Occipital bone, 190, 192 
 
 depression, 142 
 Occulomotor, III, nerve, 462 
 Odontoblasts, 325 
 Odontoid process (dens), 184 
 (Esophageal region, 317 
 (Esophagus, the, 335 
 
 anomalies of, 356 
 Olfactory apparatus, see Nose 
 
 area (see also Archipallium) , 558 
 
 bulbs, 452, 541 
 
 lobes, 469, 478, 540, 541 
 
 anterior, 469, 539, 540, 541, 579 
 posterior, 469, 539, 540, 54i> 579 
 
 I, nerve, 467, 468, 501, 55 
 
 peduncle, 541 
 
 placodes, 579 
 
 stalk, 541 
 
 tracts, 467, 468, 505, 537 
 
INDEX 
 
 643 
 
 Olives, accessory, 520 
 
 inferior, 466, 519, 520, 524 
 
 superior, 523 
 
 Olivo-cerebellar fibers, 521, 529 
 Oraenta, anomalies of, 382 
 Omental bursa, 378 
 
 epiploic foramen of, 378 
 Omentum, 377 
 
 greater, 378 
 
 lesser, 379 
 Omosternum, 211 
 Omphalocele, 610 
 Omphalomesenteric arteries, 101, 103, 218, 246 
 
 veins, 102, 218 
 Oocyte, primary, 21, 22, 24 
 
 secondary, 22, 24 
 Oogonia, 22, 24 
 Opercula of insula, 552, 553 
 Optic apparatus, see Eye 
 
 chiasma, 505, 531 
 
 cup, 566, 469, 577 
 
 depression, 563 
 
 evagination, 564, 576 
 
 lobes, 455, 467, 468 
 
 II, nerve, 454, 467, 5Q5, 53, 57$ 
 
 neurone, first or distal, 573 
 second or middle, 573 
 
 radiation, 470, 471 
 
 stalk, 564, 576 
 
 thalami, 576 
 
 tract, 468, 505, 530, 576 
 
 vesicle area, 564 
 
 vesicles, 140, 454, 474, 564 
 Ora serrata, 570 
 Oral fossa, 139, 147 
 
 pit, 318 
 
 Orbitosphenoid bone, 191 
 Organ of Corti, 460, 467, 558, 587 
 
 of Giraldes, 417 
 
 of Rosenmiiller, 415 
 Organogenesis, 159 
 Os calcis (calcaneus), 204 
 
 centrale, 213 
 
 coxae, 203 
 
 Ossa suprasternalia, 185 
 Osseous tissue, 169 
 Ossification center, 171, 174 
 
 endochondral, 172 
 
 intracartilaginous, 172 
 
 intramembranous, 169 
 
 subperiosteal, 172, 174 
 
 stage, 182 
 Osteoblasts, 171, 273 
 
 Osteoclasts, 171, 177, 273 
 Osteogenetic tissue, 171, 173 
 Ostium abdominale tubae, 414 
 Otic ganglion, 501 
 Otocyst, 582 
 Ova, centrolecithal, 44 
 
 classification of, 12 
 
 meiolecithal, 12 
 
 mesolecithal, 12 
 
 polylecithal, 12 
 
 primitive, 408 
 number of, 410 
 
 telolecithal, 12 
 Ovarian cysts, 602 
 
 (Graafian) follicle, 409 
 liquor folliculi, 409 
 rupture of, 410 
 stratum granulosum of, 409 
 
 zona pellucida, 409 
 
 radiata, 409 
 
 Ovarian ligament, the, 422 
 Ovary, the, 10 
 
 anomalies of, 433 
 
 corpus hsemorrhagicum, 411 
 luteum, 410 
 
 descent of, 422, 437 
 
 diverticulum of Nuck, 422 
 
 egg nests, 408 
 
 ligaments of, 422 
 
 medullary cords of, 406, 407 
 
 migration of, 417, 422 
 
 Mullerian duct of, 413 
 
 parasitic growths of, 601 
 
 Pfliiger's egg cords of, 408 
 
 primary Graafian follicle of, 408 
 
 rete of, 407 
 
 stratum greminativum, 407 
 
 theca folliculi, 409 
 Oviduct, 414 
 
 anomalies of, 433 
 
 fimbriae, 414 
 
 non-stalked hydatid of Morgagni, 414 
 
 ostium abdominale tubae of, 414 
 Ovists, XIII 
 Ovium, 10 
 Ovulation, 29, 30 
 Ovum, the, 10, 409 
 
 Bryce and Teachers, 86, 90, 92 
 
 containing two originally distinct anlagen, 
 
 599 
 
 faulty implantation of, 615 
 fertilization of, 33 
 of human, 37 
 
644 
 
 INDEX 
 
 Ovum, fixation to uterus, 116 
 Graf Spec's, 86, 154 
 Leopold's 85, 154 
 maturation of, 21 
 Peters', 86, 154 
 size of, 10 
 
 Palate, the, 319 
 
 bone, 194 
 
 cleft, 212, 608, 609 
 
 primitive, 580 
 Palatine processes, 319 
 Pallium, 455, 467, 474, 538, 539, 541 to 560 
 
 archipallium, 468, 505, 537, 541, 546 to 
 552 
 
 association neurones of, 468, 528, 530, 558 
 
 calcarine area or region (see also Visual 
 area}, 557, 558 
 
 corpora striata, 455, 46^ 54* 
 
 cortex of, 554 
 
 development of, 468 
 
 hemispheres of, 457, 470, 474, 538, 541 
 to 560 
 
 layer of giant pyramid cells, 558 
 
 layers of, 557 
 
 neopallium, 450, 552 to 560 
 
 postcentral area of, 471, 555, 557, 558 
 
 precentral area of, 472, 557, 558 
 
 rhinencephalon, 455, 467, 540 
 Pancreas, the, 350 
 
 anomalies of, 358 
 
 cells of, 354 
 
 connective tissue of, 352 
 
 duct of Santorini of, 351, 358 
 of Wirsung of, 351, 358 
 
 histogenesis of, 353 
 
 islands of Langerhans, 354 
 Pander, XIII 
 Papillae, filiform, 321 
 
 fungiform, 321 
 
 hair, 440 
 
 lingual, 321 
 
 nerve, 438 
 
 renal, 396, 398 
 
 vascular, 438 
 Papillares muscle, 237 
 Paradidymis, the, 414 
 Paraphysis, 454, 534 
 Paraplasm, i 
 Parasitic duplicity, 600 
 
 origin of, 602 
 
 Parasitic structures in the sexual glands, 601 
 Parathyreoids, 332 
 
 Parietal bones, 194 
 
 cavity, 227 
 of His, 372 
 
 mesoderm, 71, 83, 134, 370 
 
 recess, dorsal, of His, 372 
 Parolfactory area of G. Elliot Smith (see also 
 
 Preterminal area), 469, 541 
 Paroophoron, the, 416 
 Parovarium, the, 415 
 Pars basilaris, 190 
 
 ciliaris retinae, 577 
 
 cystica, 345 
 
 hepatica, 345 
 
 mastoidea, 191 
 
 optica retinae, 577 
 
 petrosa, 191 
 
 squamosa, 190 
 
 subthalamica, see Hypolhalamus 
 Partes laterales, 190 
 Patella, the, 204 
 Pathological embryos, 154 
 Paton, concerning development of pyramids, 
 
 555 
 
 concerning peripheral nerves, 494 
 Peduncles of cerebellum, middle, 466, 471, 473, 
 
 523, 530 
 
 inferior cerebellar, see Resliform body 
 
 superior, 466, 471, 473, 530 
 Pellicle of cytoplasm, 168 
 Pelvic girdle, 203 
 Penis, the, 424 
 
 supernumerary, 601 
 Perforated space, posterior, 533 
 Perforatorium, 14 
 Pericardial cavity, primitive, 84 
 Pericardium, the, 370, 377 
 
 anomalies of, 382 
 Perichondrium, 173 
 Periderm, the, 437 
 Perilymph, 586 
 Perilymphatic space, 586 
 Perimysium, 311 
 Perineal body, the, 424 
 Perobrachius, 611 
 Perichordal sheath, 186 
 Periosteal buds, 173 
 Periosteum, 171 
 Periotic capsule, 189 
 Peripheral nervous system, see Nervous 
 
 system, peripheral 
 Peristomal mesoderm, 54, 73 
 Peritoneum, 382 
 Peritonsillar fissure, 526 
 
INDEX 
 
 645 
 
 Perivitelline space, n 
 
 Permanent teeth, 327 
 
 Peromelus, 611 
 
 Peropus, 611 
 
 Persistence of the cloaca, 357 
 
 Pes pedunculi, 466, 471, 523, 524, 558 
 
 Peter, concerning nasal sac, 579, 580 
 
 concerning origin of endolymphatic appen- 
 dage in Amphibia, 583 
 Peters' ovum, 86, in, 135 
 Peyer's patches, 344 
 Pfluger's egg cords, 408 
 Phaeochrome cells, 426 
 
 granules, 426 
 Phaeochromoblasts, 427 
 Phalanges, 201 
 Pharyngeal membrane, 318, 330 
 
 region, 317 
 
 tonsils, 330 
 
 Pharyngopalatine arch, 330 
 Pharynx, the, 329 
 
 anomalies of, 356 
 
 development of, 329 
 
 glossopalatine arch, 330 
 
 pharyngopalatine arch, 330 
 
 pillars of the fauces, 330 
 Physico-chemical theory of monsters, 613 
 Piersol, classification of malformations of the 
 
 extremities, 610 
 Pigment, 438 
 
 of neurones, 478, 489 
 Pillars of the fauces, 330 
 Pineal body, 454, 467, 533 
 
 stalk, 533 
 Pisiform, 201 
 
 Pituitary body, irregular tumors of, 600 
 Placenta, no 
 
 anomalies of, 130 
 
 annular, 130 
 
 attachment of, to ovum and to uterine 
 wall, 128 
 
 bipartita, 130 
 
 blood vessels of, 127 
 
 chorion frondosum, 118, 120 
 
 decidua basalis, 118, 120 
 
 discoidal, no 
 
 duplex, 131 
 
 expulsion of, 130 
 
 fcetalis, no 
 
 functions of, 124 
 
 maternal, no 
 
 membranacea, 130 
 
 praevia, 128 
 
 Placenta, relations of, to uterine mucosa, 1 10, 1 20 
 
 size of, 128 
 
 spuria, 131 
 
 succenturiata, 131 
 
 uterina, no 
 
 zonular, no 
 Placenta?, multiple, no 
 Placental septa, 123 
 Placentalia, no 
 Placodes, 452, 495, 505 
 
 auditory, 582 
 
 epibranchial, 452 
 
 olfactory, 579 
 
 suprabranchial, 452 
 Plagiocephaly, 212 
 Plasmodi-trophoderm, 117, 121, 122 
 Plasmosomes, 2 
 Plastids, 2 
 Pleura, the, 366, 377 
 Pleural cavities, 373 
 Pleuroperitoneal membranes, 375 
 Pleuroperitoneum, 370 
 Plexus, Auerbach's, 491 
 
 chorioideus, see Chorioid plexus 
 
 Meissner's, 491 
 
 vitelline, 217 
 Plica arcuata, 548 
 
 chorioidea (fold), 547 
 
 encephali ventralis, 453 
 
 rhombo-mesencephalica, 475 
 
 semilunaris, 579 
 Plicae palmatae, 415 
 Polar bodies, 21, 22, 25 
 
 differentiation, 12 
 
 relation to production of monsters, 603 
 
 rays, 6 
 
 Polydactyly, 213, 6n 
 Polykaryocytes, 177, 273 
 Polylecithal ova, 12 
 Polysomatous monsters, 613 
 Polyspermy, 36 
 Pons varolii, 475, 523 
 Pontile nuclei, 466, 519, 523, 530 
 Pontine flexure, 477 
 Porencephaly, 605 
 Portio major, 501 
 
 Postbranchial branches of nerves, 464 
 Posterior arcuate fissure, 548 
 
 colliculi, see Posterior corpora quadrigemina 
 
 corpora quadrigemina, 467, 517, 530 
 horn (dorsal gray column), 508 
 longitudinal fasciculus, see Fasciculus, 
 medial longitudinal 
 
646 
 
 INDEX 
 
 Posterior nares, 320 
 Prebranchial branches of nerves, 464 
 Precervical sinus, 143, 147 
 Preformation theory, XIII 
 Preformationists, XIII 
 Pregnancy, abdominal, 30, 38 
 
 mammary gland, during, 443 
 
 proof of, 124 
 
 tubal, 30, 38 
 Premolar teeth, 327 
 Premuscle sheath, 305 
 
 tissue, 296 
 Preoptic recess, 531 
 Prepuce, in the female, 424 
 
 in the male, 424 
 Presphenoid bone, 191 
 
 Preterminal area of G. Elliot Smith, 469, 541 
 Primary areas or fields of Flechsig, 558 
 
 germ layers (see also Germ layers), 51 
 
 oocyte, 21, 22, 24 
 
 spermatocytes, 17, 19, 24 
 Primitive body cavity (ccelom), 71 
 
 coordinating mechanism, 504 
 
 entoderm, 133 
 
 groove, 6 1, 86 
 
 gut (see also Archenteron), 51, 72, 316, 370 
 
 intestinal cord, in the chick, 62, 77 
 in Mammals, 66 
 in Reptiles, 63 
 
 organs, 52 
 
 pericardial cavity, 84, 227, 311, 371 
 
 segments, 68, 139, 293, 300 
 
 streak, in the chick, 61 
 
 in Mammals, 65 
 Primordial cranium, 189 
 Proamnion, 80, 104 
 Processus neuroporicus, 454 
 
 reticularis, 511, 516 
 
 vaginalis peritonei, 420 
 
 Production of duplicate (polysomatous) mon- 
 sters, 613 
 
 of monsters in single embryos, 614 
 Progamous determination of sex, 412 
 Projection fields, 558 
 Proliferation islands, 123 
 Pronephric duct, 384, 385 
 Pronephros, the, 384 
 
 pronephric duct of, 384 
 tubules of, 385 
 
 significance of, 385 
 Pronucleus, female, 23, 33 
 
 male, 23, 33 
 Prophase, 4 
 
 Prosencephalon (fore-brain), 454, 457, 467 
 
 diencephalon, 455, 467 
 
 peripheral neurones of, 501 
 
 telencephalon, 455, 467 
 Prosopopagus parasiticus, 600 
 Prostate gland, 402 
 Protentoderm, 54 
 
 of Amphibians, 54, 56 
 
 of Birds, 60 
 
 of Mammals, 66 
 
 of Reptiles, 59 
 Protoplasm, structure of, i 
 Protozoa, cell- division in, 4 
 
 conjugation in, 38 
 Psalterium, see Fornix commissure 
 Pterygoid hamulus, 191 
 
 process, 191, 194 
 Pubis, the, 203 
 Pulmonary artery, 235, 243 
 Pulp of teeth, 325, 326 
 Pulpy nuclei, 179 
 Pulvinar thalami, 533 
 Purkinje cells, 527, 529 
 Pygopagus, 596 
 
 Pyramids (see also Tracts, pyramidal}, 472, 521, 
 523, 524 
 
 Quadrigemina, anterior, see Anterior corpora 
 
 quadrigemina 
 
 posterior, see Posterior corpora quad- 
 rigemina 
 
 Rabbit, formation of amnion of, 104 
 Rabl, concerning origin of vitreous, 575 
 
 concerning sex cells, 404 
 Rachischisis, 313, 605, 607 
 
 cystica, 605 
 Radius, 200 
 Ramus, 196 
 
 communicans, gray, 492 
 
 white, 487, 492 
 Raphe (of epichordal segmental brain), 515 
 
 (of scrotum), 426 
 Rathke's pocket, 319 
 
 pouch, 531 
 Receptors, 448, 451, 457, 460, 462 
 
 visual, 501, 505 
 Recessus postopticus, 454, 531 
 
 praeopticus, 454, 531 
 Recklinghausen, von, concerning deficient 
 
 growth of blastoderm, 607 
 Rectum, the, 341, 400 
 
INDEX 
 
 647 
 
 Red blood cells, 270 
 
 Reduction of chromosomes (see also Matura- 
 tion), 17, 410 
 Reflex arc, 506 
 
 three-neurone, 449 
 
 two-neurone, 448 
 Regnier de Graaf, XIII 
 Reichert, XIV 
 Rejuvenescence theory, 38 
 Remak, views of cell-division, 4 
 Renal corpuscle, 397 
 
 papillae, 396 
 
 pelvis, primitive, 391 
 
 pyramids, 397 
 
 tubules, convoluted, 393 
 
 straight, 391 
 Respiratory system, the, 360 
 
 anomalies of, 368 
 
 larynx, 361 
 
 lungs, 364 
 
 trachea, 363 
 
 Restiform body, 466, 521 
 Rete cords, 404 
 
 ovarii, 407 
 
 testis, 411, 412 
 Retention cysts, 610 
 
 Reticular formation, 465, 471, 515 to 518 
 gray, 516 
 white, 516 
 
 tissue, origin of fibers of, 16 
 Retina, 454, 501, 505, 570 
 
 amacrine cells of, 572 
 
 area centralis, 572 
 
 bipolar cells of, 505, 573 
 
 cone bipolars, 574 
 
 defective pigmentation of, 445 
 
 differentiation of cells of nuclear layer, 572 
 
 distal (first) optic neurone, 573 
 
 fovea centralis, 572 
 
 layer of ganglion cells of, 571 
 of nerve fibers of, 571 
 
 macula lutea, 572 
 
 middle (second) optic neurone, 573 
 
 Muller's or sustentacular cells, 572 
 
 nervous part, 570 
 
 non-nervous part, 570 
 
 ora serrata, 570 
 
 pigmented layer, 570 
 
 primitive nuclear layer of, 571 
 
 rod and cone cells of, 572, 573 
 
 bipolars, 574 
 
 Retterer, concerning lymphatic tissue of ton- 
 sils, 330 
 
 Rhinencephalon, 455, 467, 505, 537, 540 to 
 
 54i 
 Rhombencephalon (rhombic brain), 454, 475, 
 
 495 
 
 Rhombic brain (rhombencephalon), 461, 475 
 cerebellum, 455 
 tela chorioidea, 455 
 
 grooves, 489 
 
 lip, 513, 519, 525 
 
 Rhombo-mesencephalic fold, 454, 475 
 Rhythmical contractions, 98, 112 
 Ribs, the, 184 
 
 capitulum of, 185 
 
 costo-vertebral ligaments of, 184 
 
 foramen trans versarium, 185 
 
 ossification of, 185 
 
 tuberculum of, 185 
 Rods, 501, 505, 572, 573 
 Rolando, fissure of, 554 
 
 substantia gelatinosa of, 520 
 
 tuberculum of, 524 
 
 Roof plate (dorsal median plate), 453, 473, 513 
 Root fibers, afferent, 451 
 
 sheath, the, 440 
 
 Rosenberg's theory concerning vertebrae, 210 
 Rosenmiiller, organ of, 415 
 Rotation of extremities, 151 
 Roux, concerning source of parasitic growths, 
 
 604 
 
 Rubro-spinal tract, 466, 511 
 Rupture of the membranes, 113 
 
 Saccule, 586 
 Sacral flexure, 140 
 Salivary glands, the, 327 
 
 crescents of Gianuzzi, 329 
 
 histogenesis of, 328 
 
 sublingual, 327 
 
 submaxillary, 327 
 Santorini, duct of, 351 
 Sarcoplasm, 309 
 Scala media, 586 
 
 tympani, 586, 587 
 
 vestibuli, 586, 587 
 
 Schaper, concerning development of cerebel- 
 lum, 527 
 
 Scaphocephaly, 212 
 Scapula, 199 
 Schleiden, XIV 
 
 Schmidt, concerning mammary gland, 442 
 Schultz, concerning potentiality of germ cells, 
 
 604 
 Schwann, XIV 
 
648 
 
 INDEX 
 
 Sclera, 575 
 
 Sclerotome, 163, 179, 293, 307 
 Scrotum, the, 420, 426 
 Sebaceous glands, the, 442 
 Secondary egg membranes, 13 
 
 oocyte, 22, 24 
 Secretory function, 329 
 
 Segmental part of epichordal brain, 457, 459 
 Segmentation (see also Cleavage), 40 
 
 cavity, 47 
 
 cells, development of isolated group of, 
 
 to form monsters, 603 
 Segments, primitive, 68, 139, 293, 300 
 
 of segmental brain and cord, 505, 506 
 Semilunar ganglion, 460 
 Seminal filament or spermatozoon, 10, 13 
 
 vesicles, 416 
 
 Seminiferous tubules, 411 
 Sense organs, special, 563 
 
 anomalies of, 591 
 
 ear, 582 
 
 eye, 563 
 
 nose, 579 
 Septa, the, 233 
 
 anomalies of, 285 
 Septal marginal layer, 514 
 Septum aorticum, 235 
 
 atriorum, 233 
 
 medullae, 514 
 
 pellucidum, 469, 552 
 
 spurium, 236 
 
 superius, 233 
 
 trans versum (see also Diaphragm), 372, 
 374, 377 
 
 ventriculorum, 235 
 Serosa, 103 
 Sertoli, cells of, 17, 21 
 Sex cells, 404 
 
 cords, 405 
 
 determination of, 27 
 Sexual elements, 404 
 Sheaths, myelin (medullary), 478, 494 
 
 neurilemma, 478 
 
 Sherrington, concerning effectors and recep- 
 tors, 448 
 
 Shoulder girdle, 199 
 Siamese twins, 597 
 Sigmoid colon, 340 
 
 mesocolon, 381 
 Sinus, cavernous, 251 
 
 confluence of, 252 
 
 coronarius, 254 
 
 frontal, 580 
 
 Sinus, maxillary, 580 
 petrosal, 253 
 sagittal, 253 
 sphenoidal, 580 
 terminalis, 218 
 transverse, 252 
 venosus, 222, 232 
 Sinusoidal circulation, 347 
 Sinusoids, 260, 346, 347 
 Situs viscerum inversus, 354 
 Skeletal musculature, see Musculature, skeletal 
 system, anomalies of, 209 
 appendicular skeleton, 198 
 axial skeleton, 178 
 development of the, 161 
 
 of joints, 205 
 head skeleton, 186 
 notochord, 178 
 ribs, 184 
 sternum, 185 
 vertebrae, 179 
 
 Skeleton, axail (see also Axial skeleton), 178 
 appendicular, (see also Appendicular 
 
 skeleton), 198 
 Skin, the, 437 
 
 anomalies of, 4/14 
 dermis, 438 
 epidermis, 437 
 glands of, 442 
 pigment of, 438 
 Skull, defects of, 604 
 
 development of, 186 
 Smegma embryonum, 442 
 Smith, G. Elliott, concerning archipallium, 469 
 Smooth muscle, 311 
 
 histogenesis of, 312 
 Sole plate, 439 
 
 Somaesthetic area of pallium, 470, 557, 558, 
 Somatic area (see also Pallium, precentral area), 
 
 558 
 
 segmentation, 450, 460 
 structures, 458 
 Somatochrome cells, 489 
 Somatopleure, 71, 105, 370 
 Somites, mesodermic, 68 
 Sperm, 10, 17 
 Spermatids, 17, 19, 28 
 Spermatocytes, 17 
 primary, 17, 24 
 secondary, 18, 22, 24, 28 
 Spermatogenic cells, 17 
 Spermatogenesis, 17 
 Spermatogonia, 17, 24 
 
INDEX 
 
 649 
 
 Spermatozoon, the, 10, 13, 19 
 diagram of, 14 
 discovery of, XIII 
 flagellate, 13 
 Spermium, 10 
 Sphenoid bone, 191, 193 
 Sphenomandibular ligament, 196 
 Sphenopagus, 600 
 Sphenopalatine ganglion, 501 
 Spigelius, lobe of, 349 
 Spina bifida, 605, 606, 607 
 cystica, 605 
 occulta, 606 
 
 Spinal accessory, XI, nerve, 464, 495 
 cord, the, 453, 454, 473, 506 
 Clarke's column, 466, 511 
 dorsal funiculi, 490, 503, 507 
 gray column, 458, 508 
 septum of, 510 
 growth of, 512 
 lack of, 606 
 malformations of, 605 
 ventral funiculi, 507 
 gray column, 458 
 ventro-lateral funiculus, 507 
 ganglion, 490, 491 
 
 cells, unipolarization of, 491 
 meningocele, 606 
 V, 460, 501, 518 
 Spindle, achromatic, 4 
 
 central, 4 
 
 Spino-cerebellar tracts, 466, 471, 512 
 Spiral fibers of spermatozoon, 14 
 filament, 20 
 lamina, 587 
 Spireme, closed, 5 
 open, 5 
 thread, 5 
 
 segmentation of, 18 
 Splanchnic mesoderm, 102, 341 
 or visceral structures, 458 
 Splanchnoccel, 71 
 Splanchnopleure, 71, 105, 370 
 Spleen, the, 283 
 
 cavernous veins of, 284 
 cells, 285 
 
 haematopoietic function of, 284 
 pulp cords of, 284 
 splenic corpuscles of, 284 
 Splenic corpuscles, 284 
 Spongioblasts, 479, 483 
 Spongioplasm, i 
 Spongy bone, 171 
 
 Stapes, 197, 589 
 Sternopagus, 597 
 Sternum, the, 185 
 
 corpus sterni, 186 
 
 cleft, 211 
 
 malformations of, 597 
 
 manubrium sterni, 186 
 
 ossification of, 186 
 
 xyphoid process of, 186 
 St. Hilaire, concerning malformations, 
 Stockard, on production of monsters, 614 
 Stomach, the, 335 
 
 anomalies of, 357 
 
 practical suggestions for study of, 358 
 
 region, 317 
 
 rotation of, 336 
 
 Strahl, concerning the mammary gland, 442 
 Stratum granulosum, 409 
 
 cells of, 410 
 Streeter, concerning the acoustic nerve, 589 
 
 concerning atrium of inner ear, 583 
 
 concerning development of IX, X, XI, 
 cranial nerves, 495, 496 
 
 concerning floor of fourth ventricle, 524 
 
 concerning origin of endolymphatic ap- 
 pendage in man, 583 
 
 concerning origin of genu facialis, 715 
 
 concerning rhombic grooves, 489 
 Stria medullaris, 533, 538 
 
 semicircularis, 543 
 
 terminalis, 543, 548 
 Striae Lancisi, 551 
 Striated involuntary muscle tissue, 311 
 
 voluntary muscle tissue, cells of, 307 
 endomysium of, 311 
 epimysium of, 311 
 fibers of, 308 
 histogenesis of, 307 
 intermuscular tissue of, 311 
 perimysium of, 311 
 sarcoplasm, 309 
 Stylohyoid ligament, 197 
 Styloid process, 192, 197 
 Subclavian artery, 242, 244, 248 
 Sublingual gland, 328 
 Submaxillary ganglion, 501 
 
 gland, 327 
 
 Subperiosteal ossification, 172, 174 
 Substantia gelatinosa of Rolando, 520 
 
 propria corneae, 578 
 Sudoriferous glands, the, 442 
 Sulcus hypothalamicus, 531 
 
 limitans, 477, 512, 524 
 
650 
 
 INDEX 
 
 Sulcus, longitudinalis, 235 
 
 Monroi, 531 
 Superior peduncle of cerebellum, 466, 471, 473, 
 
 530 
 
 Supplemental cleavage, 60 
 Supracondyloid process, 212 
 Supraglenoidal tuberosity, 199 
 Supraoccipital bone, 190 
 Suprarenal glands, 426 
 chromaffin cells, 426 
 cortical substance of, 427 
 lipoid granules of, 426 
 medullary substance of, 427 
 organs, 428 
 
 phaeochrome cells of, 426 
 relation to kidney, 428 
 
 Suprasegmental structures of Adolf Meyer (see 
 also Cerebellum, Mid-brain roof, Cor- 
 pora quadrigemina and Pallium), 450, 
 457, 466, 467, 505, 506 
 characteristics of, 457 
 connections of, see Cerebellum, Mid-brain 
 roof, Corpora quadrigemina, Archi- 
 pallium and Neopallium 
 tracts to (see also Cerebellum, Mid-brain 
 roof, Corpora quadrigemina, Archi- 
 pallium and Neopallium), 466, 471, 
 
 5ii 
 
 Suprasternal bones, 185, 211 
 Sylvii, fossa of, 539, 540, 552 
 Symblepharon, 608 
 Symmetrical duplicity, 594 
 
 anterior union, 598 
 
 complete duplicity, 593, 594 
 
 middle union, 597 
 
 multiplicity, 599 
 
 origin of, 599 
 
 posterior union, 596 
 Sympathetic (autonomic) system, 458 
 
 nervous system, see Nervous system, 
 
 sympathetic 
 Sympathoblasts, 427 
 Symphysis of lower jaws, 318 
 Sympus apus, 611 
 
 dipus, 611 
 
 monopus, 611 
 
 symelus siren, 611 
 Synapta, cleavage in, 41 
 Synarthrosis, 206 
 Syncephalus, 598 
 Synchondrosis, 206 
 Syncytial layer, 121 
 Syncytium of heart muscle, 312 
 
 Syndesmosis, 206 
 Synophthalmia, 608 
 Synosteosis, 211 
 Synotia, 591, 598 
 Synotus, 608, 609 
 Synovial fluid, 207 
 Syringomyelocele, 606 
 
 Tactile corpuscles of Meissner, 438 
 Taenia fimbrias, 548 
 
 of cerebellum, 525 
 
 of cerebral hemispheres, 542 
 
 of medulla, 513 
 
 Tail, gradual shortening of, 140, 144, 145 
 Talus, 204 
 
 Tarsus, bones of the, 204 
 Taste buds (see also Gustatory system), 450, 460 
 Tautomeric column cells, 503 
 Teeth, the, 322 
 
 dental groove, 323 
 papilla, 323 
 shelf, 323 
 
 dentinal canals, 326 
 fibers of, 326 
 pulp of, 325 
 
 dentine, 323, 325, 326 
 
 enamel, 324 
 organ, 323 
 
 membrana preformativa, 325 
 
 milk, 323 
 
 odontoblasts, 325 
 
 permanent, 326 
 
 true molars, 326 
 Tegmental swelling, 517, 535 
 Tegmentum, 524, 538 
 Tela chorioidea, 455, 533 
 Telencephalon (end-brain), 84, 455, 467, 538 to 
 56i 
 
 corpus striatum, 455, 467, 474, 478, 539 
 
 pallium, 455, 467, 474, 538, 539 
 
 rhinencephalon, 455, 467, 505, 537, 540 to 
 
 54i 
 
 Telolecithal eggs (ova), 12 
 Telophase, 6 
 Temporal bone, 191, 193 
 
 lobe, 542 
 Tendons, 167 
 Teratogenesis, 593 
 
 causes underlying origin of monsters, 612 
 malformations involving more than one 
 
 individual, 593 
 
 malformations involving one individual, 
 604 
 
INDEX 
 
 651 
 
 Teratoid tumors, 429, 430 
 
 Teratomata, 604 
 
 Terminal arborizations, 487, 504 
 
 areas of Flechsig, 559 
 Testicle, the, 411 
 
 anomalies of, 432 
 
 cells of, 412 
 
 descent of, 419, 437 
 
 mediastinum testis, 412 
 
 migration of, 418, 422 
 
 processus vaginalis peritonei, 420 
 
 rete testis, 411, 412 
 
 seminiferous tubules, convoluted, 411 
 straight, 411 
 
 stroma of, 412 
 
 tunica albuginea of, 405, 411 
 
 vaginalis propria, 422 
 Testis, mediastinum, 412 
 
 parasitic growths of, 602 
 
 rete, 411, 412 
 Tetrabrachius, 597 
 Tetrads, 18, 22 
 
 origin of, 18 
 Thalamic radiations, 470, 471, 537, 545, 546, 
 
 554 
 
 Thalamus, 467, 478, 505, 536, 546 
 Theca folliculi, 409 
 Theoria generationis, XIII 
 Thigh,_development of, 150 
 Thoracic duct, 275, 279 
 
 region, defects of, 610 
 Thoracogastroschisis, 610 
 Thoracopagus, 597 
 
 parasiticus, 597 
 Thoracoschisis, 382 
 Thymus gland, 285, 333 
 
 anomalies of, 456 
 
 atrophy of, 334 
 
 histogenesis of, 334 
 
 malformations of, 597 
 
 tumors of, 601 
 
 Thyng, concerning anomalies of pancreas, 358 
 Thyreoglossal duct, 332 
 Thyreoid gland, 331 
 
 anomalies of, 356 
 
 colloid secretion of, 331 
 
 epithelial bodies, 332 
 
 its relation to formation of blood cells, 335 
 
 parathyreoids, 332 
 
 thyreoglossal duct of, 332 
 Thyreoids, lateral, 332 
 
 theories concerning, 332 
 Tibia, 204 
 
 Tissues, adenoid, 331 
 
 adipose, 167 
 
 chromamn, 429 
 
 connective, 161 
 
 lymphatic, of the tongue, 330 
 
 mesenchymal, 165 
 
 muscle, 307, 311 
 
 nephrogenic, 392 
 
 osseous, 169 
 
 premuscle, 296 
 
 retroperitoneal, 429 
 
 subcutaneous, 438 
 Toes, development of, 150 
 Tongue, the, 320 
 
 filiform papillae of, 321 
 
 foramen caecum liguae, 321 
 
 fungiform papillae of, 321 
 
 inner vation of, 462 
 
 lingual papillae of, 321 
 
 lingualis muscle of, 321 
 
 tuberculum impar, 320 
 
 vallate papillae of, 322 
 Tonsilla, 526 
 Tonsils, the, 330 
 
 crypts of, 330 
 
 lingual, 330 
 
 lymph follicles of, 330 
 
 pharyngeal, 330 
 
 Tooth tumors, developmental, 327 
 Torneux, concerning malformations of neural 
 
 tube, 607 
 Tornier, concerning production of vertebrate 
 
 monsters, 613 
 Trabeculae carneae, 237 
 Trachea, the, 363 
 Tracts, see also Fascicttli, 
 
 central tegmental, 519 
 
 cortico-spinal, see Tracts, pyramidal 
 
 Flechsig's, 466, 471, 512, 521 
 
 from Deiter's nucleus, 466, 511 
 
 from suprasegmental structures, 471, 512 
 
 Gower's, 466, 471, 512, 521 
 
 gustatory (see also Tractus solitarius) , 462, 
 467, 468 
 
 olfactory, 467, 468, 505, 537 
 
 optic, 467, 468, 505, 577 
 
 predorsal, 467, 530 
 
 pyramidal, 471, 472, 512, 521, 526, 524, 
 558 
 
 reticular formation + ventro- lateral 
 ground bundle system, 504 
 
 reticulo-spinal, 516 
 
 rubro-spinal, 466, 511, 517 
 
652 
 
 INDEX 
 
 Tracts, secondary and tertiary olfactory, 505 
 optic (see also Optic nerve), 505 
 
 spino-cerebellar (dorsal), 466, 471, 512, 521 
 (ventral), 466, 472, 512, 521 
 
 spino-tectal and thalamic, 471, 512 
 
 to Deiter's nucleus, 466 
 
 to suprasegmental structures, 466, 471, 
 
 511, 518 to 525 
 
 Tractus solitarius (communis) of VII, IX and 
 X nerves, 462, 499, 503, 504, 518, 
 521 
 
 Tragus, 594 
 
 Transposition of the viscera, 354 
 Transverse mesocolon, 380 
 Trapezium (bone), 201 
 
 (of medulla), 523 
 Trapezoid, the, 201 
 
 area of His (see also Preterminal area), 
 
 469, 54i 
 
 Tribrachius, 597 
 Tricephalus, 599 
 Trigeminus, V, nerve, 460, 462, 464 
 
 Gasserian ganglion, 460 
 
 spinal V root, 460 
 Trigonum (bone), 213 
 
 (brain), 541 
 Triquetral bone, 200 
 Trochanters, 204 
 Trochlea, 200 
 Trochlear, IV, nerve, 462 
 Trophoderm, 48, 63, 133 
 Truncus arteriosus, 219 
 Tsuda, concerning production of spina bifida, 
 
 614 
 
 Tubal pregnancy, 30, 38 
 Tuber cinereum, 533 
 Tubercles, greater, 200 
 
 lesser, 200 
 Tuberculum of rib, 185 
 
 impar, 320 
 
 of Rolando, 524 
 Tubular form of blastoderm, in chick, 81 
 
 in Mammals, 85 
 
 Tumors of sexual glands, origin of, 603 
 Tunica albuginea, 405 
 
 vasculosa lends, 569 
 
 dartos, 438 
 
 vaginalis propria, 422 
 Turbinated bones, 192 
 Twins, equal monochorionic, 593, 594, 595 
 
 free duplicities, 593 
 
 unequal monochorionic, 594 
 Tympanum, 590 
 
 Ulna, 200 
 
 Umbilical arteries, 103, 222, 241 
 coelom, 338 
 cord, 128, 138 
 anomalies of, 131 
 in Mammals, 107, 138 
 in man, 128 
 length of, human, 130 
 hernia, 113, 622 
 ligament, middle, 115, 401 
 veins, 103, 222, 250 
 Umbilicus, dermal, 101 
 double, 596 
 intestinal, 101 
 Unicornuate uterus, 433 
 Unilateral hermaphroditism, 434 
 Unipolarization of spinal ganglion cells, 491 
 Unna, concerning anomalies of hair, 445 
 Uracho-vesical fistula, 432 
 Urachus, 102, 115, 401 
 anomalies of, 431 
 Urdarmstrang, 66 
 Ureters, the, 391 
 
 anomalies of, 430 
 relations of, to cardinal veins, 260 
 Urethra, the, 401, 424 
 anomalies of, 432 
 Urinary bladder, the, 400, 401 
 "Urinary fistula," 115 
 Urogenital sinus, the, 400 
 system, the, 384 
 anomalies of, 429 
 
 development of suprarenal glands, 426 
 genital glands, 403 
 kidney, 391 
 mesonephros, 386 
 metanephros, 391 
 pronephros, 384 
 urethra, 400 
 urinary bladder, 400 
 urogenital sinus, 400 
 Urorectal fold, the, 400 
 Uterus, the, 415 
 
 anomalies of, 433 
 bicornuate, 433 
 bipartite, 433 
 didelphys, 433 
 fixation of ovum to, 116 
 infantile, 433 
 masculinus, 417 
 relation of placenta to, in 
 unicornuate, 433 
 Utricle, 586 
 
INDEX 
 
 653 
 
 Utriculosaccular duct, 586 
 Utriculus prostaticus, 417 
 Uvula, 526 
 
 Vacuole, 2 
 Vagina, the, 415 
 
 anomalies of, 433 
 Vagus, X, nerve, 462, 464 
 Valves, the, 236 
 
 anomalies of, 285 
 Valvula bicuspidalis, 237 
 
 mitralis, 237 
 
 sinus coronarii, 236 
 
 tricuspidalis, 237 
 
 venae cavae inferioris, 236 
 Valvulae semilunares aortae, 237 
 
 semilunares arteriae pulmonalis, 237 
 
 venosae, 236 
 Vas deferens, 416 
 
 epididymis, 423 
 Vasa aberrantia, 349, 423 
 
 efferentia, 416 
 Vascular arteries, 240 
 
 blood vessels, 216 
 
 blood and blood cells, 267 
 
 changes in the circulation at birth, 265 
 
 development of the, 216 
 
 heart, 227 
 
 histogenesis of blood cells, 267 
 
 lymphatic system, 273 
 
 system, anomalies of, 285, 595 
 
 veins, 250 
 
 Vasculogenesis, principles of, 224 
 Vegetative pole (macromere), 52 
 Veins, accessory hemiarzygos, 260 
 
 anomalies of, 288, 607 
 
 ascending lumbar, 260 
 
 axillary, 263 
 
 azygos, 259 
 
 basilic, 263 
 
 brachial, 263 
 
 cardinal, 251, 253, 255 
 
 cavernous, 282 
 
 cephalic, 262 
 
 cerebral, 251 
 
 common iliac, 259 
 
 femoral, 265 
 
 fibular, 264 
 
 hemiazygos, 260 
 
 hepatic, 262 
 
 inferior sagittal, 253 
 
 internal spermatic, 258 
 
 jugular, 254 
 
 
 Veins, jugulocephalic, 264 
 
 lateralis capitis, 251 
 
 of Galen, 253 
 
 omphalomesenteric, 102, 218, 250 
 
 ovarian, 258 
 
 portal, 261 
 
 primary ulnar, 262 
 
 radial, 263 
 
 renal, 257 
 
 revehent, 256 
 
 saphenous, 265 
 
 sciatic, 265 
 
 subcardinal, 256 
 
 subclavian, 254, 266 
 
 subintestinal, 71 
 
 supracardinal, 259 
 
 suprarenal, 259 
 
 testicular, 258 
 
 tibial, 264, 265 
 
 umbilical, 103, 222, 250 
 
 vitelline, 102, 218 
 Velum, anterior medullary, 526 
 
 posterior medullary, 513, 526 
 
 transversum, 454, 534 
 Vena cava, inferior, 255, 257 
 
 superior, 254 
 Veno-lymphatics, 280 
 Ventral cephalic fold of brain, 453 
 
 mesentery, 377 
 
 mesogastrium, 377 
 
 root fibers, see Efferent root fibers 
 Ventricle, 361 
 
 of Verga, 552 
 Ventricles of the brain, 456 
 
 fourth, 456, 478- 
 
 lateral, 456, 542 
 
 anterior horn of, 542 ^* 
 descending horn of, 542""" 
 posterior horn of, 542 
 
 third, 456, 478 
 Ventricular septum, 233 
 Ventro-lateral plate, see Basal plate 
 Vermiform appendix, 341 
 Vermis, 526 
 
 Vernix caseosa, 437, 442 
 Vertebrae, the, 179 
 
 alternation of vertebrae and myotomes, 
 
 anomalies of, 209 
 
 blastemal stage of, 180 
 
 bodies of, 180 
 
 cartilaginous stage of, 180 
 
 costal process, 180 
 
 intervertebral fibrocartilage, 180 
 
654 
 
 INDEX 
 
 Vertebrae, ligaments of, 184 
 
 ossification stage, 182 
 
 sclerotomes of, 178 
 Vertebrae cervical, defects of, 604 
 Vertebral arch, 180 
 
 articular process of, 182 
 
 spinous process of, 182 
 
 transverse process of, 182 
 Vertebrate, the definition of, 450 
 
 differentiation of the anterior end of, 450 
 
 nervous system, see Nervous system, ver- 
 tebrate 
 
 Vesical fissure, 432 
 Vesicle, auditory, 582 
 
 blastodermic, 134 
 
 optic, 140, 564 
 Vesicles, brain, 454, 473 
 
 seminal, 416 
 Vestibular ganglion cells, 589 
 
 membrane (of Reissner), 587 
 
 nerve, 589 
 
 part of acoustic (auditory) nerve, 462 
 descending root of, 462 
 
 pouch, 583 
 Vestibule, 460 
 Vestibulum vaginae, 424 
 Vicq d'Azyr's bundle, 537 
 Vignal, concerning the myelin sheath, 494 
 Villi, chorionic, no, 118 
 
 fastening, 123 
 
 floating, 123 
 Visceral mesoderm, 71, 83 
 
 musculature, see Musculature, visceral 
 
 neurones, sympathetic, 451 
 
 or splanchnic structures, 458 
 Visual area of pallium, 470, 557, 558 
 
 cortex, 557 
 Vitelline arteries, 101, 241 
 
 circulation, 220 
 
 duct, 113 
 
 membrane, n 
 
 plexus, 217 
 
 veins, 102, 218 
 Vitellus, n 
 Vitreous, 575 
 
 humor, 575 
 Voral cords, superior, or false, 361 
 
 true, 361 
 
 Volar arch, superficial, 248 
 Voluntary muscle, striated, histogenesis of, 307 
 
 origin of, 293, 294 
 Vomer, 192, 194 
 Von Baer, XIII 
 
 Von Baer, concerning cell differentiation, 51 
 
 Von Baer's law, 384 
 
 Von Loewenhoek, concerning the discovery of 
 
 the spermatozoon, XIII 
 Von Spec's embryo, 86, 136 
 
 Waldeyer, concerning site of fertilization, 38 
 
 " Waters," the, 113 
 
 Webs between digits, 151 
 
 Weismann, concerning fertilization, 38 
 
 Wharton's jelly, 129 
 
 Wheeler, diagram showing amitosis, 4 
 
 White columns (see also Dorsal funiculus), 503 
 
 matter of cerebral hemispheres, 554 
 of cord and segmental brain, 504 
 
 ramus communicans, 487, 492 
 Wiedersheim, concerning the mammary gland, 
 
 443 
 concerning duplicity with double gastru- 
 
 lation, 600 
 concerning the fertilization of eggs of 
 
 sea-urchin, 34 
 Wilson, J. F., concerning intermediate region 
 
 in the cord, 524 
 
 concerning intermediate plate, 524 
 Winslow, foramen of, 378 
 Wirsung, duct of, 351 
 
 Wlassak, concerning the myelin sheath, 494 
 Wolffian duct, 386 
 
 ridge, 388 
 "Wolf's snout," 212 
 
 theory of epigenesis, XIII 
 Woods, concerning sex cells, 404 
 Wyder, concerning site of fertilization, 38 
 
 X-chromosome, 28 
 Xiphoid process, 186 
 
 malformations of, 597 
 Xiphopagus, 597 
 
 Y-chromosome, 29 
 
 Yolk, comparison of amount of in forms of 
 
 gastrulation, 57, 64 
 entoderm, in Amphibians, 54 
 in Birds, 60 
 in Mammals, 66, 68, 81 
 granules, 12 
 
 lack of, in Mammals, 104 
 plug, 54 
 sac, 99, 135 
 
 formation of in chick, 99 
 function of, 100 
 in Mammals, 104, 106 
 in man, 87, 113 
 
INDEX 
 
 655 
 
 Yolk sac, roof of, in chick, 80, 8 1 
 in Mammals, 85 
 in man, 87 
 stalk, loo, 107, 137, 317 
 
 Zander, concerning the nails, 439 
 Ziegler, concerning malformations of neural 
 tube, 607 
 
 Ziegler's fusion theory of symmetrical duplic- 
 ity, 599 
 Zona pellucida, n, 34, 409 
 
 radiata, 409 
 Zonula Zinnii, 578 
 Zonular placenta, no 
 Zygomatic bone, 194 
 Zymogen granules, 354 
 
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