Talk:Book - Human Embryology (1945)

From Embryology



W J HAMILTON, md,dsc,frsp

Professor of Anatomy in the University of London at Channg Cross Hospital Medical School sometime Regius Professor of Anatomy in the University of Glasgow formerly Professor of \natomy in the University of London at the Medical College of St Bartholomew s Hospital

J D B O Y D , M A M Sc M D

Professot of Anatomy m the University of Cambridge and Fellow of Clare College Cambridge sometime Professor of Anatomy in the University of London at the London Hospital Medical College



Professor of Anatomy m the University of Wisconsin

'And surely ue are all out of the eomputation of our age and eter^ man is some months elder than he bethinks him for tie hie moie haie a being, and are subject to the actions of the elements and the malice of diseases, in that other World the truest Microcosm the IVomb of our Mother* Sir Thomas Brovvnes Rehgio Medici 1642



First Published ------ ig^5

Reprinted ------- ig^6

Reprinted 1947

Second Edition ig52

Reprinted ------- ig^G

Reprinted ------- iggy

Reprinted 1959


W J. Hamilton,

J D Boyd,

H W Mossman


Printed in Great Britain at the Works of


To the memo^




whom thejirst edition oj this work iv.



I HIS book IS a presentation of the subject of human embrjology in the light of the aclvanc which ha\e been made in it during the past twenty years An attempt has been made to ht the developmental history of the embryo into the background of the physiological changes in the maternal organism and to correlate the development of embryonic function with that of its form \Nc have aho tried to introduce the concepts of development which have been estab lislied b\ the work of experimental embryologists (Chapters I and VIII) These concepts are of c,reat theoretical, and we believe practical importance but, unfortunately, they do not readily lend themselv es to elementary exposition further as they are based almost exclusively on the results of experiments on animals below the mammals it is extremely difficult to present them without assuming a knowledge of comparative Embryology A brief survey of compara tive vertebrate development is therefore, given in the last chapter and if the reader finds difficulty with Chapter VIII it is recommended that he studies Chapter XVI before proceeding with the attempt at mastering the concepts of determination and the organizer Special attention is paid m Chapters V and XVI to placeniation and the embryonic membranes as a knowledge of these aspects of embrvology is of special importance m the study of the problems of embryonic and foetal nutrition and of the prenatal relationship between the mother and the child

References to embrvological literature arc full not however with the intention that the student shall consult all or even more than a very few of them We feel lint direct reference to the original literature is a habit that the student should acquire early and tint an extensive bibliography gives an opportunity to track down original observations on any aspect of a bio logical problem which may particularly interest the reader For this reason titles of papers have been deliberately given in full even at the expense of lengthening the text It is felt that the bibliographies may also be of service to more senior students

A sound knowledge of embryology cannot be obtained solely from a textbook We recommend students, therefore to obtain access to serial sections through mammalian or if possible human embryos and to study them carefully Many difficulties in organogenesis can quickly be resolved by reference to such scries and the drawing of a number of representauve sectiors provides n most excellent discipline for acquiring a knowledge of the basic structure of the mammalian body

London W J H

October 1944 J D B


Tor this edition the whole text has been extensively revised md many of the chapters have been completely recast and rewritten It has been considered advisable to give a brief intro ductory statement to eacii chapter so as to orientate the reader \n attempt Ins been made to keep the text as short as possible and up to a point we feel that we have succeeded Excluding the index the subject matter has been increased from 343 to 41 1 pages This increase is mamly due to the increase in the number of illustrations from 364 to 433 A large number of photo micrographs have been added and many of the illustrations of the previous edition have been either redrawn or replaced C onversion from squared off blocks to either cutout or deep etchrd blocks has been widely carried out \\c have also taken the opportunity to introduce a difTeicnt type face and to shorten the length of the line These typographical altcntions are also partly responsible foi the increase in the size of the book °

\V J H J D B H W M


We wish to acknowledge our indebtedness to the Carnegie Institution of Washington for the valuable help we have received fiom the numerous publications on embryology by members of the Staff and others associated with them. We would thank especially Dr G W Corner, Director of the Embiyological Laboratory, for original photographs of human embryos at different stages of development. To Dr A. T, Hcrtig and Dr J. Rock we are indebted for photographs of early human embryos. We are especially indebted to them for photographs of the two cell stage and the unattached human blastocyst.

We wish to thank the following foi permission to reproduce illustrations • — (a) The Wistar Institute of Anatomy and Biology for illustrations from the American Journal of Anatomy, (b) The American Journal of Obstetncs and Gynecology for Fig. 23 (c) Surgery, Gynecology and Obstetrics for

Fig 18A. [d) Journal of Anatomy. All illustrations from the above sources have been acknow ledged m the accompanying legends


We thank the Blakiston Company foi permission to reproduce Fig 424 from Snell’s Biology of the Laboratory Mouse, also Messrs Arnold, London, and Professor S J Cameron, of Glasgow, for permission to reproduce Fig. 91,

In the present edition we have to thank Professor A. Pomfret Kilner for permission to leproduce Fig, 176. We also wish to thank Mr P. J Blaxland, F.R.C S , for permission to reproduce Fig. 260 and the late Dr A. Peacock for Fig 370.

All the new illustrations are from the skilled draughtsmanship of Mr Frank Price and we have to thank him for his skill and patience We are indebted to many readers, and especiallv to Dr W Hammond of Syracuse University, for their constructive criticism and for pointing out a number of ambiguous statements.

We record our indebtedness to Di R. J Haiiison and to Dr T. M Roberts for their help in leading the manuscript and proofs and for their constructive criticism We wish to express our thanks to Mr E, J Park, technician in the Anatomy Department, Charing Cross Hospital Medical School, for the care he has taken in “pasting up” the annotations of the new illustrations He has also given us much help in the checking of the references

We have been fortunate in the cordial lelationship which has existed between us and Messrs W. Heffer & Sons Ltd , the Printers and Publishers Mr R G Heffer has ahvays been willing to meet and satisfy our many demands for more illustrations Finally, we wish to thank Mr G Newman, works director of Messrs W Heffer & Sons Ltd , for his patience, resourcefulness and enthusiasm





, Introductor\ Concepts

Chapter I

Chapter II

Formation Maturation and Stiucture of the Germ Cells 9

Chapter HI

CvcLic Chanc»es in the Female Genital Tract - - 22

Chapter IV

Fertilization Cleavage and Formation of the Germ Lavers - 37

Chamer V

^The Implantation of the Blastocyst and the Development of the Foetal Mem

BRANES Placenta and Decidua 60

Chapter VI

The Fate of the Germ Lavers and the Formation op the Essential (Primary)

Tissues including the Blood 95

Chapter VII

Grow ni of the Embrv o Dtv elopment of External Form Estimation of Em bryonic and Foetal Age

Chapter VIII

, Determination Differentiation the Organizer Mechanism Abnormal Develop ment and Twinning

Cardio Vascular Sv stem

Chapter I\

Chapti-r X

Alimentarv and Respiratorv Systems Pleural and Peritoneal Cavities Chapter XI



Urogenital System





Chapter XII

Nervous System 263

Chapter XIII

Skeletal System 334

Chapter XIV

Muscle and Fascia 335

Chapter XV

Integumentary System - - - .___-37o

Chapter XVI

Comparative Vertebrate Development - - - 377

Appendix - 4°9





Members of all multicellular animal species (Metazoa) have a more or less limited life span Consequently if a species is to sur\it.e a mechamsm must exist for the successive production of new generations of that species This process is called reproduction In most metazoan species, including the vertebrates reproduction is efTected b> a complicated process involving the presence of two sexes male and female and the production b> each of these sexes of specialized sex cells called gametes The organs which produce the gametes are known as the gonads or primary sex organs, those of the male are the testes those of the female, the o ones The male gametes are named spermatozoa the female gametes o a The union of a spermatozoon with an ovum is called fertilization and results m the formation of a single cell, a z^gole^ The relationship between the members of one generation of an animal species and those of another is said to be an hereditary or a genetic one It is obvious that a zygote has an hereditary relationship by way of the gametes from the fusion of which it resulted with a male and a female parental organism

In addiuon to the primary sex organs each sex is usually characterized by the presence oi accessory sex organs which transmit the gametes from the gonads In the male the accessory sex organs may include an intromiitent organ the^mr which enables the sperms to be deposited in the female genital tract In the female the accessory sex organs frequently include a special receptacle for the sperms the vagina and a brood chamber, the uterus for the reception and incubation of the zygote The male and female sexes are usually further distinguished by the presence of yet other differences both physical and mental, such as mammary develop ment hair distribution and patterns of behaviour not directly concerned with reproduction These arc known as secondary sexual characters


The zygote which has been formed by the fusion of a male and female gamete is a single celled organism After a longer or shorter period this unicellular organism wall become pro grcssivcly transformed by the processes of cell division cell migration growth and differentiation into a multicellular mature member of its species The term development is used to describe these progressive changes After a period of matunly, of variable duration depending on the species retrogressive changes leading to senility and eventually death occur

Consequently in the earlier stages of development structural changes occur and organs appear before the necessity or possibility for their functional activity Thus they have a future or prospectus rather than an actual or immediate value in the life of the developing orgamsm This can be expressed by saying that structure in the embryo is frequently antecedent to function Although It IS obvious that no defimte limit in this total developmental process can be fixed as the end of a stnetiv embryonic period still in general, the processes discussed m this book include almost all of those antecedent to function and most others up to the establishment of the basic functional patterns characteristic of the human foetus dunng the last six months of prenatal life In other words embryology is usually concerned with an organism from the zygote stage up to the anatomical cstabhshment of the definitive organ systems and often into their early functional period An exception to the latter would of course be the reproductive system which matures functionally relatively late

The term ontogeny is used to describe the complete life period of an individual organism Embryolo^ is the study of the earlier stages of development md in the true mammals including



man, is restricted to the developmental processes occurring before birth, i e., in the prenatal period of life It must be stressed, however, that there are no essential differences between prenatal and postnatal development, the former is more rapid and results m more striking changes in the shape and proportions of the organism, but the basic mechanisms are very similar if not identical m both periods Indeed in many lower orgamsms (see Child, 1941, for details) the ability to revert under certain conditions to the embryonic type of development is retained throughout hfe and the phenomena of repair and regeneration, which are present to some degree m the adults of even the highest animal types, present fundamental similarities to embryonic processes. Ageing in most metazoa, however, has a marked retarding effect on developmental reparative changes (du Nouy, 1936).

Developmental changes can be contrasted with the day by day non-progressive and, in generalj much more rapid physiological changes, such as respiratory, circulatory, digestive and nervous activities, which are directly essential for the maintenance of life. When the earlier embryonic stages are considered this contrast is particularly striking, for developmental changes are then at a maximum and the organ systems of the body are not yet established to perform the physiological activities peculiar to them in later life. Such earlier stages may be referred to as the pre-functional period of development, the later stages constituting the functional period It must be emphasized, however, that at all stages of development the embryo is a living organism capable of maintaining itself as such. As it grows and differentiates, new mechanisms are continually coming into activity so that the organism may cope with changing internal and external conditions, for embryos not only grow and differentiate but also live, and the requisite physiological functions must be exercised during these developmental alterations. If embryos are to maintain themselves, their structure must be such that for each developmental period an adequate physiological performance is assured. Equipped with this structural organization an embryo might live indefinitely at any particular stage if no changes in itself or m its environment rendered that level of organization inadequate But changes in the embryo do occur as a function of time and as the requirements for existence are progressively modified. The new needs are met by the development of new devices which one after another are discarded or remodelled when the needs change and pass. “Thus one meets with a series of increasingly complex ephemeral organs and structural arrangements characterizing the periods of development that space off the anabasis of the embryo from the microscopic one-celled egg up to the large, highly specialized fetus of later stages” (Streeter, 1942).


In its evolution as a science embryology has passed through several stages.* It was at first, and for the greater length of its history, purely descriptive, but as detailed knowledge of the development of related types became established a science of comparative embryology arose. This, in turn, was succeeded by the attempt to introduce an analytical embryology based on experimental methods This experimental embryology, which was first properly established by Roux (1888) as Entwicklungsmechanik (developmental mechanics), has widened the scope of the science, so that now the investigation of the causal mechanisms of development has been added to the descriptive and comparative approaches Observational embryology can merely record the sequence of developmental events, only experiment can acquaint us with the forces involved and their possible modes of action During the past fifty years the experimental approach, using lower forms, has resulted in the elucidation of many fundamental problems of development but, unfortunately, the possibilities of using similar experimental procedures on embryos of the higher, and particularly viviparous, types are still very restricted and, of course, in man are non-existent

  • For the history of embryology consult Russell (igiGj 1930)5 Nordenskiold (1929); Cole (1930)5 Needham

(1934); Meyer (1936, 1939), and Adelmann (1942)



Human embryology is, strictly speaking still in the descriptive stage However, the application of the concepts of comparative and experimental embryology has added greatly to the rational interpretation of the processes of human development


The value of the study of embryology to the medical student is fivefold —

(i) From the general biological aspect it gives an understanding of how the different organs and tissues develop from a single cell (the fertilized ovum) into a complex multicellular organism As the study of the development of structure is linked vMth that of function embryology provides a basis for the understanding of the functional activity of the organism during development Further an appreciation of the causal factors underlying development, about which v\e have only the tentative beginnings of knowledge is only possible after normal development has been considered It must be realized that the study of development m a single complex species (e g as in this case, man) will not always be easily understood Indeed in order to obtain a clear understanding and appreciation of developmental processes in man. It is often necessary to refer to sub human ty^ies since in man some sequences of dev elopment have become shortened to such an extent that the basic primitive steps in the process are difficult to discern, or because sufficient stages of human material are not available for study This is particularly the case in the early stages of development Experiments which can be earned out in lower types can not of course be perform^ on the human subject so that the argument from analogy must often be used

(a) From the vocational aspect the study of dev elopment in a great many instances gives a rational explanation of the relationships and position of many normal adult structures e g the nervesupply of the diaphragm by cervical nerves the asymmetry of the veins in the abdominal and thoracic cavities the nerve supply to the tongue

{3) Embryology includes not onh the development of the embryo but also the development of the membranes which connect the foetus to the mother le placcntation m viviparous vertebrates A knowledge of the development relations and properties of these membranes w essential in order to understand obstetrics and as a basis for advances in this subject Such a knowledge is also obviously necessary for the understanding of the physiological relationship between the foetus and the mother

(4) Many pathological conditions can only be understood m the light of normal and abnormal development Until recently the relationship of embryology to medicine was mainly ofa theoretical nature Modern experimental work on lower types has thrown light on such problems as growth and regeneration of tissue formation of certain tumours, transplantation (* e grafting of tissue) and explantation (1 e the growth on a suitable cultural medium, of isolated parts or individual organs) There seems little doubt that these aspects of ^bryology are destined to make profound contributions to our conception of growth and r^arative processes and also possibly to our understanding of many pathological phenomena

(5) As the student continues his studies through the basic medical sciences and into the c inical subjects embryology will be appreciated more and more as a great correlator of other morphological disciplines such as anatomy pathology, physical diagnosis and surgery and even of many physiological aspects of mediane


Developmental changes occurring m one group of animals do not necessarily occur in all IS described later (Chapter X\ I) the ova (eggs) of different groups do not

^ 'Contain an equivalent amount of stored nutritive material (yolk or deutoplasm) and this is ^related with adaptive changes in the method of development ^\hen the amount of yolk



IS large, as in birds, the embryonic period of development is long enough to allow adult-like characters to appear before hatching. When the amount of yolk is less, as in Amphibia, the young are hatched as larvae (i.e , tadpoles) which lead an active life and derive nutriment from their external environment before assuming, by a process of metamorphosis, the adult form. Again, eggs of many species are shed into water and undergo their development in an aqueous medium, whereas m other types the eggs are laid on dry land, possibly in desert regions, with no access to water other than that with which they are originally endowed by the maternal organism. The latter variety of eggs show adaptations which tend to preserve the scanty water reserves These include the development of special enclosing shells or membranes and changes in embryonic metabolism such as the excretion of the end products of nitrogenous metabolism as the relatively insoluble uric acid (uricotelic metabolism) and a high resistance to ketosis (Needham, 1942). Yet again, as m the group of true mammals, the egg, with practically no reserves of yolk or of water, is fertilized by the sperm inside the maternal body, and a part of the maternal genital tract, the uterus, becomes modified for the retention and nutrition of the developing individual. This arrangement whereby the egg develops within the uterus long after its meagre yolk supply is exhausted is known as viviparity In such circutnstances a specialized apparatus, the placenta, is elaborated by both embryonic and maternal tissues to serve as a mechanism for the transfer of food and oxygen from the mother to the embryo and of the waste products of metabolism from the embryo to the mother As man is a true mammal this placental mechanism is present during human development and is described m Chapter V. Many other examples of developmental adaptation to special environmental conditions are known and some are referred to m Chapter XVI.


What an organism becomes in the course of development is the resultant of two factors, its heredity and its environment Heredity acts by way of internal factors present in the fertilized egg Itself The modem science of genetics has demonstrated that many, if not all, of the internal factors are present in the nuclei of the gametes They are the so-called genes which are probably complicated protein molecules situated m the chromosomes As the genes of a zygote are derived from both maternal and paternal gametes the characters of the developing organism are derived from both mother and father * It is now well established that the special characteristics of an organism (e.g , hair type, eye and skin colour, etc ) are due to its nuclear genic equipment. The more general characteristics (e g , those enabling us to classify it as a man or a chimpanzee, as a primate or a carnivore, as a mammal or a reptile) are controlled by factors which are not yet understood It is suspected, however, that in addition to the nuclear genes the general cytoplasm of the egg may have some influence in the establishment of the specific, generic and class characteristics of an organism (Needham, 1942, and Harvey, 1942).

Environment acts on the development of the egg as a whole by way of external factors not present in the egg itself Such factors are gravity, temperature, light, chemical agents and nutritive substances There is, however, an interaction within the developing organism of the various genes, chemical substances, and products from the different tissues and organs upon one another. This is often spoken of as the internal environment All of this internal environment is, however, in the last analysis a part of heredity, in contrast to external environment which IS what is ordinarily meant when the problems of heredity and environment are discussed

Heredity and environment are often brought into a false antithesis, since it is assumed that they act in opposition to each other. The characters of an adult organism, however, are produced by the interaction between the genetic factors and the environmental ones An

  • Owing to the nature of the hereditary mechanism, however, blending of particular characters of mother

and father does not usually oecur On this point, and on genetics generally, the student should consult a textbook of genetics, e g , Gruneberg (1947), Ford (1942), Castle (1940), Waddington (1939)1 Goldschmidt (193°)


alteration in either of these components ma> lead to variation or if excessive to abnormal dev elopment or ev en death Genetic \ anaUon results from changes m the genetic constitution due to mutation or more frequentl), to changes in chromosomal or genic pattern (recom bination) Environmental variation results from changes in the environment in v\hich the genes operate The actual organism produced by the normal interaction between heredity and environment is called a phenotype an oi^anism judged by its genetic constitution alone is a senot^pe Phenotypically similar organisms may be genotypically different Thus the genetically hybrid children of a pure dark brown eyed parent and a pure blue eyed one although possessing both blue eye and dark brown eye genes all actually have eyes as dark as their dark eyed parent In other words their phenotype is ‘dark eyed, but their genotype IS a hybrid between dark eyed and blue eyed In genetical terms one parent is homo.^)gous for dark brown eyes the other homozygous for blue eyes and the children are hetero^gous possessing genes for both dark and blue eyes On the other hand alterations in the environment may result m the simulation of characters associated w ith one genoty pe in an organism possessing quite a different genotype Thus genotypically dissimilar organisms can be made to be phenotypically similar (the phenocopies of Goldschmidt 193^)

Owing to inira uterine gestation the environment of the developing mammalian embryo IS tolerably constant and more or less optimal Environmental variation in this vertebrate class therefore is difficult to study m the prenatal penod It is well established, however that environmental differences of quite subtle kinds (eg number of embryos in uterus age of mother number of previous pregnancies and certain virus diseases such as rubella m the mother) do influence the course of development Maternal hormones too, may have some efTect (Chapter V)

The experiments of Walton and Hammond (>938) have demonstrated very clearly the effect of environment on mammalian development These workers by artificial msemina tion produced reciprocal crosses of the Shetland pony and the Shire horse At birth the cross bred foal from the large (Shire) mother and the small (Shetland) stallion is three times as large as that from the small (Shetland) mother and the large (Shire) stallion As the cells of both foals have similar chromosomal contents and presumably similar genes the size differences must be due to the environment provided by the mother How the size is controlled to suit the size of the maternal organism has not been determined It may be limited by the amount of nutrition provided by the maternal circulation by the maximum size of the uterus or by some unknown (maternal placental or foetal) hormonal influence

The occurrence in man of like {identical) and unlike {fraternal) twins provides excellent material for assessing the importance of changes in cnv^^onment on the subsequent history of individuals of identical or different genetic structure The results of such assessment are considered in Chapter VIII

The question whether environmental influences affect only the individual organism con cerned or whether such influences have a transindmdual action (1 e the effects are earned over to the next generation) has been much debated Modem biologists are almost unanimous in their opposition to the so called transmission of acquired characters in the Lamarckian or neo Lamarckian senses of the term (Huxley 19412) All animal characters are acquired in the course of development by the interaction of the genetic equipment with the environment and as has been stated earlier vanations in cither of these scu of factors may result in alterations in the course of development There is however no acceptable evidence that a character of the body of an organism arising in response to an environmental stimulus is able so to impress Itself upon the genes that in subsequent gcneraUom the character will appear in the absence of the stimulus The internal factors (genes) can be permanently changed as the result of

direct action upon them of irradiation which is of course an environmental stimulus However environmental stimuli such as those of bght, temperature and food which act directly on the body tissues, but hav e no direct action on the genes within the germ cells cannot produce hereditary modifications




The major problem m embryology is the appearance, during development, of complexity of form and function where previously no such complexity existed. Historically two contrasting points of view have been held on this problem. One of these, the so-called theory of epigenesis, considered that during development there is actually the creation of new structures; whereas the other, the theory of preformation, maintained that a pre-existing diversity is already present in the fertilized egg (or in the sperm) and that future development consists merely in the unfolding and rendeiing visible of this innate diversity The embryological investigations of the past hundred years have demonstrated most conelusively that the actual processes of development are of an epigenetic nature but the doctrine of preformation has been reintroduced, in a much modified form, in the explanation of the facts established by modern genetics. “The modern view IS rigorously preformatiomst as regards the hereditary constitution of an organism, but rigorously epigenetic as regards its embryological development” (Huxley and de Beer, 1934).


Needham (1933 and 1942) has classified the fundamental morphogenetic mechanisms under the headings of giowth, diffeientiation and metabolism. Growth is increase m spatial dimensions and in weight, it may be multiplicative (increase in number of nuclei and (or) cells), auxetic or intussusceptive (increase in the size of cells) or accretionary (increase in the amount of non-living structural matter). Differentiation is increase in complexity and organization This increase may be in the number of varieties of cells and may not at first be apparent (“invisible” differentiation, e g , determination of fates, segregation of potencies, loss of competence, etc , see Chapter VIII), but, when apparent (“visible” or “manifest” differentiation), constitutes histogenesis. Differentiation may be manifested as an increase in morphological heterogeneity resulting in the assumption of form and pattern and in the appearance of recognizable organs or organ pnmordia {organogenesis). Metabolism includes the chemical changes in the developing organism

In the normal development of an embryo these fundamental ontogenetic processes are all closely interlinked, constituting an integrated system, “They fit in with each other in such a way that the final product comes into being by means of a precise co-operation of reactions and events” (Needham, 1942).


From a descriptive point of view the principal stages in metazoan embryological development are —

(1) Maturation. This is the process associated with the formation of mature female and male germ cells (gametes — ova and sperms) from the undifferentiated germinal epithelium (oogonia and spermatogonia) of the female or male gonads. During maturation of both oocyte and sperm a reduction of the chromosomes to one-half of the somatic number occurs. This reduction results from a specialized mode of nuclear division called meiosis. In this stage the female sex cell grows to a relatively large size due to storage of yolk. The male sex cell remains small but undergoes changes in shape and internal structure which make it a motile orgamsm Consequently the mature gametes are highly specialized cells which when fully differentiated do not usually live long unless they take part in fertilization

(2) Fertilization. This is the fusion of a female and a male gamete. It results in the formation of the zygote or fertilized ovum. This process has two fundamental objectives;

  • Increase in number of nuclei and number of cells is not necessarily growth in the sense of size expansion.

Cell dmsion, for example, occurs without size expansion in the earlier stages of cleavage (Chapter IV) Nevertheless nuclear and cell division are so inumately bound up with growth that Needham classifies them with true growth processes


fim tlic initntion of cm])rVQmcJc>_clapmcDt^ second the reitor\tioaofth^iromo

somc number of the species and hence the ichicvcment of biparentnl mhentance with all its important implications The z\^.otc ahhoiii.h rcsullini; from the fusion of two biqlil) specialized cells is regarded as being the most tmspeciahzed (umlifTefentiaitd) of all metazoan cells

(3) Cleavage The zvgotc soon undergoes repeated subdisision In mitosis so that a number of cells Uasiomrt} each mnch smaller than tlic o%um itself is produced Tims the unicellular z>gotc becomes a multicellular organism

(\) Blastula The blastomctes at the end of clcwagc arc cscntualK grouped to form a hollow sphere of cells the hlisiiila or in mammals the hlastocjst Uxpcnmenis on and intrasiiam staining of the hlastulae of lower \crtchrites especially Amphibia hate made U possible to delimit the future fate of all regions of the blastiila and thus to ascertain their potency ic what localized areas become 111 normal development The dincrcnt areas of the blastula can be referred to as presumpine organ regions thus one region is presumptive notochord another presumptive neural plate etc

{5) Gastrula The blastula stage is succeeded In the gastnila stage which results from changes m position and displacements (morphogenetic movements) of the v anouv presumptive regions of the blastula Castnilation results in the establishment of the three pnmarv ^erm laverSi trvladtm and rcWrrwi and brings the presumptive orgam of the emhrso into

the positions m which they will undergo their sulwetjuent development In reptiles birds and mammals this gastrulaiion period is represented bv the embryonic disc and primitive streak stages

(fa) Neurula The gastruh sta^e iv followed In one m which the neural plate and the axial embryonic structures are elaborated In Amphibia this » known as the ncurula This stage corresponds roughly to the somite stages in human tlevrlopment (Chapter IV) At the end of the ncurula or somite stage of development the general pattern of the embryo is well established and later embryos ire said to be in the so-called functional period of development

FUNCTIONAL PERIOD OF DEVELOPMENT The earlier embryonic stages which have lieen descnlied above result in the appearance of the general embryonic pattern before the onset of specific function m the pnmordia of the different organs and (issues which arc dilTcrentiaicd in these stages Functions in the general sense are carried out at all times as all the cells are undergoing mctaljohc changes and must work to live Hut with the onset of specific functions such as beating of the heart contraction of muscles, secretion by glands etc the embryo enters on what may be called the functional period of development Different organs of course commence to function at different times and no sharp distinction can be made between pre functional and functional stages growth and differentiation proceed in both Ncvertlielevs it is useful to consider the processes of earlier stages as blocking out the mam cmbrvonic organ systems which will subsequently be elaborated under the influence of the specific functions which they perform The functional influence does not by any means replace the genetically determined general pattern of development, but It will be seen m later chapters that m the dev clopment of many organs and tissues (e g , the heart and blood vessels and the skeletal system) the effect of the function of an organ on its development is considerable

TJic functional stage of development results in the different organs and tissues coming into physiological relationship with each other and thtreforc m a degree of integration of total function which cannot exist m earlier stages The integration is facilitated and indeed rendered possible bv the differentiation of the vascular and nervous systems and the onset of function in the endocrine glands The endocrine glands arc of special importance in the later stages of cmbryological and m post natal development The growth hormone of the pituitan the



thyroid hormone and the hormones produced by the gonads afford particularly good examples of endocrine influence on development, but all the endocrine glands are probably concerned in the regulation of normal growth and differentiation


Adelmann, H. B (1942) The Embryological Treatises of Fabncius of Aquapendente Cornell Umv Press, Ithaca, N Y

Castle, W E (1940) Mammalian Genetics Harvard Univ Press, Cambridge

Child, C M (1941) Patterns and Problems of Development Umv Chicago Press, Chicago

Cole, F J (1930) Early Theories of Sexual Generation Clarendon, Oxford

Ford, E B (1942) Genetics for Medical Students Methuen, London

Goldschmidt, R (1938) Physiological Genetics McGraw-Hill, New York

Gruneberg, H (1947) Animal Genetics and Medicine Hamilton, London

Harvey, E B (1942) Maternal inheritance in cchinoderm hybrids J Exp ,^00/, 91 , 213-235

Huxley, J S (1942). Evolution The Modern Synthesis Allen & Unwin, London,

and de Beer, G R (1934) Elements of Experimental Embryology. Cambridge Umv Press, London

Meyer, A W (1936) An Analysis of the De Generatione Ammahum of William Harvey Stanford Umv. Press, California

(1939) The Rise of Embryology Stanford Umv Press, California

Needham, J (1933) On the dissociabihty of the fundamental processes in ontogenesis Biol Rev , 8, 180-223

(1934) A. History of Embryology Cambridge Umv Press, London

(1942) Biochemistry and Morphogenesis Cambridge Umv Press, London

Nordenskiold, E (1929) The History of Biology Knopf, New York du Nouy, L (1936) Biological Time Methuen, London ^

Roux, W (1888) Beitrage zur Entwickelungsmechanik des Embryo. Arch f Path Anal, u Phys {Virchow's) 114 , 1 13-153

(1895) Gesammelte Abhandlungen uber Entwicklungsmechamk der Orgamsmen Engelmann, Leipzig

Russell, E S (1 J16) Form and Function Murray, London.

(1930) The Interpretation of Development and Heredity Clarendon, Oxford.

Streeter, G L (1942) Developmental horizons in human embryos description of age group XI, 13-20 somites, and age group XII, 21-29 somites Conlrtb Embryol , Carnegie Inst Wash, 30 , 21 1-245 Waddington, C H (1939) An Introduction to Modern Genetics Allen & Unwin, London Walton, A , and Hammond, J (1938) The maternal effects on growth and conformation in Shire horseShetland pony crosses Proc Roy Soc Lond , B 125 , 311-335


Amongst the mdi%iduals of most metazoan species there are certain contrasung chanctenstics which ma> be’classi^d as belonging to either the jntilr oryrww/r sex -It is not possible how_ever, to give a rigid definition of se\ In a broad sense sex ma^ be defined as the power of the individual to produce germ cells (gametes) — spermatozoa or ova The glands le gonads (testis or ovar^) which produce these germ celK are the pnmary sex organs In all vertebrates the tebtes or ovaries develop in the posterior wall of the abdominal cavit) The germ cells produced b> the testes are called spermatozoa (sperms) and b) the ovary ova (eggs) A male may be defined therefore as an individual who normally is orwillbe or has been capable of producing spermatozoa and a female one who normally is, orwillbe or has been capable of producing ova Iri sexual reproduction the fusion of one of each these two sets of cells constitutes the starting point m development of a new individual

Functional germ cells are produced throughout the reproductive life of the human subject In man the process of sperm production spermatogenesis by the testis is normally continuous fiom just after puberty until old age This is also the condition in many primates and domesticated mammals e g , rabbit, pig In some domesticated mammals c g ferret and m many wild mammals eg squirrel and deer spermatogenesis is not a continuous process but seasonal (consult Marshall 1936 Allen 1939 and Asdeli 1946 for details) In the males of those species m vvhich the breeding season is continuous the sex changes are less distinct than in the female while in those species m which there are restricted breeding seasons the marked cyclic sex changes occur m both sexes In the human male there are no cyclic changes, other than phasic activity m the difTcrcnt semtm/erous tubules

The production of ova oogenesis by the ovanes is a cyclic process It is characterized by the formation groitlh and maturation (ripening) of the ovum (or ova) in a vesicle the ovanan folltele hen mature the ovum (or ova) is shed by the rupture of the follicle into thejientoneal cav ity or a recess of this cavity the process is known asoiulation After ovulation the collapsed" follicle undergoes a rapid modification which results in the formation of a temporary endocrine gland called the corpus luteum In the human female the changes just described are regularly repeated in a cyclic manner throughout mature sexual life Thi« periodicity of the female sex function is established gradually at puberty and is continuous until the menopause unless modified by pregnancy or disease

The changes occurring in the testes and ovanes arc under the control oC hormones produced by certain of the ductless glands cspeaally the anterior lobe of the pituitary (page 34)


As has becn stat^ the testes in vertebrates develop on the posterior aWominal wall and m most \ ertebrates including some mammals (c g the elephant and the whale), remain in this position throughout life In most mammals however the testes descend (see page 254 and \\islocki ^933) from this intra abdominal posiuon and come to he cither permanently (carnivores ungulates primates) or temporarily (moles shrews rodents and bats) m a pouch located in the perineal region or the lower abdominal wall . In man the descent is permanent




and the testes are located in a scrotal_sac. They are covered by peritoneum, the tunica vaginalis (page 255), ha\^ their vascular connexions directly with the abdominal aorta and inferior' vena cava, and receive a nerve supply from the abdominal sympathetic trunks. Each testicular duct [vas deferens) passes back through the abdominal wall into the abdomen on its way_to the uiethra The scrotum is probably a device for maintaining the testes at a lower temperature than that of the abdominal cavity, for in most mammals the spermatogcnic tissue of the testes will degenerate at the higher temperature found in this cavity.

There are two elements in the testis of primary importance m reproduction, (i) the seminiferous or convoluted tubules, the cellular walls of which give rise to the spermatozoa, and scattered in the stroma between the tubules the iniersiilial gland tissue for the elaboration of the male sex hormone, testosterone, which maintains the function of the accessory sex organs

and the characteristic male behaviour






j ^ schematic representation of the testis and Its ducts, it shows the course taken by the sperms from the testis to the exterior

The spermatozoa produced in the seminiferous tubules of the testes reach the exterior by a series of genital ducts A schematic representation of the testis and its ducts is given in Fig I. JThe testis is surrounded by a fibrous capsule, the tunica albuginea, whicfTis thickehed'posteriorly to foim the mediasiinum^efisjxora which fibrous septa pass into the interior of the ofgan'and divide it into lobules. Each lobule has "bile or more seminiferous tubules; at intervals, between the tubules, there are groups of interstitial cells. The seminiferous tubules, which are very numerous, are about the diameter of a horse hair and, if uncoiled, are several inches long. The tubules are the essential structural units of the testis and each forms a loop continuous at each end with a straight tubule The straight tubules from all the seminiferous loops open into a network of channels lying in the mediastinum testis and named the rete testis, which is continueiLii^ the effe rent ductules of the epididymis; these in tufn~open into the canal of the epididymis which is continuous with the vas deferens, a thick walled duct which passes from the epididymis through the anterior abdominal wall and then behind the bladder towards the

prostate gland. The vas def erens is joined n^t — itsjCTnunatmn by the duct of the seminal vesicle and the resulting common ejaculatory duct opens into the prostatic part of the urethra


Microscopically the wall of each tubule (Fig 2) shows a basement membrane, lined by a number of layers of cells with spermatozoa either free in the lumen or attached to the inner surface of the epithelium This epithelium is made up of two cell types; tall pyramidal cells (the Sertoli or nurse cells), extending from the basement membrane to the lumen, and rounded cells of several sizes, the male germ cells The latter range from small spermatogonia next the basement membrane through the large primary spermatocytes, and the somewhat small secondary spermatocytes, to the still smaller spermatids more or less embedded in the central pseudopodium-hke ends of the Sertoli cells These spermatids show all stages of metamorphosis into typical spermatozoa (Fig 3).



A number of important changes are rfTectetl dunng ibc process of fonrtalion and maturation of the spermatozoa First, spermatogonia mullipl> b> mitotic diMsion thus assuring a con tinued suppl> of germ cells Second some of these spermatogonia grow increasing setcral times in bulk and are pushed towards the lumen of the tubule to form primary spermatocytes uhich apparently contain enough nutriment to carr\ them through the succeeding stages of maturation at some distance from the basement membrane and the source of nutrition from the capillaries between the tubules Third, the primary spermatocytes prepare for division into secondary spermatoevtes in such a wav that the chromosome number m the latter becomes one half that of the parent primary spermatocyte Flus is called the first maturation or heterotypical division (meiosis) It assures that the sperm cells will contain only the haploid number

Fic 3 — A t^ans^r^sc srcuonora scmmircrous tultuleand intmtitial tissue of the t«us The maturing spcmu are attached bj iheir heads to the Sertoli cells whilst their tails project into the lumen of the tubule ( \rter Sliese in von MollendorfT 1930) x c 330

of chromosomes so that when fertilization occurs the haploid numbei of egg chromosomes will be restored to the diploid number and the new individual will inherit equally from each parent (biparental inbentance)_ Fourth the secondary spermatocy tes quickly divide to form sperma tids thus further m'ulfiplylng the possible number of male germ cells and reducing their size m anticipation of engulfment by the Sertoh cell cytoplasm Fifth engulfment in the Sertoli cells takes place and immediately profound metamorphtc changes begin m the spermatids These changes consist mainly m the loss of almost all the spermatid cytoplasm the concentration of its nuclear material into a dense sperm head and a formation of the sperm neck middle piece and tail m short, the metamorphosis of a simple cell into a specialized motile organism, the functional spermatozoon capable of swimming to an egg and fertilizing This meta morphic stage of spermatogenesis is called spcrmiogcnesis



s^erm Tail


o - A _

‘he adjacem'"^*^ of^

•‘■ahsro^‘^-‘'l^mopIasmTf7h'^'^ *" '=Md and d

  • - % iSInfr"*'® fet'an ™«T>= casfbffffot™ *'

- ■ -“-!!!?«. J?.n.ty, an iiap" “" ™«> opposite " - ' “smonLor flagelium-



grows out through the surface of the cell The centnolcs no\% pass towards the side of the nucleus opposite to that where the acrosome is attached __As-the-centnoles move t owards _ the nucleus the a^l filament is drawn into the cytoplasm of the spermatid A posterior n uclear cap developed from a posterior nuclear bod^ grows around the postenoLparl-ot-ttw— nucieus'ahd’comes intoTdhtacrwith the acfSomic cap' ~Thc antenqr^r pr oximal centnole "TiScomes cldsel>" related to the gramile which lie5~bchind the posterior nuclear ^apjn flielncck repon of the spermatid “ The postenor or distal centrToIe'enlargcs becomes ring shaped and moves away from the'pro'timal centnole along the axial filament it comes to rest at a position which will mark the posterior end of the middle piece of the sperm Most of the mitochondrial granules which are scattered in the cyto plasm of the spermatogonia and spermatocytes pass to Ibrm a sheath for that part of the axial filament between the proximal and distal centnoles of the spermatid as it is transformed into the spermatozoon The remainder of the cytoplasm mitochondria and Golgi apparatus are separated from the ripe sperm and he free in the lumen of the tubule where they degenerate

Sperm Structure

The ripe human spermatozoon possesses a head neck middle piece and flagellum The head consists of the nucleus covered by two caps an anterior cap or acrosome (derived from the Golgi appara tus of the spermatocyte) and a post nuclear cap The two caps meet approximately at the equator In the centre of the head there is a relativ ely large cav ity or v acuole Behind the head is the neck granule which attat-hes it to the middle piece (Gatenby and Beams, 1935)

This middle piece extends from the anterior centnole to the posterior centnole and has an axial filament around which the mitochondrial granules are arranged The axial filament is prolonged through the ring of the distal centnole as the flagellum or tail Recent studies with the electron microscope (Culp and Best 1949) have added some further details of the structure of the sperm (Fig 4) Physiological intcrpreta tion of the morphological details is largely lacking Pollister and Mirsky (1946) using trout sperm demonstrated the actuality of the long postulated chromosome integrity in the sperm head with special staining techniques which revealed the individual chromosomes


The exact length of time necessary for cither spermiogenesis or the whole maturation process is unknown, but it is probable that the diagrammatic

development of a sperm from a pnmary spennatocyte takes only a few matur"no™al hum‘an days hen fully formed the sperms become free in the tubule lumen ipcrmatozoon as seen and are pissed on to the straight tubules rcte testis ductuli cfferentia micr^

the epididymal portion of the vas deferens and finally to the isccndmg amflest ^

and pelvic portions of the vas where they eventually reach the prostatic

urethra and are ejaculated w ith the secretions of the accessory glands as semen ^\ hile the sperms are to all appearances fully formed when they leave the Sertoli cells pliysiologically they appear to be matured further as they pass through the epididyTnis for it is known that their capacity for fertilizing eggs is greater if taken from the tail of the epididymis than when taken from Its head or the testis itself M the sperms mature in the epididymis and vas deferens thev increase in vigour and fertilizing power but if not ejaculated they soon degenerate and are absorbed within the tubules of the cpididyims (Simeone and Young 1931)



7 he human ovaiy possesses an outer cortical and an inner medullary portion (Fig. 5 ) The medulla consists of richly vascularized connective tissue During the child-bearing period the cortex constitutes more than one-half of the thickness of the ovary. It consists of a stroma of

primordial primary


I \

Fig 5 — Schematic representation of the sequence of events occurring m the mammalian ovary during a complete ovarian cycle The development, growth and rupture of the ovarian follicles and the formation and retrogression of the corpus luteum are shoivn

connective tissue in which are embedded the ovarian follicles contaimng within them the developing ova The cortex is covered by a modified part of the peritoneal mesothelium called the germinal epithelium During mature sexual life the ovary is the seat of complex cyclic changes involving principally the ovarian follicles and the germinal epithelium Consequently








Fio 6 A schematic dra^vmg of the relation of an oogonium to the germinal epithelium T ^ cuboidal epithelium covers the ovarian stroma

In B a solid downgrowth of germinal epithelium passes into the ovarian stroma In C the downgrowth consists of follicular cells surrounding a large central cell, the ogonium The ovarian simma c)in>.rc concentric arrangement preparatory to the

oogonium The ovarian stroma shows a formation of the ovarian theca

the histological picture presented by the cortex is always difficult to interpret and sometimes confusing. (The details of the development of the ovary are considered in Chapter XI )

Formerly it was believed that the ova present m the adult ovary were all developed during foetal life. It was thought, in the human, that during childhood many of these ova degenerated but that some lay dormant until puberty when one matured each month and was shed from



the o%ar> There is now good endcnce thato\aintheo\ar> have a short life (E\ans and Swezy 1931) and that the o\a which develop during foetal life degenerate after birth and arc replaced b> oogoma formed b> new proliferation from the germinal epithelium on the surface of the ovary (Latta and Pederson 1944) or from the immediately subjacent stroma W'hcther these postnatal oogoma arise from the germinal epithelium itself or from primor dial ova which have migrated to the neigh bourhood of this epithelium during the earlier development of the gonad has not been definitelv established

The classical description of the pro liferation of surface germinal epithelium into the ov ary is that it occurs in the form of narrow tubular ingrowths {Pj^ug/r s tubes) during the foetal period These arc bchev cd to break up into groups of cells an inner cell of each becoming a primary oo^le while the outer cells arrange themselves around this central oocyte to form a laver offollicu lar epithelium (Fig 6) In the light of our present knowledge three important quah hcations must be made to this classical concept First as already stated there is much e\ idence to indicate that proliferation of germinal epithelium occurs periodically throughout active female reproductive life Second while typical Pflugers tubes are found in certain species (dog seal bear) more commonly solid cords of cells are found In many species irregular masses of cells or even single cells bud off and migrate into the cortev to become oocvtes Third m only a few species do the cells of the epithelial ingroviths clearly take part in the formation of follicular epithelium In most cases indeed the first sign of this epithelium is a layer of verv thin squamous cells directly applied to the oocyte and apparently derived from the surrounding stroma celb These prtmor dial follicles (Fig 7) become primary Jolltcles (Fig 8) when their epithelium becomes cuboidal There is no reason to assume on theoretical or any other grounds that follicular epithelium may not be formed from either germinal epithelium or stroma

Fic 7 — A schematic drawing of a growing primary oocyic of approx diameter 3311 The nucleus con tains a disimct nucleolui I he fat globules are coloured yelloi mitochondria blue and GoIpi apparatus black these structures form the couehe Mtellogene and are situated at one side of the nucleus The follicular cells have become Hattened (This Tig and also Figs 8 and g are based on the work of Aykroyd 1938 ) x c 1 60

Fio 8 — A schematic drawing of a primary oocyte shosmg the dispersal of the miiochondna and Golgi apparatus around the nucleus The fat giobjles (coloured grey) are less numerous The foil cular cells have become columnar and have developed a basement membrane x c 800


T!*e cells destined to become ova, whether derived from the germinal epithelium or not ^ j I ' spond to the spermatogonia and are called oogonia. As these enlarge they become primary compaiable with primary spermatocytes, but they continue to grow to a relatively huge / c as they aie enveloped by the follicular structures, and are commonly spoken of as “ova” aithovK^h 'I.e\ are technically oocytes (primary or secondary) until after the second polar bodv L.viri off As the oocyte grows it accumulates an increasing amount of cytoplasm in nh'ch t*i( tc are a Golgi apparatus near the nucleus, mitochondria forming a crescent-shaped ma-s I a "couche vitellogene” at one side of the nucleus, and, amongst the mitochondria, some fat c'o.)ul.-s (Fig 7) At this stage the oocyte measures about 35 microns m diameter.

rv> Pi-N ZONA




^ ^ schematic drawing of a primary oocyt

showing the further dispersal into the peripher of the mitochondria and Golg apparatus and the remains of the fat globule which are now less numerous Irregular block

S Pellucfda) develoi bcUNcen the surface of the oocyte and the columna follicular cells The ovarian stroma is con "‘""‘"Sed around the follicular cells

A c 73®


POl.l inil AD f/XkJA i CfMi i I^III An

Fig I o — The oocyte has grown to its full size and measures now approx 120/1 in diameter The mitochondria and Golgi apparatus are dispersed throughout the cytoplasm, the zona pellucida is now complete, the follicular cells have multiplied to form a multicellular layer around the oocyte and amongst these cells at one pole of the oocyte a follicular cavity has appeared X c 580

nnrl oocytc increases in size the Golgi apparatus is dispersed through the cytoplasm

firct ^ periphery of the oocyte The mitochondria become scattered

flicnp ^ later throughout the cytoplasm (Fig. 9) The fat globules are also

cells b many disappear until, in the mature ovum, only a few are found. The follicular

them and a homogeneous membrane, the zona pellucida, develops between

unite tn f ^ At first, the zona pellucida appears as irregular blocks which later

nenvitell ^ ^ rf • applied closely to the vitelline membrane of the oocyte, no

lavers space eing piesent (Fig 9) The follicular cells proliferate until there are many

vrannlnsa ^ona granulosa A cavity then appears between the cells of the membrana

or Graa/iari 'foUirlT^ surface of the ovary (Strassman, 1923), thus forming an ovarian,

’ • ne oocyte with the follicular cells, cumulus oophoncus, which surround it,


is at this stage attached b> the discus proltgenis to the deep aspect of the follicle (Fig 1 1) The oocyte now has a diameter of about 120 microns and liquor folltculi accumulates in the cavity of the follicle, It IS presumably secreted by the cells of the membrana granulosa (Shais 1927) As the follicle grows and ripens the stroma cells in contact with the membrana granulosa are differentiated to form the tArm of the follicle (Fig 10) Later (Fig n) these cells of the

theca interna constitute a well defined thecal gland (Mossman, 1937 Stafford and others 1942) Between the theca interna and the granulosa cells there is a delicate basement membrane {membrana propria) A fibrous theca externa can also be distinguished m the human ovary The follicular fluid and the granulosa cells contain the oestrogenic hormone oestradiol, which is

Fic II — The mature ovarian (Graafian) foJLcle The follicular cavit) has become di tended with fluid and now measures approT 6 mm in diameter The oocyte surrounded by some of the follicular cells (cumulus oophoncusi is attached to (he inner aspect of the follicle on lU deep sde The enlarging follicle nor produces a ss elling on ihe surface of the ovary Immedi3tel> surrounding the follicle (he ovarian stroma forms the theca interna or thecal gland X c i

absorbed from the follicle by the blood vessels of the theca mterna There are no blood vessels m the membrana granulosa, it apparently derives its nutntion from the capillaries of the theca interna

The follicles are situated m various positions in the cortex of the ovary Before ovulation can occur the follicle must reach the surface of the ovary As the follicle approaches the surface the cumulus cells become loosened from one another by the accumulation of intercellular fluid so that they separate readily from the follicular wall and, together with the enclosed ovum are shed with the follicular fluid when the latter suddenly escapes at the time of rupture This IS the process of ovulation the cumulus cells round the shed ovum being now called the corona radiala (Fig 26) The actual cause of ovulaUon is still unknown Previous to the rupture



of the follicle there is a sudden increase in the amount of fluid, this is the secondary liquor folhcuh and it may play an important role m the mechanism of rupture and expulsion of the oocyte. During the pie-ovulation period m many mammals, including the human female, the theca interna undergoes an eccentric proliferation on the superflcial aspect of the follicle to form a thecal cone The stroma lound the cone becomes oedematous prior to the rime of ovulation thus facilitating rupture of the follicle Follicular rupture has sometimes been attributed to muscular contraction but the investigations of Claesson (1947) have shown that there is no such involuntary muscle in the wall of the follicle The final pre-ovulation stages have not been observed m man, but m mammals the site of impending rupture of the ovarian surface becomes thin and translucent Walton and Hammond (1928), Markee and Hmsey 936)5 -md others have described this process.

Ovulation is normally limited to the child-bearing period of life, and only rarely occurs before pubeity or after the menopause In most mammals ovulation occurs during the period of oestrus when, amongst other things, the female sex urge manifests itself In primates and man, however, ovulation occurs at a period which probably corresponds to oestrus m everyway except

that the sex desire of the female may


primary oocyte showing the ist maturation spindle of division This oocyte was found free in a large, unruptured follicle (drawn after Stieve) x c 230

not be appreciably stronger. After ovulation the follicle collapses and becomes converted into a corpus luteum (page 24).

At a stage vvhen a cavity has appeared in the ovarian follicle, and the primary oocyte has grown to its full size, important changes occur in its nucleus; these changes are comparable to the changes that occur during spermatogenesis and are knowm as maturation of the oocyte. The formation of the first polar spindle (Fig 12) initiates the first maturation, or 1 eduction, division, the oocyte dividing into a larger cell, the secondary oocyte, and a much smaller cell, the first polar body. In this division the number of chromosomes in each cell is reduced to half (page 19). A second polar spindle is now formed and at this stage ovulation occurs Human ova at this stage of development have been recovered from the uterine tube

by Allen et al. (1930) It was formerly believed (Dixon, 1927) that both polar bodies were formed before ovulation It would appeal, however, that the human oocyte is like that of the majority of mammals in that the first polar body and the formation of the second polar spindle occur before ovmlation and that the second polar body is not separated until after fertilization (Hamilton, 1944) (Fig 27)


The number of chromosomes in human somatic cells is 48 (24 pairs) (Painter, 1923) Evans and Swezy, 1931) This is the diploid number or set of chromosomes The genes controlling sex are carried in a single pair of these chromosomes (the sex chromosomes) and the remaining 23 pairs are the autosomes. In the female the two sex chromosomes, knowm as the X-chromosomes, are similar to one another and differ only slightly from the autosomes in appearance though they possess, among others, the genes w'hich determine sex. In the male,



however the sex chromosomes constitute an unlike pair of which one is an \ chromosome received from the mother, the other the \ chromosome of paternal origin is a small at>’pical (hromosome carrying ver^ few genes of which apparemlv none are actively involved in sex determination The oogoma and

spermatogonia of the gonads are iden tical in chromosomal constitution with the somatic cells of the corresponding sex

During the division of the sperma togonia and oogoma to form primary spermatoevtes or ooc>tes respecincl> the chromosomes split longitudinally forty eight going to each daughter cell (normal mitotic div ision) The chromosomes m the primary spermato cy'tes and oocytes arrange themselves m pairs (bivalents) (Fig 13) In the male each cell has 23 paired autosomes and one pair of sex chromosomes (X\) while in the female each cell has 23 paired autosomes and one pair of sex chromosomes (\X}

During the reduction or mciotic division the bivalent chromosomes separate longitudinall> along the line of the previous pairing so that m the male 23 + X chromosomes go to one secondary spcrmatoc>'te and 23 + \ chromosomes go to the other In the division* of the secondary spermato cytes to form spermatids each chromo some of the reduced number spins longitudinally m the usual way so that two spermatids are produced with 23 d X chromosomes and two with 23 + \ chromosomes Each there

fore contains only half the number or haploid number of chromosomes found m the somatic cell

In the primary oocyte a similar splitting occurs during the reduction division, 23 + X chromosomes going to the secondary oocyte and 23 d- X

  • Although this appears to be a mitotic

division with the reduc^ number of chromo


somes It does not owing to cros mg over (chiasma formation) of the chromosomes result in an identical distribution of the genes to the daughter cells Hence some segretation of the genes occurs at this stage and as Men delian segregation is a result of meiotic di\ iston the division of secondarv spermatoevtes (or ooc tesj must he regarded as a second meiosis not a mitosis

Fig 13 A sell me to show the maturation of the sperma toevte tnd oocylc with the reduction division In the spcr^locyte there are 23 pairs of autosomes and an X+Y pair of chromosomes If the ovum A is fertiliied by a sperm containing an \ chromosome the resultme individual IS a female B if the ovum is fertilized bv I spCTin obtaining a \ chromosome the resulting individual ir a male C The polar bodies each contain "3 autosomes and an A chromosom



chiomosomes going to the first polar body. At the second maturation division, as in the male, a longitudinal splitting of the half number of chromosomes occurs, giving rise to 23 + X chromosomes in the ovum and 23 + X in the second polar body. The first polar body may also divide. All ova are alike in having 23 X chromosomes. A primary oocyte, therefore, gives rise to three or four cells, one of which, the ovum proper, retains most of the cytoplasm, the others, polar bodies, each contain a very small amount of cytoplasm surrounding a nucleus which has the same chromosomal value as the ovum

(Fig- 13) At fertilization the sperm, with half of the somatic number of chromosomes, enters the ovum, also containing half the somatic number of chromosomes. When the two nuclear masses unite the full number of chromosomes is restored It will be seen, therefore, that meiotic division is the antithesis of fertilization; in the former the diploid number of chromosomes is halved while in the lattei the diploid numbei is lestoicd by the summation of the haploid sets from the sperm and ovum.

If a sperm with 23 + X chromosomes unites with an ovum with 23 + X chromosomes the total number will be 46 + X + X, giving rise to a female zygote. On the other hand, if a sperm ^vlth 23 + Y chromosomes units with an ovum with 23 -f X chromosomes the total number will be 46 + X + Y and a male will result. As there is an equal number of sperms with 23 + X and 23 + Y chromosomes and all ova have 23 + X chromosomes the chances of a male or female zygote resulting from fertilization should be equal. In fact, however, the number of males at birth is slightly greater than the number of females in the proportion of 105 to 100.

Genetically the sperm and ovum are both capable of transmitting the characteristics of the race to future generations. Except for the slight chromosomal differences described above, the male and female germ cells must be legarded as genetically equivalent. The zygote contains genes in duplicate derived from the mother on one side and the father on the other (Chapter I).


Allen, E. (1939) Sex and Internal Secretions 2nd ed Bailliere, Tindal & Co\, London.

Pratt, J P , Newell, Q. U , and Bland, L J (1930) Human tubal ova, related early corpora lutea and

uterine tubes Contrib Embryol , Carnegie Inst Wash , 22 , 45-76 Asdell, S A (1946) Patterns of Mammalian Reproduction. Comstock, Ithaca, j >

Aykroyd, O E (1938) The cytoplasmic inclusions in the oogenesis of man ^eits f " rntKr - na ,

Claesson, L (1947), there any smooth musculature in the wall of the graafian follicle’ Ada Anal, 3 ,

Corner, G W (1938) The sites of formation of oestrogenic substances in the animal body. Physiol Rei ,

Gulp, o’ S^and^Best, J W (1949) Morphology of human spermatozoa observations with the electron microscope J Urology, 61 , 446-456 ^ j u ,

Dempsey, E. W , and Bassett, D L (1943) Observations on the fluorescence, birefringence and is oc

of the rat ovary during the reproduction cycle Endocrinology, 33 , 384-401 ♦ „ cpr-nnd

Dixon, A F. (1927). Normal oocyte showing first polar body and metaphase stage m forma 10

polar body Irish J Med Sci , 149-151 , , , TImv

Evans, H M , and Swezy, O (1931) Ovogenesis and the normal follicular cvcle in adult mam Calif Mem, 9 , 119-224 , r

Gatenby, J B , and Beams, H W (1935) The cytoplasmic inclusions in the spermatogenesis o

Jour Mtcr Set, 78 , 1-30 r j ’ 7 SI

Hamilton, W J (1944) Phases of maturation and fertilization in human ova J Anat, on ’ J Hisaw, F L {1925) The influence of the ovary on the resorption of the pubic bones of P

La..., of ova and fo.hc.e f„» ■*.= “if

the ovary of the albino rat as demonstrated by selective intravital staining w

Markee, J E , and Hinsey, J C (1936) Observations on ovulation in the rabbit ^”p! ,^Yran^’ Roy ,

Marshall, F H A (1936) Sexual periodicity and the causes which determine

Mossman, H W. (1937) The thecal gland and its relation to *^'1*80-^20. ^

changes in the ovary of the pocket gopher, Geomys bursarius (Shaw) Am j > 3




Odor D L and Blandau R J (*949) Obser\ations of fertilization phenomena in rat o\a inat Rec 103 580 (ahst )

Painter T b (19 3) Studies m mammahan spermatogenesis II The spermatogenesis of man J Exp Zool 37 291-335

Pollister A \^ and Mirskj A E (l9-(6) The nucleoprotaminc of trout sperm Jour Gen Physiol 30 iot-148

Shaw W (1027) Ovulation in the human osary its inechanism and anomalies J Obst and C}n Bril Emp 34 4C9-480

Simeonc F A and\oung \\ C (1931) \ study of the function of the epididvmis 1 \ Thefateofnon

ejaculated spermatozoa in the genital tract of the male guinea pig J Exp Biol 8 163-171

Stafford W T Collins R F and Mossman H W (194 ) The thecal gland in the guinea pig ov ar> Anal

Rec 83 193- 08

Strassman E (i9'’3l Warum platzt der Follikel’ Arek J Cynak 119 168- 06

Walton A and Hammond J (19 8) Observations on ovulation in the rabbit J Exp Biol 6 too- 04

Wislocki C B (1933) Location of testes and body temperature Quarl Rei Biol 8 38^-396


Female mammals of all species are normally capable of repeated pregnancies during then mature sexual life span Each of these pregnancies is the result of, and the cause of, a complex sequence of cyclic changes in the female which is manifest in her anatomy, her physiology and her behaviour.

In most mature female mammals breeding and non-breeding seasons can be recognized. The duration and frequency of these seasons varies from species to species and can be coi related with periodic changes in the reproductive system. The chief characteristic of the breeding season is the phenomenon of oestrus, or heat, when the female is receptive to the male Oestrus IS essentially a phenomenon of behaviour but it is the culmination of a series of morphological and functional changes in the ovaries and the reproductive tract which are known as the oestrous cycle The changes occui ring at the time of oestrus itself normally include ovulation, an increase in the vascularity^ of the whole reproductive tract accompanied by an increase in the height of the uterine mucosa and of its epithelial cells, growth of the uterine muscle and a rapid proliferation, followed by marked cornification, of the vaginal epithelium

Some mammals exhibit oestrus only once m a breeding season and are consequently said to be monoestrous Other mammals are polyoestrous, that is, they show oestrous behaviour at regular intervals throughout the year or on several occasions during a longer or shorter breeding season In certain mammals domesticity tends to convert a primarily monoestrous condition into an irregularly polyoestrous one

Since oestrus and ovulation occur at approximately the same time, insemination is assured at the most favourable period for fertilization of the eggs. Normally, then, pregnancy follows oestrus and the cycle is not complete until the young have been born and the mother has entered another oestrous period. If for some reason pregnancy does not occur, an oestrous cycle instead of a pregnancy cycle takes place In this case, after a certain period usually shorter than the pregnancy cycle, the female again comes into “heat ” In a sense then these oestrous cycles are abnormal, for the purpose of oestrus is to produce a pregnancy In many laboratory and domestic animals, however, insemination is artificially prevented, and oestrous cycles recur in long sequences.

The phenomenon of oestrus is controlled by the oestrogenic hormone (oestradiol). This IS a steroid, derived from phenanthrene, and is closely allied chemically to the luteal hormone and the hormones of the adrenal cortex, some of which possess similar physiological effects. ' Oestradiol is excreted in the urine as a series of degradation substances (e g. oestrone and oestriol) which have weaker oestrogenic properties. All of these substances together with certain synthetic products (e g , stilboestrol) are known as oestrogens as they can produce oestrous phenomena in spayed (ovariectomized) ammals The origin of oestradiol is not yet definitely known. Some investigators consider that it is produced by the granulosa cells of the follicles but the follicular fluid and granulosa cells contain little if any more oestradiol than the other ovarian tissues Corner (1938) is inclined to the view that the thecal gland produces muc of the oestrogemc hormone This gland consists of specialized theca interna cells of ripCj nearly ripe or recently ovulated follicles (Mossman, 1937) Dempsey and Bassett (i 943 l showed by histo-chemical tests, that sex hormone steroids are absent from the granulosa cells and the follicular fluid but are present m the cells of the thecal, interstitial and mtea glands




The rhythmical chan{,es m the o\ar> constitute the o anan (oogenetic) cyU and those in the uterus ^\hich chiefly m\oKe its lining the endomefmm, constitute the utmn< cycle In the human female though there is no commcing evidence for a breeding season and no uell defined oestrous periods, striking c\chc changes arc also shown b> the ovary and uterus The ovarian cycle is similar to that of rcgularlv poly oestrous mammals The ulenne cvcle includes morphological changes such as arc shown bv other mammals but, m the absence of fertilization terminates in a phase of haemorrhagic destruction of the endometrium known as menslruation For this reason the human utenne cycle is often called the mcns\'nial nde The loss of blood at menstruation is the outward manifestation of one of the phases of the menstrual cycle Menstruation which also occurs in some other primates, is not to be confused with oestrus (see page 33 for di cussion) as is demorntrated by the fact that ovulation does not occur at this time It ism fact known that ovailationm woman normallv occurs about half way between mentrual periods (see page 31) ahhough no obviously greater sexual desire occurs at this time However if pregnancy results from this ovulation then menstrual periods normally do not recur until some time after delivery of the child W ilh rcgularlv repeated pregnancies menstruation might nev er occur again as it is a sequel to the non fertilization of an ovaim The menstrual period and cvcle can then be regarded as basically abnormal, the biologically normal condition being a senes of pregnancy cycles following one another throughout the fertile years of life The human ovanan cycle is probably of the same length as the menstrual cycle (page ah) During the ovarian cycle hormones are produced by the ovary which influence and control the difTercnt phases of the menstrual cycle


The proliferation of oocy tes and the shedding of an ovaim or ov a, as described on page 14 arepcnodic and together with the recurrent formation of the corpus lutcum (after each ovulation) and the accompanying changes in the interstitial tissue and theca! gUnd constitute the ovarian cycle This cycle is repeated throughout the reproductive life of the individual With the exception of the ovum or ova which will be shed at the next ovulation and some ova in primordial and primary follicles all the maturing ova developed m a single ovanan cycle will degenerate and, with their follicles become ctreUc In the succeeding cycle these arc replaced by the growth of persisting primordial ovanan follicles and by the proliferation of new primordial oocytes The number of ova present m the ovary increases towards the end of the menstrual cycle probably as the result of the removal of the inhibition due to the corpus lutcum of the previous ovarian cycle (sec later, and Evans and Swczv 1931)

The growth of the follicles is gradual up to the pre ovulation stage when a rapid increase vn size occurs In the human subject muaWy only a sin^Ie/olhclr grows to maturilv and ruptures in each cycle the oth«r follicles undergo atresia, which may occur when they are small or at later stages even when they irc almost fully developed IMien a follicle becomes atretic, its ovum undergoes hyaline swelling and fatty degeneration the folhciilar cavity collapses the granule a cells degenerate and disappear and arc ultimately replaced by connective tissue and the theca interna cells may become transformed into a group of intentitial gland cells

There w a cy die production of hormones by the ov iry during the grow th of the follicle As the npcning follicle nears maturity its theca interna cells take on the character of an endocrine gland both cy tologically and m their relation to their v ascular supply This is the thecal gland Its cells probably produce the oestrogenic hormone which is taken up by its blood vessels This hormone causes changes m the accessory sex organs i c the uterus the vagina and utenne tubes and also influences the production by the pituitary of the gonadotrophic hormones The oestrogenic hormone is responsible for the phenomena of oestrus m lower mammal

After the rupture of the follicle and the formation of the corpus lutcum the cells of the latter produce a second hormone called progesUroiu This hormone also exerts its influence upon the accessory sex organs bringing about the progestational changes in the uterus which are discussed on page 27




As stated earlier, after ovulation the ruptured follicle collapses and its wall becomes folded, the granulosa cells hypertrophy to almost three times their original diameters, become polyhedral in shape, develop a yellowish pigment (the carotinoid, lutein) and become vascularized by ingrowth of vessels from the thecal gland to form a corpus luteum (Figs 14, 15 and 16) ; their nuclei, however, except immediately after ovulation, show few mitoses. The modified granulosa cells are called luteal cells. In some mammals there is an increase in the number of luteal cells m the early stages of formation of the gland due in part at least to mitotic division of young luteal cells According to some investigators (Solomons and Gatenby, 1924, and Shaw, 1925) the glandular cells of the theca interna also increase in size to become “paraluteal” cells These may be persistent thecal gland cells which in most mammals persist for a few days as a zone round the recently ruptured follicle, but which have usually completely disappeared by the time the embryo begins to implant in the uterus In some species true luteal cells are added to the

Fig 14 — A schematic drawing of the corpus luteum The blood vessels and fibrin are in red, the fibrous trabeculae blue

periphery of the corpus luteum by continuous dilTerentiation from the immediately surrounding stroma cells (Mossman and Judas, 1949). For a review of the literature on the corpus luteum see Harrison (1948).

The fate of the corpus luteum in women, but not in all mammals, depends on whether or not pregnancy follows ovulation. In the absence of pregnancy a corpus luteum (spurium) of menstruation, with a functional life of approximately fourteen days, is formed. In the event of pregnancy, the corpus luteum becomes a corpus luteum (verum) of pregnancy The granulosa derived cells of the corpus luteum produce the hormone, progesterone, which in the human is necessary for successful maintenance of the earlier stages of pregnancy Removal of the corpus luteum from the human female during these early stages of pregnancy results in abortion, and m some mammals (e.g , rabbit, rat and goat) removal, even m late stages of gestation, terminates the pregnancy. Hartman and Corner (1947) have shown that the corpus luteum of pregnancy m monkey may

be removed as early ty-fifth day

without disturbing t y* In the

human species and in the chimpanzee progesterone is excreted as

■ the urine


The functional life of such a corpus luteu

1. Stage of Hyperaemia. There with the rupture of the follicle The granu colour During this period the glandular ce easily distinguished. Between the theca an many blood vessels but the granulosa cells

2. Stage of Vascularization.

the ingrowth of blood vessels from the vascu is observed and may be so abundant as to fill th


nto t









The cells of the membrana granulosa become lutcahzcd, \acuohtcd and polyliedral m shape The stroma cells of the theca imade the area of luteahzed cells and form a \ascularized connectise tissue (Figs 15 and 16)

3 Stage of Maturity The luteal cells enlarge and become dislinctl> sacuolated and am blood present in the ca\it\ is absorbed The inner or luminal margin of the corpus luteum often shous a delicate la>er of flattened cells uhich are modified luteal cells (Solomons and Gatenb), 1924) The blood sesseU increase in size and become more numerous and lhrou<'h them’ the hormone enters the blood stream The stage of maturit> is reached tuo or

Tic 15 — Photomicrograph of a section of a human corpus luicum approximately 48 hours after ovulation X 130

Fic iC — \ high power schematic view of the rec tangular area of Fig 14 sho\ mg the detailed histolofiy of the corpus luteum Blood vessels are earned amongsl the luteal cells and thecal gland cells b> the fibrous trabeculae x c 200

three days before the onset of the next menstrual period The mature structure may be easily recognized on the surface of the o\ary as a yellowish projection surrounded by a hypencmic aret and it may constitute one third or even one half of the \oliimc of the ovary The mature stage of the corpus luteum corresponds to the premenstrual or luteal phase of the endometrium 4 Stage of Regression Before the onset of menstruation the corpus luteum diminishes in size loses its vascularity becomes fibrotic and the Juteil cells show fatty de generation Baily degenerative changes are always to be seen in the corpus luteum during menstruation Later hyalimzation of the luteal cells occurs and cicatrization of the fibrous tissue eventually obliterates the lumen This fibrouc remnant of the corpus luteum is called



a “corpus albicans ” The rate of regression varies considerably but eventually any given corpus albicans disappears.


If pregnancy occurs the corpus luteum increases in size, but remains essentially similar in appearance to the corpus luteum of menstruation up to the end of twelve weeks of pregnancy. The luteal zone, however, is broader and there is usually a greater amount of fibrous tissue along Its inner border. The cavity may become filled with a straw-coloured fluid Further, the visible cellular changes m the distribution of lipides are prolonged and intensified during early pregnancy (Papanicolaou et al , 1948). In the human subject the corpus luteum of pregnancy is considered to remain active until the end of the fourth month, when regressive changes begin It can usually be distinguished until after parturition

The persistence of the corpus luteum of pregnancy beyond fourteen days is believed to be due to the production by the foetal tissues (e g., the developing placenta) of substances, possibly oestrogenic hormones, which prolong its life. The functional replacement of the corpus luteum m those species in which the organ degenerates relatively early m pregnancy IS also believed to be due to the vicarious activity of hormones from the placental tissue replacing that of the corpus luteum.


This cycle of changes in the human female and closely related primates has as its most stiiking character the periodic flow of blood from the uterus As this flow has a monthly (28 day) periodicity in most women it has traditionally been called the “menses ” The length of the menstrual cycle of different individuals is, however, subj'ect to wide variations The most common length is 28 days, less frequent are cycles of 25, 26, 27, 29 or 30 days or longer, but a 21 day cycle is not uncommon Variability in the length of different cycles may be shown in the same individual. The first day of haemorrhage, 1 e , menstruation, is taken as the lirst day of the cycle The duration of the menstrual flow is subject to wide variations in different women, and, from time to time, in the same woman Fluhman (1939) gives the average duration as 3 to 6 days ’


The menstiual cycle is characterized especially by phases of growth and degeneration in the endometrial tissues, but there are also less marked cyclic changes in the uteime tubes, uterine muscles and vaginal epithelium If pregnancy occurs, the cyclic function is interrupted by a long gestation period Following parturition, other adjustments are established, associated

with lactation, which if it is continued, usually inhibits for a variable time the resumption of the cyclic changes

It IS customary to subdivide the endometrial cyclic changes into four phases — {a) menstrual, {b) post-menstrual , {c) interval or prolifer ative', and (rf) pre-menstrual, pre' decidual or secretory If the menstrual cycle IS considered in its relations to the ovarian cycle, there are only two phases, afolh' cular phase and a luteal or progestational phase which terminates with menstruation (Fig. 24).

1 r


  •  » v-s l' ^





^ view of the endometrium on the 5th

menstrual cycle Menstruation had just ceased (The magnifications of Figs 17 to 21 are all approximately X 20 ) 1

® power view of the endometrium on the 6th day

of the menstrual cycle (after Schroder in von Mollendorff"




The First or Follicular Phase This includes the post phases It js characterized b> a period of growth which begins s metnum following the previous menstruation The growth phase to the action of the oestrogenic (follicular) hormone which in a 28 da> menstrual c^cle produces lU ma-cimal effect during the first 14. da\s During the first few dd>s of this phase the regeneration of the surface epithelium which began to take place before the menstrual flow had ceased is completed Frequent mitoses ma\ be rt cognized stK*ru especnli> m the epithelium of the glands which lengthen com c hut remain straight and tubular The endometrium at this period is thin (Figs i7A and B), with an average thick ness of o 5 mm to i mm the stroma is compact and the ncvvlv regenerated epithelium becomes cuboidal Dating the later part of the follicular phase, which continues until ovulation or in the non occurrence of ovoilation for a st» tu comparable period there is eontmued growth of all parts * “

of the endometrium (Fig 18A) The surface epithelium becomes columnar as does to a lesser cMcnt, that of the urcK > glands (Fig aaA) there is usually some serous secretion “ " 1 he endometrial stroma now siiows a division into a denser

menstrual and proliferative vith the repair of the endo of the endometrium is due


superficial layer stratum (ompaclum an intermediate more loosely arranged layer stratum spongtosum and a deep layer, stratum basalt (Figs 18A and B)

The Second or Progestational Phase This includes the second half of the menstrual <ycle le the secretory and menstrual phases The accompanying changes in the endometrium follow one of two possible courses ^^hen ovulation occurs a corpus luteum develops and the endometrium is changed gradually into a true progestational state due to the action of progesterone probably associated with a synergic decrease in the amount of oestrogenic hormone As a result the endometrium increases m thickness up to 5 or even 7 mm , it shows active secretory changes and persists m this state until mcmtru ation If ovulation does not occur no progesterone is pro duced as a corpus luteum is not formed the folJich s undergo atre la and the secretion of the oestrogenic hormone diminishes the result is a gradual but mcrcasinj, degenera tion of the endometrium without an intervening secretory phase

The progestational endometrium following noimal ovulation is soft velvety and oedematous (ic water logged owing to the distension of the intercellular spaces by fluid) and usuallv pale in colour because of the oedema It can now be more readily div idcd into the stratum com pactum with densely packed swollen stroma cells the oedematous stratum spongiosum which surraunds the dilated glands and the sirilum basalc which shows no hvpmrophy or oedema (Figs 18B and l9^

The superficial parts of the glands tend to be straight and narrow, whereas the deeper parts arc tortuous ard

Fic 18 — A lower power new of the endomelrium on j jib day of the men strualcycJc The endometrium shows a separation into stratum compactum and straium spongiosum After O I ear> and Culbertson (1928) By thecouriesv ofSurg G}nee and Obilet B A lot er po\ er view of the endometrium on the 16th day 01 the menstrual cycle The glands are here slightly dilated (after Schroder in ton MollendorfT 1930)



markedly dilated (Figs, 19 and 23), The convolutions of the glands are often so marked that in longitudinal section they present a serrated appearance (Fig. ig) with the gland cells often collected into tufts During the early part of the luteal phase the epithelium of the dands IS columnar with the nuclei in the peripheral part of the cells, leaving a clear basal zone which IS filled vith glycogen (Fig. 22B) In the later part of this phase the epithelium becomes cuboidal with irregular, frayed outline, the cytoplasm apparently melting away as a secretion into the lumma of the glands (Fig 2 qC). The secretion is rich in mucin and glycogen The

Fig 19— a lower power view of the endo.


® dilated and shov

>pical hacksaw” appearance (aftei Schroder m von Mollendorff, ,930)

Fig 20 — A lower power view of the endometrium on the 28th day of the menstrual cycle The endometrium shows oedema and blood has been extravasated under the epithelium (modified after Bartelmez, 1933)

the amount of r i resemble those of the decidua (page 67), with an increase m

arteries leadino- ^ eucocytes and large mononuclear cells are numerous The small

become verv tr> from the basal zone through the spongy to the compact zone

case is from^an^e^d”^ known as the spiral arteries (Fig, 23) Menstruation in this

n ometrium which has undergone progestational hypertrophy.

,, menstruation

of the ovaries and^ be considered as the outward and visible sign of the periodic activity

of the tvnp , ^^^®t™ntion which occurs from the progestational endometrium

the t)pe just described is that which is characteristic of mature sex life.


Some authontito difTercntiate between the Upe of bleeding which occurs from an endo metnum which has not been subjected to the influence of the luteal hormone, i e from a uterus m a woman in which o\ulation has not occurred m the c>clc concerned (inos-ular c\cle) and menstruation following normal o\ulation Shas\ (i934) Schroeder (19*3) emphasize that the two t>pes of bleeding should be regarded as separate and distinct, and the\ would restrict the term menstruation to bleeding from a progestational endometrium \ccording to them bleeding in the absence of o\uhtion should be considered as pathological No\ak (1921) Bartelmez (1937) and others regard menstruation as a periodic physiological bleeding from the uterine mucosa and hold the opinion that it ma> occur in the absence of ovailation The bleeding m both o\ular and ano\ailar cycles occurs following a growth phase and is degenerative in character being preceded b\ oedema and accompanied by necrosis of the endometnum Apparently there is no good reason for not calling both these types of uterine bleeding men struation regardless of whether a follicular or progesta lional endometrium is imolNcd Menstruation without ovailation is the exception in mature sexual life, but it is however common in girls at puberty and at the commencement of menopausal changes and in the former it may be the explanation of their rcimve infertility *


During menstruation the superficial layers of the endometrium are shed The basal layer remains essen tially the same throughout the menstrual cycle and from It the regeneration of tile endometrium after menstruation occurs

Preceding the onset of menstruation there is some shrinkage of the endometrium due to the diminishing oedema Bartelmez (1933) regards the oedema as a manifestation of the pre^ravid sta^e produced by the progesterone

Immediati ly before the actual bleeding period there 18 superficial congestion of the endometnum accom panicd by dilatation of the veins and some necrosis of the superficial cells This is followed b\ a leaking of blood from the superficial \ cssels to form lakes under the surface epithelium (Fi 20) some of this blood escapes into the uterine cavity The endometnum may show liulc or no loss during the first day while on the second day inmanyr cases the endometrium is shed down to the basal layer (Fig 21) There is considerable variation m the amount of tissue lost Normally n is not shed en masse but rather crumbles away m small pieces This tissue loss may be ascribed to destruc tion of the capillary bed The circulation m the endometnum appears to be controlled during menstruation to prev ent excessiv c blood loss There is ev idence that some parts of the stratum spongiosum persist throughout the menstrual period and are reorganized during the repair following menstruation (Bartelmez J931)

o a I — \ lovi view of the endo itieirmm on the first day of the m nsttiia\ cvctc The superficial lasers of the endometnum have been shed (modifierl after Batielmer 1911'

• It IS V ell known that adolescent pre mariial intercourse though frequently praciised in onmitur only rarely rwults m pregnancy although €>vert menstrual rhenomena are well wiabhshcd fsee M F Ashlev Montagu adolescent Sterility —Qvari Rn B,ol jom VoJ 14 t>o t .-io anrT.;,- ^ tv. ’ 1 '



Towards the end of menstruation the endometrium may be reduced to o 5 mm, in thickness, 1 e , to approximately one-tenth of its maximum thickness. The denuded endometrial stroma is completely and rapidly re-epithelialized from the epithelium of the stumps of the glands which lie retained in the basal layer. The loosely arranged cells of the basal layer multiply to form the stroma of the endometrium after the circulation has been re-established The regenerative processes begin as early as the third day of menstruation, and proceed very rapidly. Papanicolaou (ipSjii) states that the restoration of the epithelium is brought about by the transformation

of the endometrial stroma cells into an epithelial layer. Markee (1940) has been able to observe the changes


‘•.it ) } I* iJ’A

V *'<. V* ^







Fig 22 —A A high power view of the epithelium of an uterine gland on the loth dav of the menstrual cycle The

celS’ epithelial

B A high power view of the epithelium on the 1 6th day of the menstrual cvclc.

C A high power view of the uterine gland on the 25th day of the menstrual cvclc The secretion from the cells has p.^sed into the lumen of the glands w Inch IS now distended The epithelium IS columnar with irregular edges

Schroder m von

Mollcndorfl 1930 )

which occur in the endometrium during the menstrual cycle in the macaque monkey by transplanting small pieces of It into the anterior chamber of the eye

Sources of Menstrual Flow. The menstrual discharge is derived from the endometrium above the level of the internal os. The cervical mucosa takes no part in the menstrual bleeding, nor does the mucosa of the uterine tube. The discharge itself consists of blood, epithelial cells and detritus resulting from degeneration of the stroma and normally does not clot. There is great variation in the amount of blood lost during the menstrual period ; the average amount in the healthy woman is 50 to 60 c c It may, however, be double or treble that amount without being considered abnormal (Frank, 1929)

Cause of Menstruation. The cause of menstruation has received considerable attention but so far has not been fully explained. - In a general sense it is brought about apparently by the withdrawal or decrease of a complex hormonal influence, probably both ostrogemc and progestational hormones, which is necessary if the conditions existing in the endometrium at the end of the cycle are to be maintained

There can be little doubt that the changes occurring m the uterus as the result of the action of the oestradiol and progesterone are a preparation of the endometrium for the reception of a fertilized ovum In the absence of fertilization and implantation the corpus luteum degenerates and menstruation occurs The persistence of a functional corpus luteum and therefore the presence of progesterone after the 28th day of the menstrual cycle prevents the degenerative changes from occurring in the endometrium There is evidence, however, that oestradiol continues to be produced during the luteal phase of the menstrual cycle and that it acts synergically with progesterone (Hisaw et al., 1937). It may be that, at this period, oestradiol helps to maintain the activity of the corpus luteum. In the normal non-pregnant cycle the amount of oestradiol present is minimal just before menstruation and there is an accompanying cessation of progesterone production It is probably the simultaneous withdrawal of both of these hormones that brings about normal menstruation There is evidence, however, that





the rcmo\al of either ocstradiol or proi>estcronc alone maj precipitate bleeding (Corner, 1P38, Hisa\% and Creep 1938, and Phelps, 1916) M has been stated carhrr, uterine bleeding may occur in the absence of o\ulation Phis phenomenon can be explained b\ the decrease m the amount of oestrogenic hormone towards the end of the cycle

The actual menstrual haemorrhage is probably due to changes m the arteries winch supply the superficial two thirds of the endometrium (Bartclmez, 1933 and Markec 1940 and 1948) There is a period before mcnstniation during which the arteries increase m length and become much coiled (Fig 23) This is followed by stasis of the blood and later b\ \asoconstnction of the arteries which leads to anaemia and csentually necrosis of the superficial parts of the endometrium, which arc sloughed off Tlic vessels

for a short time dilate allowing haemorrhage into the endometrium to occur the blood loss being controlled by a mechanism which is not yet fully understood (Schlegcl 10^5 and Rcvnolds 1947) It must also be pointed out that a phenomenon closely rescmblin^ menstruation occurs in certain New ^\orld monkeys m which coiled endometrial arteries arc completeK absent or very poorly developed (kaiser, 1948 and sec Ramsev 1949 and Okkels for discussion)

TIME OF OVULATION Ovulation m the human female as in most mammals is spontaneous that is rupture of the follicle (or follicles) occurs indepcndcnil) of copulation In certain mammals (e g the cat the rabbit the ferret) however ovulation only occurs if mating takes place In most mammals whether ovulation is spontaneous or induced follicular rupture occurs in close relation to oestrus In woman and mam of the primates there is no distinct oestrus and there has long been confusion on the time in the uterine cycle at whtcli ovulation occurs particularly in us temporal relationship to menstruation Recent research lvowe\er has greatly clarified ideas both on this problem and on the intimately related one of tlic penod of fertility in the human female

It is now generally licld that ovulation occurs not more than once in a single ovanan cycle though occasionally more than one ovum is shed

This view IS not accepted by all investigators Flius

Samuels (1937) and St, esc (.9,4) hue adduced eMdence that osulal.on mi) ocrur scleral times m a single c)cle (supplementac) or paracvdrc oiulltion) Man) other imestigators base faded to substantiate these uorkers claum for as Siegler {1944) has summarized the general attitude their data arc too meagre to uariant practical consideration In vieu of the vast amount of evidence m us support the view that ovulation normalK occurs once in a cycle Will be accepted m this book

The determination of the precise time in n fejvcn cycle at which ovuhtion will occur or has occurred is a problem of the greatest importance Unfortunately aviilablc methods do not permit of complete assurance but it has been shown that ov ulation precedes menstruation y a penod of time usually 14 days which vanes withm narrow limits m most women That



IS, in a 28-day menstrual cycle ovulation occurs at about the imd-pomt. The more or less fixed relationship between a given ovulation and the next menstruation is determined by the lunct.onal length of life of the corpus luteum resulting from that ovulation In general, regression of the corpus luteum, and the associated decline in the production of progesterone, commences about 10 days after ovulation and menstruation itself begins 4 days later. While the time leiationship between ovulation and the immediately succeeding menstruation is ‘‘impressively regular” (Papanicolaou et al , 1948), the time relationship between any given O /ulation and the preceding menstruation is much more variable This variability is the result of an inconstancy in the degree of development of the ovarian follicles at the time of the preceding mensti nation and of differences in their rates of growth and the effects of competition amongst them General hormonic and psychological factors may also be involved.

In view of the considerable importance of the problem the methods that have been used to determine the time relationship between ovulation and menstruation have been summarized

1 Allen et al (1930), who have recovered living ova m washings from the uterine tube, and who have studied the young corpora lutea, believe that ovulation takes place on or about the 14th day of the menstrual cycle The recovery of ova is the most convincing method of demonstrating that ovulation has occurred

2 Knaus (1929) has evolved a method for determining the time of ovulation which depends on the non-reactivity of the uterine muscle to pituitrin in the presence of a functional corpus luteum This change occurs apparently 12 days before the expected succeeding menstrual period, 01 15 to 17 days after the first day of the preceding period Assuming that it takes about Uso days to establish the activity of the corpus luteum, and for the uterus to become lefiactoiy, Knaus concludes that ovulation occurs at about the 14th day if the cycle is of 28 days, or in any case about 14 days before the beginning of the succeeding menstrual cycle. The phenomenon of non-reactivity of the uterus to pituitrin does not occur in anovular cycles.

3. The inspection of the ovaries of women has given results which point to the period of the middle of the cycle as being the most likely time of ovulation.

4 Venning and Brown (1937), who have been able to recover the luteal hormone from uiine, have shown that there is an increase in the amount after ovulation, 1 e , about the 15th or 16th day of the cycle This increase is maintained until just before menstruation.

5. Changes in the histological appearances of the endometrium at different times in the menstrual cycle The histological appearances of the progestational phase of the endometrium are specific, and if they are present it is assumed that ovulation has previously occurred. This method is used clinically m the investigation of sterility when portions of the mucosa are removed by cuiettage during the pre-menstrual period

6 Bun et al (1937) have shown that there is a relatively enormous rise in the electncal potentials across the pelvis just before the time of rupture of the ovarian follicle

7. Papanicolaou (i933®) found that in one-third of women examined there is a definite cyclic change in the vaginal smear He is of the opinion that there is a stage in the cycle in these cases where red cells are present, and other changes are found that are indicative of ovulation Unfortunately, the method is not as decisive m women as it is m other mammals

8 Farris (1946 and 1948) has shown that the urine of sexually mature women, during a period of about four days before ovulation, contains a gonadotrophic substance which produces ovarian hyperaemia m immature rats following subcutaneous administration This substance is presumably of pituitary origin Investigations by Corner et al (1950) indicate that the urinary’’ rat test of Farris gives the time of ovulation in a high proportion of cases with sufficient accuracy to be of clinical value.

g.^ It has been shown by many investigators that the normal body temperature has a cyclic variation throughout the menstrual cycle


CVCLIC CHANCrS IN HU IIMAII (.INIIAI IKACl At about the mid point in i cycle «f20d\y< therein \ Ifmcrim of the nciiii d l( iii|trinhMi

follo^^cd by a rise which pcnisls until luotliysl)crorrincmtruition«lirnlliriri-«m iin n lowi lidi

until menstruation ceases Hus is followed 1 >> a second rise svlutli persists to llir mid pultil of the cycle Such cyclic varntion in temperature does not mciir in <i\ iiie( loniirrd woiiirii or in women after the menopause Ihc evidence siipi>orls the (Oiitriition tint tin mid lyilr nse in the basal temperature coincides approximately with oviilitioii (lot dist iissjoii sri Martin 1943 Tarns 19^8 )

The evidence accumulated from the almc sources {khiiM to the time of oviil ilioii us hrmj the 14th (ii) day previous to the cxpccicil date of onset of the next inrnstni ilu n It most Ik stressed however that there is much variation from vvoman to worn m, due m p irt to difli irmrs in the length of the menstrual cycle, cspeciiHyin die diir ilion of the folio ill ir pli tse in womni with a regular 2&-day cycle the evidence however, seems tlrirly to lodu ilr lliil oviditloii occurs at aI>out the middle of the cycle lor a discussion on vinilioiis in rrlihon lo the o-called safepenod secFlcckr/a/ (tyjo), I apanicolaoii r/a/ i-otnrr fl al


Oestrus IS that special penod in the sck cycle <if nuny fern dr mimmd ilotmy whldi ihe female is vsalling to receive the male It is ass^Kivtcd with 1 ntirnher of < ft tni rs in the prnif il svaicfn eg rapid npeninj, of the ovarian follicles, f^rowth irid fK-dem 1 f<f the menu ind comification of the vaginal mucr/sa This last chance c in l>e flemonstr ifed in the hvini' unim tl b\ talung vaginal smean In women, however there is no well defined iK-slroiit f>f millin' penod In the pait much confusion was caused h/ atternpls lo rorrelite the rhirn'es fhil occur at oestrus in lower ferms with the chan es th it r<eiif in women it men ini iiir n

In raanv unjulates carnivores and rwlenfs the t>^Ufxi cycle e m l^e snlKlivided mfo more or les.1 dutmet phases —

«( \n erviTj-i phase during which the generative or; ms ire rjiiiesrenl md rfien atrophic \h, a /rs-siet r u.f phase dufin^ whieb there it grr miIi md prolifer »lion fif (ifi< yfes in l^e o -an and eroAth of the insues of the repTwluetive rr/an , m'lre esjK-ri dly the end' meirmm et t-e irenis ard the ntcosa cf the va«ona thi 1 f'lf' ^ed hy ft} an fKl/f n (heii)

phase* dL-ir2 er soen after which cvailation veurs, and at which there rrn/ le* (e g , m ihe bi ch sTcht haer'errha^'e /Vfri the en-o-r ed endemetfium Oe-rnis i f' IfoA'ed hy j re; riirey if luccesa^J nat.rg takes place er h a perjrxl ef / m'nptfinnr/j, m seme ^inirn^l , jf ihe rrMlmg has fcern sterile If rating net crnirrrf! anether peneiej nrir^tirut frll'\/s In ammal whe-e tfia 1- cr^I ls short it is i: lall/ calVd <i 7 -< rj. f.ur if ler?* r^t r^itru , althnj/h ihi Ut.r' t— r is rj- V icf equent' ii ed

I wxj f rmc-l thcT -ri-t {i^t fy-irr,u e-penap/ in the fueh wa cemyrtrrtHeff mer IT wer-r- srer r h>eth cerditer there 1 Heed.r'e ffrm the uterus In seme wrnir- t e— ra/ fee leue- ah,e'er>rsl pam ( iri/^Wrere’ j ^ sli'»ht feijee rrhey^,

and-ar-iij a fclord-,^-eJ s'. e'-a-je at aVn* t‘-e r-ide'V ef the rer trual eyrie s her. e /ul^nen a kre s-u to eren- Tr s w'* Jes efhley,dh« he'en re-emded h/ serre ^utferiftei

s- c-rca-a'-Ie w d- re hae-er-^i-r- at ey-fn in t‘-e htreh The eerpns lufeum herrnere

er-ser-re ^ ser-r m s' <31 err'er-e-rlf g-e ^tr ry rn, rer with

tha u-i^ I- f^e >■ i-nar Ir-'a e j- fi-e ser>-rr* h ' el the ner tru d r,r(r- ff p-r r see; I'ee* ‘i-acrre' en et po- e'rer-*- ,r /i e-tiH her' 1 hieh e enf.i dl/ • r rt rsterr d h errevh e

-eci-rniha r-e- r-ant en in mar are* tre h

•C a-r* t'*r de-’— e— i rj j-e^ fererne/ if re

■‘•irhcernr-ir h. no' reeurrerr e. ^ ir

e‘'i re* ifee* pee je* p'-e r•e** mersf- 1 .t r e ,n ef** err'rrre e u




It IS now know^n that the cyclic changes occurring in the ovary are under the control of hormones produced by the anterior lobe of the pituitary. These hormones exert little or no direct action on the uterus or vagina, but act mainly through intermediation of the ovaries. 1 hei e are, apparently, at least ttvo gonadotrophic hormones produced by the pituitary which act on the ovary (Evans et al , 1933, Fevold, 1937, Creep el al., 1940); a follicle stimulating hormone (FSH) and a luteahzing hormone (LH) (Fig. 24), The FSH is responsible for the control of the development of the follicle and for oestradiol secretion. The early growth of the follicles can hn\\e\. ■ occur independently of the anterior pituitary hormones (Smith and Engle, 1927) LU c^'i nols ;Ke luteahzation of the follicle after ovulation and possibly also the production of ' il liujii' 'p Theie is, however, evidence for the activity of a third gonadotrophic e d p lb *' opine hoimone (LTH, and probably identical with prolactin), which he sti ohif for progesterone secretion by the corpus luteum. Either FSH or


Fig 24 A graphic presentation of the relationships of the anterior pitmtaiy, the otarian follicle, the corpus luteum and the endometrium

Menstruation is represented as occuriing fiom days one to four during which most of the endometrium IS desquamated This is followed by the follicular phase of growth which is brought about y ne action ot the follicular stimulating hormone, FSH, of the pituitary on the growing follicle IS IS o lowed by the luteal phase during which the luteahzing hormone of the pituitary acts on shown '^^'(Afler^'s”\i ^ degeneration of the corpus luteum of the previous cycle are

LH may separately produce ovulation, the optimum condition for ovulation is probably prepuce of a synergic balance between the concentrations of the tw'o hormones in the blood (Hisavv et al., 1937) If the anterior lobe of the pituitary is removed the ovarian cycle ceases. Injection of extracts of the pituitary or the implantation of grafts into immature animals causes ovulation (Zondek and Ascheim, 1927).

T e factors responsible for the cyclic production of the gonadotrophic hormones are numerous and are not yet fully understood The ovarian hormones themselves appear to have a reciprocal effect on the hypophysis, thus an increased production of oestradiol by the ovaries may inhibit production of FSH which will lead to a diminished secretion of oestradiol, wnth, in turn, t le diminution of the inhibitory action. That the gonads have an action on the hypophysis IS also shown by the histological changes occurring m the latter as the result of spaying and castration when charactenstic involuted cells (“castrate cells”) appear in its pars anterior A nerv'oi^ mechanisrn appears also to be a factor in control of the sex cycle This mechanism involves the hypothalamic nuclei and the hypothalamic-hypophyseal pathways There may



be an mhercnt rhythmic control b> the hvpolhalimus but in man> \crtcbrnc. (bird, ferrets, etc see Bissonnettc 1932 nnd 1935 Marslnll 1936) cm ironmental conditions, for cxamp e h«ht ma% act reBcxI) b% \\a> of the optic ncrxc and tract and the Ii>pothahmic centres The nervous mechanism of control ofthccjcle however tssubsidiarv in importance to the hormonal for the pituitarv can still exert its controlhnt, action when its nerves have been sectioned or even when the gland itself has been transplanted {Creep t93G)

arl\ c< rpora lutea I Jour Obsl Cm 1 rtit/ranr t( the luiman ulrriis Coni ib

Rov Sor Lo d


Allrn I Iran J I Nc» ell Q, L and IHind I J (igioi Human tubal o\a relaled c and uterine lulies Conltib h.inhrttl CurBrfre /njl lla«A 22 45-7^

Ilartelm a C W (1931 1 1 e human uterine muerus menibranc dunm: fneniiruation 1 »

21 0i3 t)43

- 1^53 liutnlncral studira ot the menitruatin? n

{■mb) I Carntgit Inst 24 141-1P6

'>91< Menstruation Dmwl Re 17 aR 7

Bissonneit 1 H (19311 Moriifieation of mammilian jenual evdrs reactions r f f rrrij (Puinriiis sultans) nl Ixih sexes lo electric lit;ht add d after dark m \ scml*er and December J rc

Biio a 33r

___ 193, \todifita\ion of nsammatian vexsial carles tV Oelss of oesttui and induction of a in f nnlc ferrets Is reduction of ini nsiu and diiraii n of dail) beht p fiodi sea on 7 Fjp Riol 12 31^ a *>

1 urr H S Muss Iman L K llarion 1) S an I KelK \ I* (1937 Ho 1 clnccorrelatciofhumanosulation lelt 7 /jo/ 0 rf \ftJ 10

Corner C t\ '1931!' Fxp rimental nienstrustirn like 1 1 nl nt; due to 1 r rnione depnsaiion Im J TAif 124 I I

(arris F J and C^rn r C \\ Jr 1190 Tl e daime of c siilation and other > sarian cri e« b\ hisio*

I ?inl xaminai on in comparison iih th I irris im i"ttr J 04 t Cinte 59 ^14-311 Demises 1 W snd Bassett D L ti9|3' Ot ersati os on ftuorejffTife 1 irefrincence and hi U chemisirv o1 nt sars diinnc reproduciise c>cle hnlMtinolo r 33 3114-401 I anj H M Simpson M I and \usim I K (1933' lurlher siu 1 rs on the li\popli>seal $ul stance 511 int;

nrrea d ?< nadolrophic elTecis s I en combine I s iiU | rolan J Fj{ \trj 5 b jIS-jFi — — and Ss ers O (1931) Oso^enesis and the normal follicular r\c! in adult rnartunaM'i tfrm Lnt lain 9 M9-tUU

larrii T J antCI \ test f r deierminmg tl e time of ©vsilation and concepti n in ssnin n li»<r J Oitl

52 >4 •' 7 .

sulaiion I s

— — iiOtOfl The prediction < f the da> of bui la Amrr J Obsl Cyntt 56 347-351

h9t£!4 Temperature compared s»iih rat

liJOf 138 /o-5fl

(esold H I 11937 Ih gona lotrophic liorm 5 93-103

Fleck S Snedeker F F and Rock J (1940) Ibe comracepuic ivfc pen d a clinical ttiuK

J \UI 223

t St fie predictio C Id Sft,

rat lest as ernf rmetl bs fifts cancepiions of human ovulation J iner Mtl lUrbouf on atfi/jji r Riol ^

\m rni;

J Ufl 223 100,-1009

Huhman 1 F (I939t vlensirual Di orden Saunder* I hiladetpbu Frank R T (19^9^ The female s x hormone Ihomas Sprin^ield III

Creep R O ti93b; Functional pituitar> grafts in rats Iroc Sot Ijefirr Diot Med 34 754-75^

\an D\ke H H and Chow il I (1940) Separation in nearly pure form of luteimsin^ (iiucmilial

cell stimulating) and follicle sumulat ng (gimctogcmc) hormones of pituitarv gland 7 tli I Cfiem 133 280-290

Harrison R J (igjO) The desclopmenc and fate of the corpus luteum m the \crlebraie sen s Biol Rev 23 29G-331

Hartman C G (19)) Studies in the reproduction of ll e monkey Macacus (I iihecus) rhesus i ith special reference to menstruation and pregnancy Cont ti Fmb rot Carnegie In i Hash 23 t-iGl — — and Corner G SS |ig47) Uemosal irf the corpus luteum and of the osanes of the rhesus monkey during pregnancy Ohsersations and cautions Inaf Ret 98 539-546 ’

Hisaw F L Creep R O andFevoId H I (1937) Tl e effects of oeslrin proi,e$tm coml ination on the endo metrium vagina and sexual skin of monkess 4ni ^ Inal 61 483-^04

Hisavv F L and Creep R O (1938I The inhibition of utenne bleeding with esira bol and progesterone

and associated endometrial modifications rndoennolo t 23 1-14 Kaiser I H ^I948| Newer concepts of menstruation Inter J 04tt Gyaet 56 io\7-tof:

Knaus H (ig 9) Fine neuc Melhode zur Bestimmung des Ovulationstermines ^enlralbl' fCyn 53 2193 “'‘"jIj., m'" ">

11940) The^morphological^and ^endocrine basis for menstrual bleeding Progress in Gynecology

Grune and Stratton Inc New \ork - U948' Morphological bas s for memtntal bleeding BhH \ T draij Med gods

24 253-268


F H A (1922) The physiology of reproduction Longmans, Green & Co., London, and Ed

— . Sexual periodicity and the causes which determine it Phil Trans Roy Soc , Land , B 226 , 423-456

' P T. V1943) Detection of ovulation by the basal temperature curve with correlating endometrial

MjdiCj Amer J Obsl Gynec , 46 , 53-62

■ . - tr, H \V , and Judas, I (1949) Accessory corpora lutea, lutein cell origin, and the ovarian cycle

n I’.ic Canadian porcupine Am J Anal, 85 , 1-40

1021' Menstruation and Us disorders Appleton, New York Okkf-ls, H (^1050') The vascular anatomy of the adult human uterus In Modern Trends in Obstetrics and

'-o)og> (Bowes) Butterworth, London.

Till' I 1 an^ Culbertson, C (1928) The form changes in the human uterine gland during the menstrual ■ ' Surg Gynec and Obsl , 46 , 227-239

1 4 tine .laou, G N (1933a) The sexual cycle in the human female as revealed by vaginal smears. Am. 7 Anal, 55 519-616

— 0933 ^) Epithelial regeneration in the uterine glands and on the surface of the uterus Am J Obsl

G}n, 25 , 30-36

Frant, H F , and Marchetti, A A (1948). The Epithcha of Woman’s Reproductive Organs Commonwealth Fund, N Y.

y< Joj Doris (1946) Endometrial vascular reactions and the mechanism of nidation Am J Anal, 79 ,

1 ) 7-197

\ 1. 'sl (1949) The vascular pattern of the endometrium of the pregnant rhesus monkey (Macaca

inulatid) Contnb Embryol , Carnegie Inst Wash, 33 , 1 13-147 Reynolds, S R M (1947) The physiologic basis of menstruation a summary of current concepts Journ Am Med .dwoc , 135 , 552-557

Samuels, J (1937) Die Fruhdiagnose der Schwangerschaft Munch med Wcehnschr , M, 1323-1327 and 168116S8

Srhheel T w ('1945 Arterio-venous anastomoses in the endometrium in man . 4 c/a 2lna/ , 1 , 284-325

" 19131 Lber die zeitlichen Beziehungen der Ovulation und Menstruation Arch f Gynak ,

' ‘ i-tj

] Die vveilbhchen Genitalorgane In Handb d mikr -Anal d Menschen (v Mollendorff), 7 , Pt i ' nngei Berlin

N I92j) The '.'li.on of ovarian function to menstruation J Phys , 60 , 193-207 -oji Ovulation ' 1. .nenstruation Brit Med Jour, 1 , 7-10 ' P F and Enc'e ’ ’ (1927) Experimental evidence regarding the role of the anterior pituitary

ir 1 le developrr^w 1 legulation of the genital system Am J Anat , 40 , 159-217

Solomons B and Gate i \N' B (1924) Notes on the formation, structure and physiology of the corpus

laleum of man *' and the duck-billed platypus Jour Obst Gyn , Brit Emp , 31 , 580-594

" ') FI ),'j 44) Pat che ovulationen Kungl Svenska Veten-akad, Hand, 21 , 1-19

\ nning, E H,andBro..', J S L (1937) Studies on corpus luteum function I The urinary excretion of sodium pregnandiol giucuronidate in the human menstrual cycle Endocrinology, 21 , 71 1-721 Zondek, B , and Aschein S (1927) Hypophysenvorderlappen und Ovarium Beziehungen der endokrinen Drusen zur Ovarialfunktion Arch f Gyn , 130 , 1-45


There are great difTerences m the size of the mature unfertilized egg m difTcrent \ertcbrates (see Chapter WI) With the exception of monotrcmcs the eggs of mammals are small and contain httle deutoplasm oik) , i c the> ate miolecithal In the cuthenan mammals the diameter of the shed egg lies between 8o/i and 150^1 The eggs however often show distinctive characteristics m the appearance of the cytoplasm or vitellus In some mammals the parts of the vitellus are arranged m such a way that the ovaim exhibits distinct polaritv one half is rich m cvtoplasm and poor in deutoplasm the other is nch in deutoplasm and poor in cytoplasm (Fig 25) The polar bodies arc extruded at the cytoplasmic pole and the retained nuclear material the female pronucUus, lies nearer to tins pole

Fertilization is the act of fusion of the male and female gametes to form the zygote In mammals as m birds and reptiles the union of the male and female sex cells takes place wiihm the bodv of the female In these vertebrates the semen is deposited m the female genital tract bv a special intromittent organ the penis the act accompanying the deposition of the semen is called coitus or copulation The actual deposition of the seminal fluid in the vagina IS tnsmwalion

G '>3 — \ teciion of a ferret zygote with eccentrically placed pronuctei at approx 47 hours after insemination The polarity u evident by the presence of a cytty plasmic crescent which is more darklv stained


Shortly after ovulation the human ovum surrounded by the corona radiata passes into the uterine tube (Hamilton 1944 Figs 26 and 27) Soon however the corona radiata cells degenente and separate from the zona pellucida Allen et al (1930) Lewis (1931) and Pmeus and Saunders (1937) have recovered living unfertilized human ova at this stage In the living ovAim the zona pellucida appears as a translucent and apparently structureless membrane

The diameter of the ovaim including the zona pellucida varies in the human ova which have been described The Lewis ovaim had a mean diameter of 148^. in other unfertilized ova described the diameter varied from 115/1-134/1 In the Lewis ovum the vitellus completely filled the zonal cavity and had a mean diameter of 136/t m some ova the vitellus does not fill the zonal cavity so that a periuttlline space is present The vitellus is surrounded by a structureless vitelline membrane In the living state the vilcUus is slightly yellowish in colour with a clearer outer zone and a darker central part On account of the refractilc nature of the vitellus it is impossible in the living human egg to sec the nuclear apparatus


In the act of fertilization the male and female gametes {i e sperm and ovum) fuse together and form the zygote In man as m other mammals fertilization normally occurs m the ampulla of the uterine tube Before describing the process of fertilization the transport of the spermatozoa and ovum must be discussed




Fig 26 — Photomicrograph of a living human ovum surrounded by the corona radiata recovered from the uterine tube X 480 (Original ) (Reproduced by the courtesy of the j of Anat )

Seminal Fluid. The

seminal fluid, or semen, is a complex mixture derived mainly from the testes, the seminal vesicles and the prostate gland The bulbo-urethral gland and the glands of the urethra provide a small amount of pie-ejaculatoiy lubricating fluid The fluid in man, m a normal ejaculation, amounts to about 3 c c , and contains 200-300 million spermatozoa, In the semmifei ous tubules the sperms are non-motile, as they are passed along the vas deferens by the ciliaiy and muscular activity of this duct they become mature and, after ejaculation, motile, the tail performing an undulating movement which piopels the sperm foiuard The secretions derived from the accessory glands help to activate the sperms and at the same time provide a carrying medium for them Examination of the semen has become important in the study of fertility The numbei, motility and abnoimalities in Size and shape of the sperms are all of importance in assessing the possible responsibility of the male partner in sterility (For literature and discussion see Weisman, 1941, and Joel, 1942 )

Transport and Viability of the Sperms. In mammals, It IS kno\vn that sperms pass very rapidly into the uterus and fiom it into the uterine tubes (Hartman and Ball, 1930, F^rker, I93U Florey and Walton, 193 ^’ Chang and Pincus, 195O They are rarely found, hoive\ er, in large numbei s in the uterine tubes It IS partly by their own activity, the undulatory movements of their tails, that the sperms pass into the cervical canal and the cavity of the uterus They are able to swim against the current produced by the ciliary action of the utenne



rpithclmm Talmc\ (1C117) and Scgm ind Vineux (1933) that the uterus ma% ha%e a sucUn^ action dunng the orgasm u hich rm> dnxs the sperms into the ccrMca! canal omm howcser uho do not experience an orgasm during coitus seem to be as fertile as women who react normalK \ficr coitus in the rat Rossman (tq37J has shown that sperms arc aspirated mtn the uterus and passed rapidK along it 1 j\ its muscular contraction

Fate of the Sperms in the Female Genital Tract There is reason to behcNc that human sperms like those of moit mammah, ha\e a short Ide in the female genitil tract Most of the sperms are dead withm a peiwsd of four da\-s fCaia 1936) and m most mammals

ihes base lost their fertilizing power e\cn earlier Hammond 1923! * There is a correlation between sperm acti\it\ and abiht\ to fertilize the Q\aim but the greater the motility the more rapid will be the loss of fertilizing power Tlic sertetions found in the vacma dcstcos the fertihrint, power of the sperm after a short period Uithin narrow limits the more acid tiie secretion the less motile arc the sperms alkalmils on the other hand increases their motihts hence the shghth alkaline

^ ft rr t'.A

uicnne secretions are fwourable for sperm transport

Transport of the Ovum through the Uterine Tube The o\um when extnided from the osars soon enters the ^nfundthulum or funnel of the uterine tube apparently vsashed into It fay currents m the peritoneal and follicular fluid created In the actniu of the cilia of the infundi bulum and its fringe of fimfanac The latter are applied to the osarian surface ^\^cstman 19371 The tulie IS lined with cihatnl epithelium scattered throughout which arc some non ciliated cells (Corner 1932J At the time of osailation the musculature of the tube is contracting rhythmically The o\um is passed along the tube fas the muscular contractions and bs the acti\ ity of the cilia There

• The length ol life of ihe sperms afier rjaculaiion can b» increased by suuabfe condiUons of storai; (llammcnd 1941 1 This IS of considerable imporiancc »n ihr rrenomin of sicxkbre dint; It has been st osw m the bone lhai sperms ha\ a longer fertilizing life (up 10 6 daysi than in most mammais Insomebais apparenOv (Hartman Uimssti 19441 th sperms can surMsemihcutmis during the winter and are capable of fertilizing an enum in the folios in? spring Sod rwall and Blandau (*9411 have shown that the fertilizing capacitt of sperms araiiciallt Wi mmattd in todents is e\cn less than is usually thought The fig ires they gv\e are 6 hours (moiisci to 30 boui irabbit) Chang (19 ,i> has shown ihai the fertibzinsr ptw er of sperms is increased by a sojourn in the uterus

Fro "8 — Sections of cleas age stages of the egg ofrhegoldenhamscer Cnctlutaumius x 640 \ CentralU placed pronuclei R First cleat age spindle C a celled stage D Second cleavage spindles at right angles to each other iReproduced from Boyd and llamil tor in Physiology of Reproduction b\ kind permission of Messrs Longmans Green



IS no definite knowledge of the time taken by the human ovum to traverse the tube, in lower mammals it is usually three to four days and presumably it is the same in the human subject the time required appears to be independent of the length of gestation and of the size, length and calibre of the tube

It IS now established, m the human subject, that an ovum from one ovary can pass to the opposite uterine tube, when the tube of the same side has been removed (transperitoneal migration) Whether the ovum actually migrates across the peritoneal cavity, or the tube reaches across to embrace the ovary at ovulation, has not been settled. For discussion of migration of the ovum in mammals see Boyd et al (1944).

Viability of the Ovum. It is known, from animal experiments, that the mammalian ovum IS only capable of being fertilized for a short time after ovulation. Hammond (1941) has shown that if fertilization does not take place within a limited period after shedding (rabbit, 12 hours, guinea-pig, q 6 hours; ferret, 30 hours) the ovum undergoes degenerative changes. If fertilization occurs, the ovum, now called the zygote,'*' undeigoes cleavage during its passage along the uterine tube (Fig 32)

Fertility. Fertility depends upon

Fig 29 — Photomicrograph of the 2-cclled stage of the human zygote x 500 (Reproduced by the courtesy of Drs Hertig and Rock )

the co-oidination of many different processes and upon the normal functioning of both male and female reproductive organs Whether fertilization in the normal mature female results from insemination depends on (i) the time interval between insemination and ovulation, (2) the length of time that the ovum remains fertilizable, (3) the number of spermatozoa reaching the uterine tube, (4) the time taken by the spermatozoa to reach the ovum in the tube, (5) the length of time during Avhich the spermatozoa retain their fertilizing power, (6) other factors in the semen which influence fertilization One of these appears to be the presence of a sufficient quantity of the enzyme, hyaluronidase (Rowlands, i 944 )'


In an earlier section, fertilization was described as the fusion of the male and female gametes. In the majority of mammals so far studied m this respect the oocyte, surrounded by the corona radiata, is shed from the ovary with the first polar body extruded and the second maturation spindle formed. It is at this stage of development that it is penetrated by the fertilizing In all but one or two of the relatively small number of mammalian species investigate , an probably in the human subject (Hamilton, 1944), the spermatozoa meet the ovum in the cepha ic portion of the uterine tube Only one sperm of the many deposited in the female genital trac IS required to fertilize the ovum Additional sperms may be found attached to the zona pelluci a or may even be found in the perivitellme space (Pincus, 1936), but they take no part in future development

The sperm can enter the ovum at any point on its circumference In many mammals t e entire sperm is known to pass into the cytoplasm of the ovum After the entry of the the second polar body is extruded and the chromosomes which remain in the ovum themselves into a vesicular nucleus, the female pronucleus (Figs 25 and 28A) The vi e

  • Theoretically, the term ovum should not be used after the commencement of p" human

embryology, however, the term is loosely applied up to the late blastoeyst and early pre-somite stag



shrinks so that a distinct pernitellmc space is present The head of the sperm undergoes changes after it enters the ovum, it swells and becomes transformed into the male pronucleus (Fig 28A) A human pronuclear stage has been described b> one of us (Hamilton 1949) The middle piece and tail persist for a short time later the\ are no longer \isib!e apparently becoming absorbed b> the cytoplasm of the osaim

After the head of the sperm has become detached from the middle piece and tail it probably rotates through 180 as it passes towards the female pronucleus which now approaches the centre of the ovum The two pronuclei soon meet in approximately the centre of the o\'um (Fig a8A) A centrosomc, which is possibly derived from the proximal centriole of the sperm, now becomes distinct It dmdes into two parts each of which is attached to a pole of the spindle which now makes its appearance (Fig 28B) At the same time each pronucicus resolves Itself into Its chromosomes and the nuclear membranes disappear The chromo somes of both pronuclei arrange themselves on the spindle and each splits longitudinally the resulting halves passing towards the cenlrosomes Opposite the equator of the spindle a circumferential furrow develops on the surface of the zygote it deepens until the cytoplasm is divided into two giving nse to a two cell st ige of the embryo or ovum (Fig 28B and C) Each of the daughter cells contains an equal number of paternal and maternal chromosomes (Chapter II) The polar bodies persist for a variable period of time m the penvitelline space (Lewis and Hartman 1933, and Hamilton 1934) but they eventually degenerate and disappear

The main results of fertilization are the restoration of the diploid number of chromosomes the determination of the sex of the zygote and the initiation of cleavage It must be realized, however that while with the exception of the sex chromosomes the egg and sperm are equivalent m chromosome content there is an immense disparity in the amount of cytoplasm contnbuted to the zygote from the two sources It is because of this that the influence of the egg on dev clopment is greater than that of the sperm The cy toplasm of the oocyte is organized before fertilization and in many species shows striking polarity Hence during cleav age cells which differ qualitatively are produced and these differences are of cytoplasmic rather than of immediate chromosomal origin

Parthenogenesis In many invertebrates and lower vertebrates it is possible to stimulate the oocyte to undergo cleavage in the absence of spermatozoa (Loeb 1913 and Morgan 1927) This artificia] parthenogenesis (to be carefully distinguished from artificial insemination) may result m the development of mature partheno^enetic adults Parthenogenesis of course occurs normally in many invertebrates In mammals there is some evidence that the ovarian egg may attempt to undergo cleavage but this never results in organized development (Pincus 1936) though it mav be

Fic- jO —I holographs of living eggs of the macaque monLcs stage &— three cel! stage C— four cell stage D — five cell stage stage F —eight cell stage ( \fter Lev is and Hartman 1933 ) of tf e Carnegie Institution of Washington y c *00

A — two-cell E — SIX cell Bv courtes)



involved in the pathology of teratomata Pincus (1939) has succeeded in stimulating development artificially in ripe unfertilized rabbit ova which, when transplanted to the uteri of uninseminated females, developed into parthenogenctic individuals


Cleavage consists of a rapid succession of mitotic divisions resulting in the production of a progressively larger number of increasingly smaller cells, called blastomeres. Although the cells increase m number during cleavage this mechanism is not a growth process m the usual sense of this term as there is no increase in protoplasmic volume during its occurrence. In fact the protoplasm decreases in amount as the result of metabolic activity. The principal effects of cleavage are three in number Firstly, there is a partitioning of the protoplasm of the zygote amongst the blastomeres. Secondly, an increased mobility is conferred on the original protoplasmic mass with consequent facilitation of the morphogenetic movements and rearrangements of later development. Finally, as the fertilized ovum, even m mammals, is much larger than the average adult cell size, cleavage results progressively in an approximation in size of the

developing cells to that characteristic of the definitive cells of the organism. In this respect cleavage can be considered as a mechanism for the automatic re-establishment of the cell size normal foi the species concerned

Cleavage is classified in several different ways (see Chapter XVI) In descriptive embryology it is usual to classify the process according to the pattern of the divisions This pattern is largely dependent on the amount and distribution of the deutoplasm stored in the ovum. As there is only a small amount of such material in the true mammalian ovum there is little impedance to cell division so that cleavage, in eutheria, involves the whole ovum and results in the production of a numbei of equivalently-sized cells. Such cleavage is total (01 holoblastic) and equal.

Only a few human cleavage stages are known Hertig and Rock (1950) have described a two-cell stage recovered from the uterine tube (Fig 29) In addition they have described stages (probably abnormal) of eight, nine and twelve blastomeres which resulted from in vitro fertilization of human ovarian ova (Rock and Hertig, ^94^) It IS necessary, therefore, to refer to other mammalian material for a description of the details of cleavage Many accurate and detailed descriptions of the cleavage of the ova 0 mammals, m both living and fixed material, are now available The present account is base mainly on the monkey ovum, as described by Lewis and Hartman ( 1933 ) the species Macacus rhesus since this species is more closely related to the human than any other form m which cleavage has been studied The account, however, has been supplemented, where necessary, by references to other types

The first cleavage division has not been observed in the monkey, but it is probably menihona as it is in most mammalian eggs A two-cell stage was recovered from a monkey 292 after ovulation It was cultivated in vitro and remained in the two-cell stage for 7 hours cells were oval and lay parallel to each other (Fig 30A) They were unequal in size as is olten the case in two-cell stages of mammals. The cytoplasm was uniformly granular except in the neighbourhood of the nucleus, where it appeared as a clear area, and at each side of the nucleus the cenlrosphere and yolk material could be seen The nucleus of each cell became ^nvisi about hours before the next cleavage; this corresponds to the onset of the prophase. -1

Fig 31 — A photograph of the living morula of the macaque monkey (After Lewis and Hartman, 1933 ) By courtesy of the Carnegie Institution of Washington X c 300



distinct polarity described in man> mammalian two cell stages was not recorded The division at the two cell stage v^as dichotomous but the cells did not divide s>nchTonousl> At this stage as at subsequent stages the larger cell divided 6rst. so that a three cell stage was found (Fig 30E) The smaller cell of the two cell stage then divided and the cleavage planes of the two cell stage vs ere approximate!) at right angles to each other so that the cells of ihe/our cell stage, consisting of tuo larger and two smaller cell, la) crosswise (Fig 30C) the larger cells of this four cell stage divided before the smaller cells so that stage:, office sve seien and eight cells viere found (Fig 30H, E and ?) The axes of the spvndles which divided the cells were again probabl) at right anjes to each other m each pair of cells as in most mammals but this was not observed for the monke) The cells at the eight cell stage were so arrai^ed that the four celb derived from the larger cell

Fic 3 — \ sehcmaiic representation of the de\elopm»nt of the ovanan follicle its growth maturation and rupture Successive stages m the passage of ihe ovum into the tube and its fertilization subse quenV development and imptaniation are depicted (Based on DicVinson ) (i) Unsegmented Doe>le

at the ■’nd maturalion spindle (3) Fertilization (3) Eccentrically placed pronuclei and polar bodies (4) 1st sp ndle of division (5) Two-cell stage (6) Four cell stage (7) Eight cell stage (81 Xforula (9) and (10) Free blastocyst m uterine cavitv (11) Earl) phase of implantation (approvimately at the seventh day after ovTilation)

of the two cell stage were at one pole and the four cells derived from the smaller cell were at the other pole The cells of the eight cell stage in mammals continue to divide at different rates so that stages with nine ten etc to suteen cells are found At about the sixteen cell stage (Fig 31) the ovum of the monkev reaches the uterus and is known as the morula It consists of a group of

centrall) placed cells {inner cell mass) completely surrounded b) a peripheral la)er of cells (the future trophoblast) A morula w as recov ered from the uterus of the monkey 96 hours after ovoilation In the morula all the cells were of similar appearance, but subsequent development shows that the process of dcav age has brought about segregation of embry onic material so that it possesses a mosaic pattern despite its apparent uniformity of structure This segregation permits future differentiation as a result of potentialities whKh are inherent m the cells but these potentialities may be modified by environmental conditions (Chapter Vlll)



Le%vis and Hartman (1933) give a provisional estimate of the duration of the different cleavage stages of the eggs of Macacus rhesus as follows ; —

1 - cell stage . from ovulation to 24 hours after.

2- cell stage . „ 24 hours to 36 hours

3- 4-cell stage „ 36 „

5-8-cell stage . . ,,48 „

9- 1 6-cell stage . „ 72 „

There are no data of the precise time taken by human ova to reach the uterus, nor is the interval between ovulation and implantation known. A scheme showing the presumed developmental stages during the descent of the human ovum is given m Fig. 32. In the macaque monkey the blastocyst begins to implant m the uterine mucosa (Chapter V) on the ninth day after ovulation 54 and 55). Hertig and Rock (1945) have shown that the human blastocyst is already partially implanted between the seventh and eighth day after ovulation





Fio 33 A section of a g-day macaque blastocyst Four types of cells may be recognized, the blastocystic trophoblast, the polar trophoblast, formative cells of inner cells mass and endodermal cells, the zona pellucida has disappeared and the blastocyst IS ready to be implanted (Re-drawn after Heuser and Streeter, 1941 ) x c 240

Fig 34 — A three-dimensional reconstruction o the same blastocyst as in Fig 33 ^ ®

flattened endodermal layer is spreading in 0 the inner aspect of the blastocystic tropho as (Re-drawn after Heuser and Streeter, 194* ! X c 280


For descriptive purposes the early development of the embryo may conveniently be subdivided into stages It must be emphasized, however, that normal development is a continuous process and that this subdivision is for descriptive purposes only The account which follows IS an attempt to provide a synoptic picture of early human development and is based on t e published descriptions of a large number of human embryos (see Appendix)

In most mammals, the morula, at the time ivhen, or just after, it has passed into the uterus, undergoes modifications which are chiefly of a physical character Fluid passes from the uterine cavity through the zona pellucida and outer cells of the morula, which act as a dialysing membrane, into the intercellular spaces between the centrally placed inner cell mass and the outer ce s ^Vith the increase in the amount of fluid the spaces on one side of the central cells become confluent forming a single cavity, the blastocoele, and the outer cells become flattened (Figs 32, 33 and 34) •



\s a result of these changes the inner cell mass comes to be attached etcentncall> to the inner aspect of the outer flattened cells \%hich are now called the trophoblast The embryo at this stage of development is referred to as a blasloeyst At about this time m most mammab and, as Hertig and Rock hav e recently found (Fig 35), also in man the zona pellucida disappears, thus permitting the trophoblastic cells of the blastocyst to become attached to the uterine epithelium (Chapter V and Figs 54 and 55) ^ . ov

The trophoblastic cells proliferate rapidly and invade the maternal tissue (Figs 3b and 5t5) In the monkey and presumably in man cndodemial cells segregate from the blastocoehc surface of the inner cell mass and become grouped into a single layer — the pnmary endoderm (Figs 33 34 and 36) The remaining cells of the inner cell mass which are at first intimatelv related to the overlying trophoblast constitute the columnar embryonic ectoderm (Figs 36, 37 and 38) As these latter cells arc the source of the embryonic ectoderm and in later stages, of the secondary mesoderm and may give rise to further endodenn, they have been called the formatiie cells (Heuser and Streeter 1941) Between these ect^crmal cells, which become arranged into

Fio 35 Photomicrograph of a secoon of a human bIastoc>st X 600 (Reproduced by the courtesy of Drs Ileriig and Rock J

Ftc 36 — \ section of a 7I day human ovum partially implanted m secretory endometrium X too The embryo is represented by the rounded mass of cells just above the trophoblastic mass and beneath the thin membranous pomon of the collapsed blastocyst wall (Reproduced by the courtesy of Drs Rock and Hertig )

a flattened disc, and cells {ammogemc) which arc denved from the covering trophoblast a cavity appears— the ammolic cautj (Figs 36 37 and 58} At the penphery of the disc the flattened amnjogenn, cells are directly continuous with the embryonic ectoderm In the youngest known implanted human embryo the amniotic cavniy has already appeared (Figs 36 37 and 58) Its further history is considered on page 78

During the period of the formation of the ammotic cavity the endoderm is concerned in the formation of a second and initially larger cavity — the pnmary jolk sac In the monkey blastocyst the endodermal cells spread beyond the maigins of the ectodermal disc (Fig 34) and by extension and proliferation come to line the whole blastocyst thus forming the pnmary yolk sac This yolk sac later becomes separated from the inner surface of the trophoblast by extra embrjomc mesoderm In the 7! day human blastocyst (Fig 36) the endodermal cells already form a single laver on the uterine cavity aspect of the fonname cells In slightly older human blastocysts (Figs 37 38 and 58) a primary yolk sac has appeared and a considerable amount ofloose extra embryonic mesoderm separates it from the inner aspect of the trophoblast (Figs 37, 38 and 58) The human yolk sac in these stages has a roof of cuboidal endodermal cells m contact with the



columnar embryonic ectoderm. The latter together with the cuboidal endodermal cells constitute the bilammar embryonic disc which is approximately circular in outline From this disc all the tissues of the embryo proper are derived The endodermal cells of the yolk sac roof are directly continuous at the edges of the disc with a layer of very thin mesothehal-hke cells m contact with the extra-embryonic mesoderm. This layer has been called the, e.'.ocoelomic, or Heuser's, membrane The precise nature and origin of the cells of this hning layer have not been determined They may differentiate in situ from the inner cells of the primary mesoderm or they may possibly be derived from the disc endoderm by migration as occurs in the macaque monkey (see page 75 for discussion) Whatever the nature of these cells, the cavity enclosed by them and the disc endodei m was called the exocoelom by Streeter (Fig 38) We,

pl'otomiciogiaph of a human implantation of estimated age 12 days (Hertig and oc ) t he syncy tiotrophoblast has irregular laminae containing some maternal blood e cytotrophoLiast consists of an inner irregular shell The -trophoblast at the abemP° ^ Ihtle differentiation and at one point is not yet covered with uterine

epi le lum The inner aspect of the cytotrophoblast is lined with mesoderm which is TOn ense on its inner aspect to form a membrane, the exocoelomic or Heuser’s membrane le em lyo consists of a thick layer of columnar embryonic ectoderm and a thinner layer o irregu arly arranged polyhedral cells, the embryonic endoderm, the latter, at its edge, is on muous 'vith the exocoelomic membrane The space lined by the exocoelomic memf ^ endoderm has been called the exocoelom by Hertig and Rock, in the present text le erre to as the primitive yolk sac A space, the amnion, lies between the mesoderm and embryonic ectoderm X c 100

however, shall call it the primary yolk sac (Fig 37). It ^vlll be seen that the cells of the primary

cuboidal cells in its roof (embryonic disc endoderm) , and flattened mesot e la - 1 e cells enclosing the remainder of the cavity Soon the cuboidal endodermal cells m a oca ize area near the future anterior margin of the embryonic disc become columnar This area of columnar endodermal cells is Xh^rochordal plate (Fig 39) ; it confers a bilateral symmeUy ^ ^ 6isc by establishing an antero-posterior axis The flattened cells limng the

remain er o t e primary yolk sac are concerned with the early nutrition of the embryo and they ° ^o'^tri ute to Its structure with the possible exception of early blood cells (Chapter V )

• ^ separating the primary yolk sac from the inner aspect of the trophoblast is ca e

the primary^ extraembryonic mesoderm (Fig 38), it is absent m the youngest known human embryo (Fig 35) but m slightly older ones fills the space between the trophoblast externally and e amnion an primary yolk sac internally This precociously developed primary extra-embryonic


mesoderm m man and the higher primates appears to be derived from the trophoblast Such a derivation of extra embryonic mesoderm is unlike that found in most other mammals vvhere all the mesoderm arises from the ectoderm of the posterior part of the embryonic disc in the region ofthe Cnniitue xtreai (see Chapter XVI) .

In shghtK older human embryos the primary mesoderm has increased in amount and terms a loose mesenchymatous reticulum'^ the magma nhadatt Later small ca\ itics appear in the primary mesoderm these enlarge and become confluent to form the extra embryonic coelom except in an area v\ here the amnion remains attached to the trophoblast The mesoderm is thus separated into a layer lining the trophoblast and one covenng the sides of the amnion and the yolk sac

Fic 38 — \ schematic representation of Fig 37 based 00 a reconstruction b> Heriig and Rock The relationship of the embryo to the surrounding endometrium is shown X c 130

The primary mesoderm lining the trophoblast and covenng the sides of the amnion is called the extra embryonic somatopUurtc (panetal) mesoderm The part of the primary mesoderm covenng the yolk sac is called the extra cmhiyonic sphnchmpUunc (visceral) mesoderm * The membrane formed bv the extra embryonic somatopleuric mesoderm and the overlying trophoblast is known in mammals is the chorwn It corresponds to the serosa of reptiles and birds At this stage of development the amnion with the attached primary yolk sac is suspended from the inner aspect of the chorionic sac by that mass of primary mesoderm into which the extra embryonic coelom has not extended (Figs 39 and 40) This portion of the primary mesoderm will later become the connecting stalk

  • It IS important to realize that the extra embryon c splanchnopleunc (v isceral) and somatopleuric (parietal}

mesoderm only cover or line the foetal membranes and play no part in the formation of the embryo The mesoderm covering the amnion for theoretical reasons u regarded as somatopleuric (Chapter \ I)



At the stage of development now reached (about the 1 2 th day) the embryo itself is represented by two apposed discs of cells — embryonic ectoderm and embryonic endoderm. The embryonic ectoderm forms the “floor” of the amniotic cavity and is continuous at its edges with the amniotic cells. These ectodermal cells as yet show no regional differentiation. The embryonic endoderm, on the other hand, forms the “roof” of the primary yolk sac It shows the localized thickening already referred to as the prochordal plate. There is as yet no evidence, in the embryonic disc, of the presence of a third germ layer (mtra-embryonic mesoderm) The next iinportant phase in development is a regional difiei entiation of the embryonic ectoderm to forma primitive streak and the derivation from it of this mtra-embryonic, or secondary, mesoderm


The primitive streak is an area of the


to form a bilaminar membrane thcV/oarai mtnbtane (Figs 43 44 and 47) The primitive streak persists as m actuely proliferating area until about the ('i e , the end of the

somite) stage It then undergoes retrogressive changes and rapidly diminishes in size


As the intra embryonic mesodcrtti is extending forwards there is, at the anterior eKtrerrulv of the primitive streak a farther proliferation of the ectoderm known as Hensen s node or the /)rtmUiie i-not In the centre of this proliferation an invagination of the ectoderm (the blaslopore) occurs (Figs 43 44 Aiiti 4b) Thtc&M> sc D

of the invagination probabl> represents the blastocoelc (see Chapter XVI) of lower forms while its margins are comparable to the dorsal portion of the blastopore of such forms The pnmitn e streak itself is believed to be homologous to the lateral and ventral lips of the blastopore (See Chapter XVI for the phylotjcnetic significance of the blasto pore and Chapter VIll for its signi ficance m developmental mechanics )

In the mid line of the embryonic disc a cord of cells is budded forward from Hensen s node between the ecto derm and endoderm, this cord u known Mthtnotochordal otkead ^ro«Jf{Fig 43)

The anterior extremitv of the process comes into contact with the postenor edge of the thickened prochordal plate by this relationship the anterior end of the process becomes relatnel> fixed The invagination of the blastopore then extends into the notochordal process to form a cavity, i)M\/notochoTdal or archenUTtCi canal (Figs 43 and 44) As the anterior end of the notochordal process is relatively fixed further growth m length of this process is mainly brought about by the prolifcra uon of cells at Hensen s node which with the primitive streak migrate* or IS earned, m a caudal direction as the notochordal process and embryo increase in length

— ce eot u

Fio 40 — A transverse section through the anterior p$n of the embijonie disc and related partof ihechononic vesicle

or the tdwjrds Jones Brewer embr^ ' '

A Riesoderma] <.ondensat(On i B Vdsculooenic space x c 200

r cmbr>o (after Bre\ er)

"" — "i connecting stalk

Meso*™ „ budded off from the sides of Hensen s node (Fig 49D) connnuous svilh that tvhtth ts domed from the rest of the pnntth.e streal The notochordal proeess now fuses with and becomeMWereatotd the eraboon.0 endodetm ( 44 and 40B) r-Opemnirs appear m the floor of the notochordal canal tvhtch consequently commumcale yvith the toS

and Im’ Tb ■*"“ n o f '■rought tmo tommumcanon ( 44 46

and 48) The open, ngs m he floor of the notochordal canal become confluent and a «ooy e .s foraied on the under surface of the notochonjal process Thts groove becomes sha 1 [ot,er



plate (Fig 49A) and as development proceeds it extends in a caudal direction, differentiating out of the notochordal process as this process elongates in association with the proliferation and backward migration of Hensen’s node. Thus the notochordal tissue, from the prochordal plate to the opening of the notochordal canal, instead of lying between the ectoderm and endoderm becomes temporarily intercalated in the endoderm so that it forms an axial stnp separating the embryonic endodeim in the roof of the yolk sac into right and left portions as far back as the notochordal canal As the embryo elongates the definitive notochord is









, A ><

Fig 41 A transveise section through the posterior part of the same embryo as Fig 39, showing the primitive streak and early development of the intra-embryonic mesoderm

mesodeimal X c. 200

condensation in connecting stalk

developed from the notochordal plate by a longitudinal folding of the latter and Its separation from the endoderm This folding process commences cranially and progresses caudally as the embryo grows (Fig. 49). The endoderm, ivhich probably includes some remaining intercalated notochordal plate cells, then becomes continuous once more across the mid-hne as the definitive notochord separates from it (Fig. 50).

In an embryo at the time when the notochord is separating from the notochordal plate, three phases of notochordal formation can still be recognized (a) the proliferation of cells at Hensen’s node; {b) the intercalation of the cells into the roof of the yolk sac to form the notochordal plate; and (r) m the anterioi part, the separation of the cells from this plate to form the notochord There is thus an antei o-posterior gradient involved in the process.

By the fourth week, when the embryo is approximately 4 mm long, almost the entire length of the notochord IS in Its final position between the endoderm in the roof of the yolk sac and the ventral aspect of the neural groove, or tube, which has now formed from the overlying ectoderm. In the tail region, however, the same relations are


present as existed at Hensen’s node soon after the notochordal process appeared. The blastopore, which is now m the floor of the neural groove, persists as the dorsal opening of the r^otochordal (no^v called neurentenc) canal. The anterior extremity of the notochord remains attached to the endoderm for a long time (Figs 163 and 375) The further history of the notochord will be discussed in connexion wuth the development of the skull and vertebral column (Chapter XIII). ^


The intra-embryonic mesoderm arises, for the most part, by proliferation from the in that part of the embryonic disc known as the primitive streak (page 48). The priim



streak, ho\\c\er is not sold) concerned uith the formation of mesoderm for Heuser and Streeter (1941) have shown, tn the monke>, that the cells of this area of the enibr>onic disc arc primitive and plunpoUnttal and arc, therefore capable of givini, rise to further ectoderm or to endoderm Moreover, some

intra embryonic mesoderm as will q

be described more fuliv later arises

from ectoderm otlicr than that of the H^V

primitive streak (page 270) The \c^ *

mtra embryonic mesodermal cells

arising from the primitive streak pass -s/® 'X-A

laterally betvs een the ectoderm and

endoderm until they come into con 0 /)

,act ,u.h .he pr,mar> extra embr, <j]

onic mesoderm covenrlg the amnion \v

and yolk sac (Fig 49) The meso ^ I \o f c o u e

dermal cells also migrate forward I 1 / 9b“ « ^

into that part of the embryonic disc /fi/

which lies anterior to Hensen s node /iJ

and flank the notochordal process V\\

which has arisen from it A small ’ , , *^v \

amount of mesoderm mav also anse

from the sides of the notochordal %*

process (Hill and riorian 1931 and

others) \s the growth in lenctil of \ »chrmai.c ihrep dimmi t nsl reconstnjction

.1.- .,K 1 ,j»i ,.c, ^ of llie I dwaroj Jon« lires rr oiiim \ cut lUrface of primi

the notochordal process is accom tor streak It future ronnecunc stalk C margin of the

panied by a progressive caudal dis endoderm ofthermhryonre due a c aoo

placement ofthe primitiv c

streak the mesoderm pro

duced by the latter comes ^

to lie on each Side of the V^X /esv \ c

notochordal process This ^ ^

ectoderm and endoderm s — J P ^

of the disc except in the ^

mid line from Hensen s " '* **.. * *’

node to the anterior oT«e o e v r/

tip of the notochordal \ — _ ' ‘

process in the region of k—— ToftTrK^-^ iFc, , U

the prochordal plate and « 

(in the later presomite /

embryos) in the region of ^ ^ \^|5

the cloacal membrane

With the formation

of the neural groove and |]'

the separation of the /" < u - fl*

definitive notochord from ^

the notochordal plate the p.e « -\^t.onrf rchemanc three d, men,. onal recoatiracon ofthe Hugo intra embrvonic mfsO embno ThrcoloursrhAmmn >hi> «;».<» rend ... i?.-. ..._j

intra embryonic mesO derm on either side of the notochord becomes

emboo The Mlour schemes m this figure and m Figs 44 and 47 are similar The nuclei of the «idodertn are shown in -yeUiyw of the notochordal process

m red ol the ectoderm and extra embryonic mesoderm in black andofihc mesoderm arising from the primiuve streak in blue X c qo



thickened to form a longitudinal mass known as the paraxial mesoderm This paraxial mass when traced laterally gradually thins into the lateral plate mesoderm It is this lateral plate mesoderm which becomes directly continuous with the extra-embryonic mesoderm beyond the margins of the disc

By the 21st day of development the paraxial mesoderm on each side of the notochordal process and, later, of the definitive notochord, becomes segmented into paired cubical masses called somites (Figs 50, 97 and g8). The first somite is formed a short distance behind the cephalic tip of the notochord and successive somites are progressively formed by differentiation from the paraxial mesoderm as it arises from the primitive streak. The first pair of somites to be formed in man and higher vertebrates are the first occipital; and each subsequent pair of somites lies immediately behind the previously formed pair No somites are formed in the mesoderm in front of the notochord. The paraxial mesoderm, however, extends forwards as far as the anterior end of the future brain plate as a diffuse mesenchyme The somites are

Fig 44 — A sectioned schematic reconstruction of the Rossenbeck embryo (Hochstetter, Pehl) Colour scheme similar to that in Fig 43 The notochordal canal now has several communications with the yolk sac The allanto-enteric diverticulum has grown into the connecting stalk where it is surrounded by mesoderm (A) derived from the primitive streak B — communication between notochordal canal and yolk sac C — cardiogenic area X c 50

somewhat triangular, on transverse section, with medial, ventral and postero-lateral walls (Figs. 50, 230 and 274) Each consists at first of epithelioid cells enclosing a somite cavity, the myocoele The myocoele later becomes occluded by the proliferation of the cells of its walls (Chapter XIV) Altogether 42-44 pairs of somites are formed in the human ytnbryo The lateral plate which, for the most part, remains unsegmented in man and higher vertebrates IS attached to the ventro-lateral angle of each of the somites by a continuous tract o mesoderm called the intermediate mesoderm (Fig 230) This intermediate mesoderm later undergoes changes which result in the formation of the excretory system and the gonads In front of the somite region the lateral plate mesoderm of each side extends forwards within the margins of the embry^omc disc and eventually fuses in the middle line in front of the prochorda plate which, with the overlying ectoderm, forms the bucco-pharyngeal membrane This latera plate mesoderm, of bilateral origin, m front of the prochordal plate is called the cardiogenic mesoderm as the heart later develops in this region.



Small isolated cas toes nosi appear on each side .n the hlerd mesoderm and soon hecorne .onfluent to form a single casit> the intra embrjonic coelom Tlie casitations extend fonsar on each side n .tlnn the embrvo until thex fuse aerosj the middle line in the cardiogenic mesoderm therebj forrains a single horseshoe shaped intia embryonic coelom

Tic. 45 — \ dra in^ of the dorsal aspret of a modfl of an i8da> prcsomite eml rso The letters \ B C D and r indicate the let els of the sections A BCD and F of Fig 49 x c Sj (After Heuser 193'’

FiQ 46 — \ drawing t f the \entnl aspect of the presomiie emlr>o illustrated in Iig 43 y c 53 (\fier Heuser )


Thts coelom is at first a closed space later hotsever, at the litcril edt'C of each of its caudal extremities itformsacommunicitionwilhthecxtra embryonic coelom (Fiqs 50 and 119) The cavity is lined by the intra embryonic parietal, or somatopleuric mesoderm m contact with the ectoderm and the mtra embrvonte visceral or splanchnopleunc mesoderm m contact with the endoderm The anterior portion of the intra embryonic coelom which passes trans versely across the middle line of the front part of the embryonic disc anterior to the bucco pharyngeal membrane is the pnmordium of the pericardium and has the cardiogenic plate (of



splanchnopleunc mesoderm) m its floor (page 137). With the formation of the head fold and the resulting reversal of the head end of the embryo the pericardial portion of the intra-embryonic coelom is carried ventrally and caudally, and is also reversed so that the endothelial heart tubes arising from the cardiogenic plate now invaginate its splanchnopleunc roof (Figs, 83, 120 and 162), As a further result of growth changes m the anterior region of the disc the mesoderm (fused splanchnopleunc and somatopleuric) which initially was anterior

Fig 47 — A schematic representation of the germinal layers of the Heuser presomite embryo from the dorsal aspect Colour scheme as in Fig 43 In the upper half of the illustration (right side of the embryo) the ectoderm has been removed to show the extent of the mesoderm A window has also been made in the latter to show the underlying endoderm In two situations (prochordal plate and cloacal membrane regions) the ectoderm and endoderm are in contact X c 67



to the pencardium nou lies caudal to it and below the de\ eloping foregut This mass ol mesoderm is called the septum transiiTSum

Each dorso lateral angle of the pencardial ca\’it> is still continuous with the corresponding, caudalh directed limb of the intra embryonic coelom which passes dorsal to the septum transtersum on the side of the foregut As these limbs are communications between the pericardial ca\it> and that part of the intra embryonic coelom which will become thepentoneal

5 ^


cavitv they are called the pmcardio-perUomal canals (Fig. 217). With the growth m length S the’foregut these canals become progressively longer and, soon each is invaginated from the medial aspect by the developing long bnd of the side concerned. The pericardio-pentoneal Sials can now be called the plmral cavtUes. Thus at this stage the whole intra-embn'onic “dom consists of a median pericardial cavity, two primitive pleural cavities and the peritonea cav ty The pericardial cavity communicates on each side with the corresponding pleural Sv!ty by way of a pericardio-pleural opening. Each pnmitive pleural cavity is m communiLtion by way of a pleuro-pentoneal opemng with the peritoneal cavity, the latter is Tfree commLcation. on each side of the yolk sac, with the extra-embryomc coelom.

In later development the pericardio-pleural and pleuro-pentoneal canals are obliterated and the pericardium and the two pleural cavities are completely separated from the peritoneal cavity (pages 218 and 220). Still later in development the peritoneal cavity itself becomes


1930) X c 140

completely closed off from the extra-embryonic coelom at the umbilicus rsomato lesult from the subdivision of the original intra-embryonic coelom possess

pleuric) and a visceral (splanchnopleuric) wall The latter always forms cubdivision

organ which appears to he within any of the cavities The further deve opmen

of the coelom is described in Chapter X.


The prochordal plate is a circumscribed area of thickened embryonic en ° j jj,g

anterior part of the roof of the yolk sac This endoderm is in contac wi ^ ^

anterior part o: me rooi oi me yoiK sac xius vi,nrpss and

ectoderm, no mesodeim being interposed. The anterior tip of the Whei

ecioacnu, uu nicsuucini uemg, m-Li-i jjuavu. --x- nlfii-p When the

later the notochord itself, comes into contact with the posterior edge o e p • lateral plate mesoderm of each side grows forwards into the cardiogenic par o disc It skirts the periphery of the prochordal plate The prochorda p ate le gnt

same plane as the embryonic disc, but with the formation of the hea , pardiogemc of the anterior portion of the neural plate, and the caudal displacemen ° , .p 3^),

mesoderm, it comes to he in a plane at right-angles to the anterior end o e overlying

The prochordal plate now forms the anterior limit of the foregut and, toge er -membrane

ectoderm, with which it remains in direct contact, constitutes the buccop arynge



This membrane soon comes to be bounded on each side bj the deseloptng branchial mesoderm (see later) tihich bulges anteriorly so that the membrane lies m the floor of an ectodermal depression— the stomatodaeura, or pnmitne mouth In late somite embryos (Iig tot) the membrane breaks dow-n thereb> establishing contmuil) between stomatodaeum and foregut

In lower \ertebrates the cells of the endodermal prochordal phte are known to give ongin losoraeoftheintra embryonic mesoderm m the central region of the head These cells may also possess an organizing effect on the adjacent neural tissue The fate of the prochordal plate m

O C !>««' E


Fig 51 — \ draw n® of a trans>prscseciion through a 16 somite human embrvo at the level of the lit pharyngeal arch buccopharyngeal membrane and otic placode (after Bartel mezandLvans 19 C) X c 133 A — tangential cut through cranial lip of embryo

mammals can only be surmised from its history in these more primititely organized \eitebrates but there is good reason for considenng it to be an important developmental apparatus m all vertebrates


In early primitive streak stages there is an area at the posterior end of the embrvomc disc where the ectoderm and the endoderm remain m contact no intra embryonic mesoderm being interposed This is the primitiv e cloacal membrane The area of contact is at first characterized bv a thickening of the endodermal cells in this region the cells soon become flattened and together with the ovtrlyang ectoderm form the doacal membrane In the later presomite stages this membrane increases m size and extends backvtards on to the dorsal surface of the proximal



part of the allanto-enteric diverticulum (Fig. 44). The mesodermal cells arising from the posterior part of the primitive streak pass backwards around the sides of the cloacal membrane to augment the mesoderm of the connecting stalk, but do not interpose themselves between the layers of the membrane itself,

At the time of its first appearance the cloacal membrane is situated posterior to the primitive streak and its ectodermal surface is directed dorsally. With the development of the tail fold and reversal of the posterior part of the embryo m the late presomite and early somite stages the cloacal membrane gradually comes to be situated on the ventral surface of the embryo (F igs 79, 83 and 144). With further growth of the tail the ectodermal surface of the membrane comes to be directed towards the developing infra-umkbcal region of the anterior abdominal wall (Figs 144 and 233). The original posterior margin of the membrane is now continuous with the caudal attachment of the umbilical cord. In later stages the development of the ge, ital tubercle and infra-umbihcal part of the anterior abdominal wall and the decrease in s )f ihe tail and post-anal gut cause the cloacal membrane to undergo a rotation m the reverse ( on so that it is directed posteriorly and downwards. With the development of the u)ou i ptum the cloacal membrane becomes subdivided into an anterior part, the urogenital i/iemium and i posterior part, the anal membrane (page 212). Later, as is described in fJli ip ei ^1, ihese membranes break down to give continuity between the cloacal derivatives and ill'" xieior

Tiip luiihc, history of the embryonic disc must now be delayed while the implantationi 01 r lie hi ."■toc' 't and the development of the foetal membranes are considered. The description ol the itf \elopment of the embryo itself is resumed in Chapter VII.


\llen, r r.wi I P , Newell, Q, U , and Bland, L J. (1930) Human tubal ova, related corpora lutea and

ut I' lubui! Contrib Embryol , Carnegie Inst. Wash, 22 , 45-76

Blandae 1 i me’ Money, W L (1944) Observations on the rate of transport of spermatozoa in the female

!tei . 1 u let of the rat Anat Rec , 90 , 255-260

Bo\d, J I' Hirnilton, W J,, and Hammond, J , Jr (1944). Transutenne (“internal”) migration of the o\u m sheep and othei mammals J Anal, Land, 78 , 5-14.

Biewer, J I ( <9381 A human embryo in the bilaminar blastodisc stage (the Edwards-Jones-Brewer o\um) Contrih Embryol, Cmnegie Inst Wash, 27 , 85-93.

Cary, W H (1936) Duration of sperm cell migration and uterine secretions J Am Med Assoc, 106 , 2221-2223

Chang, M C {igsD Fertilizing capacity of spermatozoa deposited into the fallopian tubes Nature, 168 , 697-698

— and Pineiw, G ^951) Physiology of fertilization in mammals Phys /?w , 31 , 1-26 Corner, G \\ • 1932! Cytology of the ovum, ovary and fallopian tube Special Cytology (ed Cowdry),

2nd ed , pp 1567-1607 Hoeber, New York

Florei, H , and Walton. A (1932) Uterine fistula used to determine the mechanism of ascent of the spermatozoon in the female genital tract J Physiol , 74 , 5-6 {Proc Physiol Soc )

Florian, J (1933) The early development of man, with special reference to the development of the mesoderm n membrane J Anat, Land, 67 , 263-276 a h ,1

Gerard, P (1932) Etudes sui I’ovogenese et I’ontogenese chez les Lemuriens du genre Galago Arch ae Biol , 43 , 93-152

Hamilton, W J (1934) The early stages in the development of the ferret, fertilization to the formation of the prochorckl plate^ Trans Roy Soc, Edin , 58 , 251-278

U 944 ) Phases of maturation and fertilization in human ova J Anat, Land, 78 , 1-4 (1949) Early stages of human development Ann RCS Eng, 4 , 281-294 Hamrnond, J. (1925) Reproduction in the rabbit Oliver & Bovd, London

~ (1941) Fertility in mammals and birds Biol Reviews, 16 , 165-190 , p ,

Hartm^, C G {1933) On the survival of spermatozoa in the female genital tract of the bat Qjiart ne 5101,8,185-193 F 6

and Ball, J (1930) On the almost instantaneous transport of spermatozoa through the cenix an uterm of the rat Proc Soc Exp Biol and Med , 28 , 3 12-3 14 Hertig, A 1. (1935) Angiogenesis in the early human chorion and in the primary placenta of the macaq nmnkey Contrib Embryol , Carnegie Inst Wash , 25 , 37-82 i pn

° I ^*941) Two human ova of the pre-villous stage having an ovulation age of about eiev ^ J '"t respectively Contrib Embryol, Carnegie Inst Wash, 29 , 127-156 and Rock, J (1945) Two human ova of the pre-villous stage, having a developmental age of abputse respectwely Contrib. Embryol, Carnegie Inst Wash, 31 , 65-84 and Rock, J. (1950) Personal communication

CHAPTER V Missing?


In the late presomite stages the embr>o consists of an outer ectodermal and an inner endo dermal la^er of cells separated b> an intermediate later composed of the mesoderm and nolo chord (Fig 49) In normal detelopment the cells of these three primary germ layers make specific contributions to the formation of the diflcrcnt tissues and organs Experimental embryology has demonstrated that the specificity of these contributions is not so rigid as ttas formerly believed (Chapter VIII) nevertheless it is important to know what each of these layers normally contributes to the different tissues and organs of the older embryo


The embryonic ectoderm is an epithelial layer which is continuous laterally with the flattened amniotic ectoderm From it m normal development there arise —

1 The epithelium of theskm (thccpidermis) anditsdcnvatives — hair nails the epithelial cells of the sweat and sebaceous glands and of the mammary glands

2 The epithelium of the mucous membrane and glands of the lips, cheeks gums pari of the floor of the mouth and of the palate and that of the nasal cavities and paranasal sinuses

3 The epithelium of the lower part of the anal canal and of the terminal parts of the genital and urinary tracts

4 The primary dental laminae which give rise to the enamel organs of the teeth

5 Rathke s pouch which becomes the anterior (buccal) part of the hypophysis cerebri

6 The lens of the eye the anterior epithelial layer of the cornea and the outer layer of the Xvmpanic membrane

7 The central nervous system including the retina the two epithelial layers of the ciliary process and ins and the optic nerve but excluding the blood vessels and probably, the microglia

8 The peripheral nervous system including the sympathetic nerve cells and fibres the medulla of the suprarenal gland and the neurolemmal sheath cells

9 The sensory cpithelia of the olfactory and auditory organs

10 The musculature of the iris and possibly certain other structures which are usually considered to be of mesodermal ongm c g branchial cartilage meninges and dermal pigment cells (the latter structures are sometimes said to be mes ectodermal in origin for discussion see pages 271 and 366)

In the early stages all the ectodenoal derivatives are cpithelia and they remain essentially epithelial tissues throughout life except m the nervous system where the cells become highly specialized and in the mes ectoderm ® ’






Fig. 94 A scheme to show the differentiation of various cell typei'from the undifferentiated mesenchymal cell



transformed into other types e g , fibrocytes in certain circumstances, may acquire osteogenic properties and it is even possible for chondrocytes to become osteocytcs

In some varieties of developing connective tissue the mesenchymal cells take on a fat storing function (Fig 94) The fat is initially stored as small discrete droplets which later increase in size and coalesce so that the cytoplasm of the cell becomes a peripheral nm round the fat Some mesenchyme cells, which appear to be mes ectodermal (Chapter XV) acquire the property of synthetizing melanin, to form melanoblasts (dendritic cells) Other mesenchymal cells show a special affinity For particulate matter and for certain colloidal dyes These are the macrophages which are usually classified as fixed {histuu^les) or wandering {monocytes) In certain regions, e g , luer, spleen, lymphatic system and bone marrow, the macrophages are associated with reticular fibres and arc then classified at belonging to the reticulo endoiheltal yslem Other mesenchymal cells in close proximity to blood vessels, develop granules which stain metachromitically They are called mast celts and they resemble the basophilic Icucocv tes of the blood although they do not appear to be genetically related to them (Fig 94) Other cells of mesenchymal origin are the so called plasma cells and the fixed eosinophils


A most important and highly specialized group of the mesenchymal cells is that which gives origin to the blood and the vascular and lymphatic systems Some of these cells remain fixed but become thinned out and so arranged that they enclose a fluid matrix m which another important strain of mesenchymal cell is found The former are the endothelial cells of the blood or lymph vessels (Chapter IX) the latter are the free cellular elements of the blood and lymph the plasma of which is the fluid matrix

The first blood cells and blood vessels arise in the extra embryonic mesoderm in early primitive streak stages Blood vessels arise at about the same time m the splanchnopleunc mesoderm of the yolk sac in the somatopleuric mesoderm of the chonon and in the mesoderm of the connecting stalk (Chapter V) The blood cells however, are restricted in their extra' embryonic development to the wall of the yolk sac and allantoic diverticulum The earliest stages in the development of human blood are unknown but from comparative embryology and from the study of the less advanced areas of blood formation in the yolk sac of presomite human embryos of about eighteen days it seems likely that the first blood cells arise from mesenchymal cells lying between the yolk sac endoderm and the splanchnopleunc mesothchum \\hcthcr these cells are derived from mesoderm or from mesenchyme of endodermal origin* is not finally established, but there is no doubt that they should be regarded as mesenchymal

Haemocytoblasts The first recognizable blood cell is the haemocytoblasl (Fig 94) which IS a sphcncal or slightly polygonal cell with basophilic cytoplasm It resembles closely the large free basophil stem cells (myeloblasts and large lymphocytes) found in all embryonic and adult haematopoietic foci Its nucleus is large with acidophilic nucleoli (Fig 95) Accord ing to one interpretation (the monophylctic theory ) the haemocytoblasl is the stem cell which gives origin to all the cellular elements of the blood The haemocytoblasts proliferate by mitosis so that small groups of them are formed, among which some acquire haemoglobin (pnmitiveerythroblasts) These groups are the so called ‘blood islands (Fig 95), and initially they appear to possess no endothelial covenng Soon however the mesenchymil cells surrounding the blood islands become flattened to form the specialized endothelium

Erytbroblasts and Erythrocytes The haemocytoblasts m the yolk sac wall give origin to a generation of primitive erythroblasts which become transformed into primitiie eiyihrocytes and subsequently to an apparently independent lineage dtjimtxu erythroblasts and erythrocytes The primitive erythroblasts constitute the most numerous group of cells m the

volk WTOdcclb arc initaally formed from the endoderm cells of the secondary

the mole)^ Barlelmez 1940 Gladstone and Hamilton 1941 Mossman unpublished observations m



blood islands of the early yolk sac. Initially they are similar to the haemocytoblasts, but they gradually become acidophilic as haemoglobin accumulates in their cytoplasm (Figs. 95 and 96) The early primitive erythroblasts are capable of multiplying by mitosis, but with increasing maturity the nucleus becomes pyknotic and eventually may be extruded or disappear. The resulting non-nucleated acidophilic cell, which at first shows a reticulated remains of the nucleus, is a primitive erythrocyte. After the 35 mm. stage the primitive erythroblasts cease to show mitotic division and they, together with their derivatives, soon disappear.









m t


early prim





ter- '>

  • c*




( A,-'

transitional haemocytoblast j

1' '/rrk-r .




■' S* A?;






» y t N

I,,-**, »

/ >•

, V

w- Ysy (A- p - Y

, ' * .A-f-a'- ' ' HAEMOCYTOBLAST

- Y Fig 95. — drawing of part of the wall of the yolk sac in the abenabryonic region (of the Shaw embryo) showing the different types of blood cell lying within and in the neighbourhood of a vascular space which IS lined Tvith endothelium. (Modified from Gladstone and Hamilton, 1941 ) X c. 750. (Reproduced by courtesy of the Journal of Anatomy.)



The definitive erythroblasts, which are distinctly smaller than the primitive erythroblasts, begin to appear at about the 10 mm stage (Gilmour, 1941) and gradually increase in number until, by the 30 mm stage, they and the cells derived from them, exceed the number of primitive erythrolilasts and erythrocytes in the foetal blood. The definitive erythroblasts also arise from the haemocytoblasts and they are first found in the wall of the yolk sac. Soon after their fimt appearance, however, they are found multiplymg in the mesodermal stroma of the hver (page 20 ) and, rather later, in the developing spleen (page 224) and, occasionally, in other mesoderma




foci e g thp vitsonephros Later still hacmatopoieuc activity commences m the developing bone maTToiL (clavicle, 43 mm , humerus, 57 mm femur, 75 mm see Gilraour, 1941) By the end of the third month the bone marrow has become the mayor site for cry throcytopoiesis, although the liver and spleen normallv continue to form new red blood cells until just after birth

The definitive ervthroblasts go through Stages of development comparable with those of the primitive crythroblasts They tend however to retain their basophilic properties for a longer period and the cells resulting from their differentiation— the definitive ervthrocvtes— are smaller and more circular than the primitive erythrocytes In the transition from the definitive erythroblast to the defimtive erythrocyte the nuclei of the cells also show the reticulate appearance ( reticulocytes )

The time of appearance of haemoglobin stamable by cosin in the crythroblasts varies and in general two varieties of erythrocyte formation arc recognized In one variety (megaloblastic eryihropoiesis) haemoglobin appears early in large crythroblasts with large nuclei which preserve their nuclear structure The erythrocyte which develops from such erythro blasts IS called a megalocytc and is larger thvn that (normocyte) found m normal adult blood In the other variety (normoblastic ery'lhropoiesis) haemoglobin appears late m small erythro blasts with pyVnotic nuclei and the resulting cell, a normocyte is vnthm the normal size for adult blood All primitive crythroblasts and the definitive crythroblasts of early foetal life giv e rise both to megalocy tes and normocy ics After the first few w ceks of post natal life normal cry thropoiesis is entirely normoblastic

Foetal Haemoglobin There is much evidence to show that the haemoglobin m foetal blood is not identical with that found post natal)} This statement holds for human blood as well as for that of many other mammals In some of the latter there is evidence to show that the oxygen dissociation curve of foetal haemoglobin differs from that of the mother jn a manner which facilitates the passage of oxygen to the foetus In the human however, foetal haemoglobin does not show this teleological character (For further discussion see Kendrew, » 949 )

Leucocytes, Lymphocytes, Monocytes and Megakaryocytes The haemocytoblasts are also capable of giving origin to granular leucocytes, megakaryocytes, monocles and lymphocytes (Fig 94) In the yolk sac wall of early embryos m addition to the haemo cytoblasts and crythroblasts some megakaryocytes, a few phagocytic cells and possibly, primitive mvclocvtes arc present

LftfoJg/ojtoiexa Within the embryo ufiret found at about the tBmm stage in the mesenchyme of the liver and various connective tissues The cells promyelocytes anse from haemocyto blasts which appear to differentiate in stiu from rounded mesenchymal cells These promyelo cytes can become neutrophilic eosmophibc or basophihe The promvelocytes give ongm by multi plication to myelocytes which become transformed into polymorphonuclear leucoeyts (Fig 94) By the 43 mm stage leucocytopoiesis has commenced m the bone marrow where the promyelocytes undergo changes comparable to those just described Mvelocy’tes and leucocytes first appear in the blood stream at about the 50 mro stage (Gilmour, t94i)

The stem cell in lymphocytopousu is the lymphoblast which apparently, may anse either directly from a mesenchymal cell or from a baemocytoblast Lymphoblasts first appear jn the connective tissue around ly-mph vessels (page 169) at about the 30 mm stage They begin to appear m the lymph glands at about the 50 mm stage by which time the lymphatic vessels contain some Ivmphocytes They are also found dunng embryonic life in the thymus gland and spleen and for a short time in the liver and bone marrow but not in the wall of the yolk sac The lymphoblasts can become transformed either into small or large lymphocytes As h-mphocytes are first found m the blood of 26 mm embrvos they probably also arise directly from haemoev tobUsts in the circuhtmg blood since at this stage there is little lymphocy topoiesis in the connective tissue The haemoev toblasts can also give ongm to monocytes and mega warvocytes and the latter mav abo anse dircctlv from the mcsenchvmal cells (Fig 94)




Ehrlich, the initiator of modern haematology, considered that the erythroblasts and myeloblasts had an origin different from that of the lymphoblasts This is the so-called dualistic interpretation of the origin of the blood cells and is one of the modifications of the polvphyletic theory which postulates that there are two (or more) varieties of stem cells from which the different hinds of blood corpuscles are derived. Most modern haematologists support the monophyletic theory of Maximow, according to which there is only one haematogenous stem cell — the primitive blood cell or haemocytoblast of Pappenheim There is still, however, a lack of general agreement on the precise relationship of the different varieties of blood cells to each other Most investigators believe that in the early stages of development there is only one haemocytopoietic tissue which gives origin, m several different situations, to myeloid (erythrocytes and granular leucocytes which originate, m post-natal life, from bone marrow) and lymphoid (lymphocytes and probably monocytes which originate, post-natally, in the lymph nodes and splenic tissue) elements It is only later in embryomc life that the lymphoid and myeloid tissues become separated. The original sites of blood cell formation are only temporary and in later development haematopoiesis is taken over by those organs which will form the new blood cells m the adult.


« ) I

l' ( ^


'/' '-X



.1 ’^7


/ A ■>' 'ft'

! . — I'

• A,

\ X l.V' . .

X- ' \ 1. ft








Fig g6 — A drawing of part of the wall of the yolk sac near its attachment to the embryonic disc A well formed blood island is seen on the right of the drawing (Modified from Gladstone and Hamilton, 1941 ) X c 750 (Reproduced by the courtesy of the Journal of Anatomy )

There is also controversy as to whether or not the intra-embryonic haematogenous foci arise in situ from intra-embryonic mesenchyme (theory of “local origin”) or arise from haemocytoblasts (of yolk sac mesodermal origin) which have migrated into the embryo where they settle dowm to form areas of prohfei ation (theory of “extra-embryonic origin of blood cells J. Most of the evidence supports the view that the intra-embryonic mesodermal cells have the same potency to differentiate into blood cells (or blood vessels, page 136) as the cells of the yolk sac wall How'ever, Irwin (1949), in studying the genetics of antigens intrinsic m the red bloo cells of cattle, has shown that in the case of non-identical twins each calf is born with, an retains throughout life, all the inherited intrinsic erythrocyte antigens of its twin as well as those inherited from its own sire, where the sires can be proven by other characters to be differentSince these antigens are only found within red blood cells, it follows that the primordial ce s from which the red blood cells are derived must have migrated and become established mutua > m each foetus This natural transplantation of embryonic tissue is made possible by t e well-known anastomatic union of the choriomc vessels in fraternal bovine twins

The problem of blood development is yet further complicated by lack of agreement on ti relationship of the differentiating blood cells to the endothelium. Some workers believe t a


the er> ihrocy ics arise intra \ ascularlj and the granulocytes extra v ascularly The earliest y oik sac hacmocytoblasts appear before the endothelium has difTcrcntiated Most of the hacmato poiesis inside the body of the embryo is extra \ascular, the cells secondarily migrating into the blood vessels where they undergo further differentiation In the earlier stages however, erythrocytopoM-sis appears to be largely mlta vascular but later m the liver and marrovv IS mainly extra vascular (Gilmour, 1941)

All modern investigations of the embryonic blood demonstrate that the problem of the development of its cells is onlv part of the wider problem of the developmental potencies of the primitive mesenchymal cell and that it is also closely related to the development of the rcticulo endothelial system (for details of these problems sec Downey 1938 and Bessis 1948)


Bartelmez G \\ and Fvani H (igsC) Devtlopmcnt of the human embrvo during the p<ncd of somite formation inctuding embryos VMtii 2 to >C pain of somiirs Cent ib Emb’yel Ca negit Insl tliuA 17 1-G7 Besiis M (igtB) Cytologic Sanguine Masson Pam

Bloom \\ (1937) Cellular differentiation and tissue culture Phtiiol Her 17 589-C17

and Barielmez C \\ (lOl®) Haetnainpoiesis in young human embryos Am J -inat 67 "1-54

Downey H (1938) Handbook of Haematology Hoeber Nesv ^ork Fischer \ (>946) Biology of Tissue Cells Cambridge Unis Press London

Gilmour J R (1941) Normal haemopoiesis in intrauterine and neonatal life J Path and Bad 52 25-55 Gladstone R J and Hamilton \\ J (igp) \ presomite human embryo (Shan) with pnmitise streak and chorda canal with special reference to the deselopment of thesascular svstem j inal land 76 (>-44 Gfuenwald P (194a) Common traits in development and structure of ihc organs originating from the ceielomic s all 3 Moffh 70 313-387 Hertwig O (i83i) Die Colomtheone Jena

Irwin M R (1949) Immunological studies in embryologs and geneiica Quad He Bid 24 109-123 Kendrew J C (1949) Foetal Haemoglobin FnJeatou 8 Co-fi>

Maximow \ {1927) Bmdegewebe und blutbildende Ces ebe 7>i llandb d rnikr \nat de Mensclien fv MolIendorfT) 2 Ft I Springer Berlin

Willmer E N (1945) Gros th and I ormm Tissue Cultures /« Fssays on Cro' ih and Form edited bv Clark and Medw ar Clarendon Oxford




The human embryo grows from a single cell of about 140/i m diameter and weighing only a minute fraction of a milligramme to a full term foetus with a total length of over 50 cm , a weight of over 3000 grams and corhposed of many millions of cells of different types This growth, which may be defined as increase in spatial dimensions and m weight, is the resultant of three different processes (Needham, 1942) {a) Multiphcative, increase in the number of cells, {b) Auxetic, increase in the size of the cells, and {c) Accretionary, increase in the amount of nonliving, intercellular material. The rate of growth, i.e , the percentage increase in weight and spatial dimensions per unit of time, is most rapid in the earlier stages and decreases as pregnancy advances although, of course, the absolute increment, per umt of time, increases (regularly) during this period. To reach a weight of 3000 grams the embryo requires about 266 days. The length of human pregnancy is usually taken as being 10 lunar months, 280 days (with a range, however, of 250-310 days), from the time of the onset of the last menstrual period. As has been described in Chapter III, however, ovulation normally occurs at about the 14th day of the menstrual cycle and so the ovulation age of an embryo is normally about fourteen days less than the “menstrual age.” “Coital age,” owing to the short duration of fertilizable life of the ovum and of fertilizing capacity of the sperm, can be taken to be within two or three days of the ovulational age and the “fertilization age,” which cannot, of course, be determined absolutely in the human subject, may be anything up to four days less than the “coital age ” In obstetric practice “menstrual age” is almost invariably used, but with increasing material of well established coital age available and with increasing certainty in the time of ovulation being at about the middle of a 28-day menstrual cycle, it is now possible to estimate the ovulational age of human embryos much more accurately than was hitherto possible.

As it grows from the spherical fertilized ovum to the full-time foetus the embryo undergoes many changes in its form. These changes are an expression of differentiation within the embryo and are due to differences in rates of growth of different parts of the embryonic mass in various directions. The growth of the whole organism is merely the sum of the growths of all its parts while the individual parts increase, or decrease, in relative size (both to the whole organism and to other parts) during development. Differential growth rates provide an explanation of many of the relative changes in position undergone by organs during development.

The size to which the foetus grows depends on the growth rate of the embryonic ceils, the amount of nutrition available and the duration of growth. The growth rate is controlled by genes and consequently the final size is genetically determined Environment also plays a part, maternal malnutrition being well known to cause smallness in the full term foetus. There is little evidence, however, to show that “excellent” maternal nutrition results in excessive size of the human foetus (see Burke et al., 1943 and 1949)- Ia the sheep, Wallace (194 ; as shown that the maternal diet in the first half of pregnancy has little effect on the size o c

♦ For detailed accounts of gro\vth sec D’Arcy Thompson (1942); Huxlev (1932), Needham (194-), Bro y (1945); Zuckerman el al (1950).



lamb at birth Diet of the e\se in the second half, honevcr, has a marked effect, high diets giving good Iamb growth, high birth weight and low neonatal mortality Post maturity with Its resulung increase in gestation time is alwavs associated with large size of the offspring The imtial amount of protoplasm m the egg would appear to ha\e little influence on final size m mammalian development Thus the egg of the whale is not much larger than that of the mouse

If any of the factors controlling growth arc increased or decreased the normal proportions of the body will be altered by the relative enlargement or reduction of the size of the organ con cerned Although later adjustments may correct some incongruities resulting from the disruption of the normal growth balance the scope of such regulations is strictly limited and beyond its range abnormalities of the growth processes become fixed as permanent malformations (Weiss 1939)


The pre natal development of the human body may be conveniently divided into three mam periods (i) the period culminating with implantation of the blastocyst but before the establishment of an intra embryonic circulation During this time, which occupies approxi malcly the first three weeks of pre natal life the foetal membranes are established and the germ layers are laid down m the embryonic disc {2) The embryonic period which extends from the commencement of the 4th week to the end of the 8th v\eek In this period there IS rapid growth and differentiation during which all of the mam systems and organs of the body and the major features of external body form are established (3) The foetal period extending from the end of the 2nd month until birth This is a pen^ of rapid absolute increment rather than of striking differentiation and the changes in external body form take place quite slowly through slight differences in the relative growth rates of the vanous segments and parts of the body (Scammon and Calkins 1929) The changes occurring m the first of these three periods have been described in Chapter IV The present chapter presents a survey of the changes in the external form and in spatial dimensions of the developing human organism from the 21st day of intrautenne life until full term and it is largely based on the embryos indicated m Table I, many of which are illustrated m Figs 97-109


Unless precise data of coitus and menstrual history which accurately dciennine embryonic age are available it is necessary to utilize the size and general features of development of an embryo in any attempt to estimate its age These measurements and features however, are extremely vanable and only give approximations to the real age (for details, see Streeter 1942) For purposes of comparison two or three measurements are usually employed They are (i) the aotxn rump (C R ) length (or sitting height) which is the measurement from the vertex of the skull to the breech (1 c , midpoint between apices of buttocks) , (2) the croun heel (C H ) length (or total length or standing height) (3) in embryos which are markedly flexed the greatest length or nech tump length is frequently used The C R and C H lengths arc given for embryos from the end of the 5th week m Table I In embryos at an earlier stage measurements are extremely variable because of the frequently marked flexures precise measurements therefore are not given in the Table In embryos between the commencement of the 4th and the end of the 5th weeks it is preferable to express the developmental stage in terms of the number of somites present In all attempts at estimating the age of an embryo the degree of development of its external features in addition to its length and weight must be taken into account

There is no absolutely accurate method of estimating the age of an embryo from its length for as has been indicated earlier there is considerable variaUon from one embryo to another (see Streeter 1942 1945 and 1948) The following rule however is useful in estimating the



approximate age: — at thirty-two days the embryo is 5 mm, G.R. length; for each additional f day up to the 55th day the embryo grows approximately i mm ; after the 55th day the daily i rate of growth is approximately r *5 mm. s'


Pre-somite Stage

See Appendix page 409

Somite Stage


Estimated age in days

Stage m development



I somite



4 somites



7 somites



10 somites



14 somites



20 somites

Carnegie No 6097


25 somites

Carnegie No 5923


28 somites

Development from the 5TH Week to the Commencement of the 3RD Embryonic

Month (1 e , 35-60 days)


Estimated age in days

C R length in mm

Carnegie No 5654


5 0

Carnegie No 6502


6 7

Carnegie No 6517


10 5

Carnegie No 6528


13 4

Carnegie No 6150



Carnegie No 4570



30 0

Growth in Length and Weight during the Foetal Period (i e , from the 3rd to the lOth embryonic month)

(Based on Schroder, Fehling, Mall, Streeter, Jackson, Scammon and Calkins artrl I observations)

Age (in lunar months)

C R length (i e , sitting height, in mm )

Total length (1 e , standing height, in mm )

Weight m grams


















(i e , approx j 13 inches)









(1 e , 20 inches)









(1 e , approx

7 pounds)

e that all these measurements show marked variation ocpe s nutritional and general environmental factors (eg, age ol mo of preceding pregnancies)

  • Tlie measurements and ages given m this table have been corrected m the have, however,

data They are mainlv based on the Developmental Horizon pubheauons o _ embrvos of known

modified some of his interpretations, which were derived bv human matcnal

age, in accordance with the information provided b> Hertig and Rock (1943)



external form of the embryo


The cfnbr}onic bod\ it the i^lh or lath da> after fcrtiltzauon conMsts of a bihminar disc of ectoderm and endoderm 1 > im, ren the ammotic and the t oJk. sac ca% i tics (I is;s 39 and 42) In the caudal half of the disc the pnmime streak can be seen m the midJmc as a linear thickeninq

s\ hich terminates antcnorlj in tlie pnmitnc (Hensens) node The presence of the pnmitnc streak toi^ethcr SMlh the nolo chordal process and the prothorda! plate confers an obsious bilateral sammetra on the disc Caudallj the primuise streak docs not quite reach the posterior ed^e of the disc bcin>, scparatctl from it l» the cloacal membrane (1 icj 4J> Ihepnmi ti\c streak stKin sho\\s a dntiiact primitive groove on its surface and antcrmrlv at the pnmitise knot the 5,TOO\e ts conimuovis With the blastoporal openm^ (Fiu 45) It IS obvious tint at this stapc none of the cinraclerivtic features nf the human bod\ such as head, neck trunk or limlis IS present

Uilli further t,roulh the einbrjontc disc increases in sire especially in the antero posterior a\is and the primiinc streak and knot ippear to be cametJ in a caudal direction (I tt, 4.^) During this process of apparent backssard migra Uon of the primitive streak the embryonic disi, changes ns shape and becomes first oval then pear sh iped and finally shaped rather like the Ixidy of a violin (Fig ftg) At the same time the embryonic disc as a whole is bulgm., upwards into the ammotic cavity and tli'TC arc slight head and tail folds (I igs 13-49) Towards the end of the presomite stage of development a broad anteroposterior groove appears m the neural plate ret ion of the embryonic disc in front of the primitive knot (Fig 49U;

fie 97 — Tlic donal aiprct of a rrronilrucUon of a 7 lomite human rmlirso of aUjul lU t c«l t!a ModifirJ from Pavnr (i»» 51 The carl) nptic lulcui ii jern in the prosencrphalic rci^ion \— pjrtiaif) setjmrntr t paraxial mrsoderm 11— roof f f neural tuliir O— tiericardial area D— branchial arch repion x c


This stage which c%tends approximately from the aoth to the 3oih da\ of human develop ment is characterized by the formation of sonutes In earlier stages tli'* paraxnl mesoderm lying on each side of the notochordal process « unsegmented As the embryonic axis grows the primitive streak „jves rise to additional paraxial mesoderm which heenmes divided successively into symmetrically arranged paired blocks called somites Tlic presence of these IS an indication of the fundamental mlamertsm of the body but it is important to note that typical somite formation never reaches quite to the level of the anterior extremity of tlir- nolorhordal process The somites increase m number with progressive development new ones beins, added



posteriorly until, generally, 43 or 44 pairs (4 occipital, 8 cervical, 12 thoracic, 5 lumbar, 5 sacral, 8-10 coccygeal) are formed. The somites are conspicuous features of embryos in the stage under consideration and are readily seen even in unfixed material They are the basis from which the greater part of the axial skeleton and musculature are developed (Their further history is described in Chapters XIII and XIV.) Embryos at successive periods during the somite stage are shown in Figs. 97“^°3 ^43 Boyden (194°) given a volumetric analysis

of 10- and 1 2 -somite embryos.









Fig. 98 — The dorsal aspect of a reconstruction of a lOsomite human embryo of about the 23rd day Modified from Corner (1929) The bulge visible on either side below the mandibular arches is produced by the pericardium The elevations on the yolk sac wall are due to blood islands x c 40

















Fig 09 —The left lateral aspect of a reconstruction of a ®4.somite human embryo of about the 25th A/fr»rIifipd from PTeuser (JQ 5 ^) ^

In an embryo with one pair of somites (Ludwig, 1928), the embryonic ® as that

and has definitely advanced from the condition shown in a late . 1 extremity

of Heuser (Fig. 45). . In particular the greater breadth

of the neural plate is noteworthy. The primitive streak and P ecto feates a. .h/cauda. end B? .he inort

dermal boundaries of the neural groove (neural folds) have b


jn the region of the fourth to se\enth somites base fused dorsall^ to enclose a neural canal The head and tail folds ha\e become much more prominent (I ig 78) the former ha\ mg on its dorsal aspect the broadened neural plate svhich will become the future pTOsencephalon (fore bram) with its optic sulci while the latter has carried the primiti\e streak and tail bud to the posterior end of the embrsomc axis The caudal end of the neural groove IS now embracing within its folds the anterior end of the pnmitive streak and blastopore In a to somite embryo (Fig 98) the closure of the neural folds has progressed anteriorly m front of the somite region to the area which will become the mesencephalon (midbrain) and postenorly beyond the level of the loth somite The unclosed anterior and posterior ends of the incomplete neural tube are now known as the anterior (Fig 99) 3 iid posterior neuropores The head fold is much more marked and underlying it on either side can be seen a svvelling ihe mandibular arch produced by the underlying branchial mesoderm which is bounding the primitive mouth or stomatodaeum Ventro lateral to each mandibular arch is the bulge due to the developing peneardium and heart Fig 99 shows a 14 somite embryo (Heuser 1930) from the left side The anterior and posterior neuropores have become further reduced in swe ow ing to the progressive closure of the neural groov e From the lateral aspect the extent of the head and tail folds IS well shown The line of attachment of the amnion to the embryo is nov-. relatively reduced m size and has been carried well on to its ventral aspect The head region now shows certain marked features — the maxillary and mandibular processes (bounding the stoma todaeum) and the hyoid (and pharyngeal) arch can now be identified Between the mandibular process and the hyoid arch the depression of the first pharyngeal {branchial) ectodermal grooie is seen and caudal to the hyoid arch the second pharyngeal grooie A thickening of the ectoderm dorsal to the second pharyngeal groove marks the position of the otic placode Ventral to the pharyngeal arches is the pericardial elevation

In the 20 somite embryo (Davas 1923) two aspects of which are shown m Figs loo and loi the anterior neuropore is closed and the region of the forcbrain projects markedly the posterior neuropore is stiU open Ventral to the forebram is the stomatc^acum, bounded on either side by the maxillary and mandibular processes Between these processes laterally and the forebram above and the pericardium below is the bucco pharyngeal membrane which is m the process of rup turmg to establish communication between the stomatodaeum and the foregut The pericardial swelling is now very prominent the 3rd pharyngeal

Fig ioo — The lateral aspect ot a reconstruction of the head and upper part of the trunk of a 20somite human embryo of about 26 days Modified from Davis (1923) X c 32

human embryo of about 26 days Modified from Davis (1923) X c 32

1 10


arch is appearing and the otic placode of earlier stages has now become the otic depression. A ventral view of the tail fold now shows the cloacal membrane (Fig loi). The connexion between the^midgut and the yolk sac has become further constricted and is surrounded by the wide open communication between the intra- and extra-embryonic coeloms

In late somite embryos (e.g , 25 and 28 somites, Figs. 102 and 103) both neuropores are completely closed. The whole embryo is .more elongated and markedly curved, with the attachments of the amnion and yolk sac relatively much reduced on the ventral aspect so that an umbilicus and umbilical cord can now be recognized. The pharyngeal region is further advanced in development and the 3rd arch is well established; the optic vesicle can now be seen through the overlying ectoderm and, by the 28-somite stage, the otic depression has separated from the surface ectoderm to form the otic vesicle. The attenuated tail, with its somites, reaching the region of the umbilical cord is a feature of these stages


During this period of development the<embryo passes from a stage of about 5 mm. C.R. length at the 32nd day (Fig. 104) to a stage of about 30 mm. at the 55th to Goth day (Fig 109). At the begmmng of the period the somites can still be recognized and, indeed, continue to be formed until the 1 1 mm. stage, but are no longer conspicuous. Paired arm and leg buds soon make their appearance (Figs. 104 and 105), the former slightly earlier and at the level of the pericardial swelling, the latter somewhat later and just caudal to the level of attachment of the umbilical cord. The anterior end of the head region is now bent downwards towards the pericardium and the head is markedly flexed on the trunk at the so-called cervical flexure. The neck. Itself, however, has not yet appeared. The optic and otic vesicles can be seen and the roof plate of the rhombencephalon (hindbrain) appears thinned out above the pontine flexure (Fig. 105). The pharyngeal (branchial) arch region has now become elevated from the pericardial swelling and an epipericardial ridge is situated between the two regions The pharyngeal arches themselves are more distinct and, even at the 6 7 mm. stage, the hyoid arch is overlapping the 3rd arch, and succeeding arches, to enclose the ^‘cervical sinus” The olfactory pit is now visible on the lateral surface of the anterior cephalic region above the stomatodaeum

By the 105 mm. stage (Fig 106) the pharyngeal region has become much modified. The maxillary process passes forwards beneath the optic vesicle and is fusing with the lateral surface of the lateral nasal fold. The first pharyngeal groove is deeper and is differentiating into the external auditory meatus The upper limb bud now shows its primary differentiation into arm, forearm and hand while the hind limb bud still retains its primitive “paddle” shape. The tail IS undergoing retrogressive changes '

In an embryo of 13-4 mm C R. length (Fig. 105) the principal features are the marked increase in the size of the head, accompanied by a decrease in the ventral flexion of this region, and the appearance of obvious forebrain vesicles. The pontine and cervical flexures, however, are more marked. The first pharyngeal groove is even deeper and the rudiments of the externa ear are appearing on the surfaces of the mandibular and hyoid arches The more anterior somites can no longer be recognized, having lost their identity in the fusion and growth c they have undergone The hand now shows the outlines of the future digits and the eg u has divided into thigh, leg and foot regions. The area of the ventral body wall a ove t e attachment of the umbilical cord is bulged ventrally by the liver and above it y t e more translucent pericardial area through which the heart can in part be seen nx i j

By the 46th day, when the embryo is of about 17 mm G R length (Fig. 10 ), t e ea rerion has increased even further in size and, as the neck region is developing, is ess •

Fvehds are just commencing to form, the external ear is becoming apparent ^ ^

auditory meatus and, as the downgrowth from the hyoid arch has fused with t e si e o e ^ ’

cS sinus has become obliterated. The digits of the hand are separating, but those f t>ie foot still appear as united rays At the end of the 2nd month, in an embryo o 3 •

G R length (Fig. 109)5 characters have been assumed which mark the em 3 ryo e ni y


1 14

human The neck region- has become established with resulting partial extension of the head (cf Figs 108 and 109) The eyelids are more obvious and the external ear is apparent. The umbilical cord is relatively reduced in size and is now attached more caudally on the anterior abdominal wall ^vhlch is less protuberant The limbs are in the embryonic position, with the pre-axial borders (radial and tibial respectively) directed cephahcally, and the digits of both hands and feet are clearly defined The tail has now almost completely disappeared

Fig 108 — A photograph of the left side of a Fig 109 — A photograph of the left side of a

17 mm CR length human embryo (estimated 307 mm CR length human embryo (esti age, 46 davs) X c 4 7 mated age, 60 days) X c 2 6

Development of the Face in the Second Month. The development of the facial region dunng the 2nd month is dominated by the changes resulting in the formation of the nose In a 6 mm embryo (Fig no) an epithelial thickening, the nasal or olfactory placode, appears on either side of the front of the head above the stomatodaeum Initially the placodes are convex and not sharply circumscribed but soon (Fig 105) they commence to sink in to form the gradually deepening olfactory pits This sinking m of the placodes is due not so much to their own depression as to an elevation of the surrounding ectoderm due to the proliferation of the adjacent mesenchyme The elevations resulting from the mesenchymal growth are more marked at each side of the pit and in these positions are called the medial and lateral nasa folds The medial nasal folds together with the intervening area above the stomatodaeum form the so-called fronto-nasal process (Fig. in) Each lateral nasal fold separates the corresponding olfactor\' pit from the developing eye The fronto-nasal process and the maxillary and mandibular processes of each side are the elements from which the face is developed The anterior extremities of the mandibular processes fuse to form a complete lower jaw at about the 5 mm. stage. Each maxillary process grows anteriorly from the dorsal portion of the corresponding mandibular arch and fuses wath the low-er lateral edge of the lateral nasal process, it then exten s be\ond this across the lower margin of the olfactory pit, which can now be called the anterior



nans to reach and fuse with the medial nasal process (Figs ill ii2 and 113) Eventually it appears to fuse with its fellow of the opposite side m front of the lower portions of the medial nasal processes (Frazer 1931 Bo>d 1933) (Fig 114)

Dunng the stage when the facial processes are developing and fusing well marked grooves are found between them The cleft between the mandibular and maxillar> processes is the

pnmitiie mouth and it decreases in trans verse extent dunng the and month owing to fusion of the posterior parts of the processes to form the checks (cf Figs 1 12 and 114) The groove between the maxillary process and the lateral nasal process extends from the antenor angle of the developing eye region to the mouth, and as u repre sents the line of development of the najo lacrimal duct it is called the naso lacrimal furioa. The grooves between the different facial processes normally disappear soon after the 20 mm stage but may persist as furrows or deep clefts between the constituent parts of the face in such conditions as hart bp and congenital facial cleft (Fig 176)

\N hile the facial processes are increasing in size and fusing the olfactory pits become deeper and more extensive forming the prmilue nasal eaiities and the external or anterior nares come to lie nearer to each othei (cf Figs 112 and 113) At about the j 6 mm stage a transverse furrow appears between the nasal region of the fronto nasal process and the frontal region so that the nose can be recog nized (Fig ria) Its tip is indicated by a rounded elevation above the external nares which are now closed by plugs of proliferated epithelium At the end of the 2nd month the nose is represented by a definite eminence

•Vt the beginning of the 2nd month the future lens of each side can be rccogmzed as an area of thickened ectoderm — the lens placode — overlying the optic vesicle (Figs 104 and no) Each lens placode soon separates from the surface ectoderm (page 319) to form the lens Pigment which appears m the optic vesicle at about the 10 mm stage soon becomes a striking feature and can be readily seen through the covering ectoderm (Fig 107) The

Fic no — A drawing of the lefl vemTO*\ateral aspect of head end of a C mm human embryo (after Streeter 19 a) X c ig

Fio III —A drawing of the ventral aspect of the laceofa 10 mm human embryo


1 16

eyelids arise as arch-like folds of the ectoderm above and below the developing optic cup and lens at about the 1 8 mm stage (Fig 114)

The external ear also appears in the and month in the region round the first pharyngeal ectodermal groove In the 6 mm embryo (Fig no) this groove is bounded by the smooth lips of the mandibular and hyoid arches. By the 9 mm stage (Fig 106) these lips show surface irregularities which can be identified as hillocks in 12 mm. embryos (Figs 107 and 112) By growth and fusion the hillocks and the immediately surrounding areas give origin to the primitive pinna (Fig 114) This, therefore, is situated around the developing external auditory meatus ivhich represents a persisting part of the ist pharyngeal groove. There is difference of opinion as to the relative contributions made by the hyoid and mandibular arches to the pinna but the greater contribution appears to come from the hyoid arch (Streeter, 1922, Jones and I-Ghuan, 1934), only the tragus and the area immediately surrounding it being derived from the mandibular arch The nerve supply to the adult ear supports this interpretation When the ear first

Tig 1 12 — A draiMng of the left ventio-lateral aspect of a model of the head of a 12 mm human embryo (after Streeter, 1922) X c ii 5

Fig 1 13 — A drawing of the left ventro-lateral aspect of a model of the head of a 14 mm human embryo (after Streeter, 1922) Xc 114

appears it is situated ventro-medially, but with the development of the lower jaw and face during the second month it is gradually displaced dorso-laterally (cf Figs 107 and 109)

While the superficial aspects of the mandibular and hyoid arches are undergoing the changes resulting in the formation of the pinna, the more posterior pharyngeal arches remain small and come to he m the depths of a retro-hyoid depression — the cervical sinus (Fig. 105) By growth changes which appear to involve principally a backward extension of the hyoid aich this sinus is overlapped and eventually, by the 18 mm. stage, obliterated (cf. Figs. 106 and 107; also this region in Figs 108 and no— 112) As this process results in the enclosing of some surface ectoderm the latter may persist to give rise, in later hfe, to an ectodermal branchial c>st or fistula (see page 197),

By the end of the 2nd month the face has assumed human characteristics with a wellestablished nose, complete upper and lower lips, cheeks, a small mouth, eyelids and a recognizable external ear. The obliteration of the cervical sinus gives a smooth contour to the neck in the region formerly occupied by the lower branchial arches




It IS customary to use the term for the embryo in this period The distinction is

arbitrary, but it is useful m that it emphasizes the acquwiuon by the embryo when it reaches this stage of all the characteristics which can be recognized in later development and post natal life The term might be defined as the stage at which the generic identity of a mammalian embryo can be readily recognized The human embryo takes on an unmistakably human appearance at this time As the distinction is an arbitrary one there is no precise time when the term foetus should first be used, but the commencement of the 3rd month is convenient and usual

During the 3rd month the foetus grows rapidly, nearly doubling its length, and most of the parts of the body reach their defimtivcfoetal positions The head however remains rela tively large and even by the end of the month IS about one third of the C R length (see Fig 1 15) The rump region and the legs are relatively small while the tail completely dis appears partly by retrogression and partly by absorption into the rump The forehead is high and prominent and as a result of the broadening of the vvhole facial region the eyes which in earlier stages were directed laterally, are now situated more anteriorly The external ear also undergoes a relative change m position so that by the end of the 3rd month it lies on a level with the lower jaw In the earlier part of the 3rd month the eyelids grow rapidlv and by the 35 mm stage their free margins arc usualU joined by epithelial fusion and are represented merely by a transverse furrow In the early part of this month the first rudiments of hair appear These are the so called vibnssal hairs and are found sparsely scattered m the eyebrow region in the upper lip and curiously at certain points in the extremities, especially in the carpal and tarsal regions Later they also appear on the skin of lovset hp Towards \he end of the jrd monib a much more extensive crop of very fine foetal hair fanugo ippcars m the region of the forehead and eyebrow vibnssae During the month the trunk region becomes relatively moreshm the liver region is less protuber ant and the hernia of the midgut into the extra embryonic coelom in the region of attachment of the umbilical cord (Chapter X) is withdrawn ( reduced ) apparently quite suddenly about the 42 mm stage The externa! genitals during the 3rd month undergo marked changes and by ibe 50 mrn C R length stage it is possible to identify the sex of a foetus by external inspection By the end of the 3rd lunar month the upper limb has assumed a length relative to the rest of the body which remains more or less constant for the foetal period and the hind limb assumes definitely human charactensUcs (Fig 115) Nails are now well indicated by furrows

In l nglish and coniinentat litcrature/„fttf is u ual *n American fetus Etymotocically vhete is no donbi .k spelling fetus the word being related to fehx femina etc The^ incorrect speUine occun fim

(57i>-;636 ad) who fancied that the word could be derived Irom foiei (I chcruhl 7^' mistake iw bem followed by later nnters and so has passed into current



on the dorsal aspect of the tips of the fingers. The lower limb is less well developed, the toes are still spread out fanwise (Fig 109) and the nails are only represented by slight furrows By the end of the 4th lunar month (Fig 1 1 6) the embryo has a sitting height of about TOO mm, and individual differences can now be recognized (eg, m unlike twins). The face IS relatively broad and the eyes widely separated A few true hairs are present m the lower

Fig 1 15 Superimposed photographs of foetuses between the 3rd and 5th months of pregnancy (Original )

frontal region but the carpal and tarsal vibrissae have retrogressed. The attachment of the umbilical cord is still just above the symphysis pubis region

At the end of the 5th lunar month (Fig. 116) the embryo has a sitting height of about 130 mm Its total length is approximately 228 mm which is about half the total length of the full-term foetus Its weight, however, is still less than 500 grams The mfra-umbilical

cROW'iH oi iin iMntno


region of the ilKlomcn iK-cotnrt ippirrnt with multing nlfrniion of tlic itincliincnt nf tlic umbihc-il cori! Hie lower limlw h-we incffvol coniidenliK in length hut tlic\ nrc still shorter thin the upper It is clurini, the 5lh month tint f*x-til ino% ments ( quid/mi; ) are iisuilU Tint dciectnl Iw the mother 1 me Inir Iinugo is now present over most of the l)od> me! is the selnceous gbnds l>ecome irtive srhiiin ippeirs on the sbm surfiee

During the sfcnml Inlf of miri uterine life tlie totil length of the foetus inrreises 1)\ iIkhii 5 cm monthh Ilie weight howeser, tnemes much more npidlv (1 ihle 1; so tint the 300 grams of the jth month becomes over grinis it full term

Hn tlie end of the fith month (Iig iiO) the ficc is more infint hVe the linugo hair IS darker md the evebrows and c}eluls ire well defineil The lower part of the interior alxJommal will his incrcise<I m length The skin is chiricter islicil!^ verj wrmkle<l it this Ii iif - \ f>fi (<rni tx rf ili i untin fwtui fr m the

time due pretlimibl) tout Jlii (I <tll> la.e I on V.mmon

growing more ripidl> thin the iindcfl)ing connective tissue

At the end of the 7th lumr month (lig ilO) owing to the tlrjiosuion of subciilineout fit the foetus Ins vsell rounded contoun md the ssnnlded skin is lost Ihe hiir on the held becomes longer the face more infint like mil the e>eli(ls ire no longer fuseil A child Ixirn at this stage can with circful ittcntion survive le itisvnble 1 lierc ire hovsever recortls of survival of cliildrcn Imm it in even rirlicr stage

Dunng the fllh md gth lumr months the sul>ciitmeo«s tissues l>eromc thicker md the skm which IS ilso thicker is now vimforinl^ covered with the rern« raicoia 1 mnture of sebum and desquamited epitlieln! cells which possiM> protects the skin from the micerilm^ effects of the liquor amnii 1 he Inir on the hcid is novs much thicker mil longer thin the generil Imugo hair wluch is beginning to disippeir The lower extrenmj is relitisely longer ilnn in eirlier stigcs but his not >ct eqinlled the length of tlic upper eitrcmitv I he finger mils rcich the finger tips during this perioil but the toe mils ire shorter Tlic left testis imv be m tlic scrotum

During the loth lumr month the roclus liccoines even plumper the hnugo Inin of the body disippear except possibly in the scipuhr region the mils project beyond the tips of the fingers and have readied the ends of the Iocs Ihc lower extremity grows ripidly, hut even at full term it is not is long as the upper Ihc ihomx Iwcomcs wider md the growth of the infra umbilical region brings the ittichmeni of the cortl to 1 point ncir the centre of tlic anterior abdomiml vsiU

The last two months of foctil life irc appircntly devoted more to 1 gcncnl * building up of tissue than to the cstibhshmcnt of any new tissue or orgm Survivil of foetuses born at the 8ih month is not uncommon, though of course mittirily ii birth gives 1 better chmec m post natal life As Smith (igjG) Ins pointed out however humm foetuses ‘

in some



aspects warped from the standard pattern by this extra post-developmental uterine sojourn.”

At birth the full-term child normally weighs a little over 7 lbs. (3000 grams), although any weight between 5 and 10 lbs. is within the normal range. Heredity appears to be more significant in determining the weight of the full-term foetus than does maternal diet (see, however, Chapter VIII), The total body length is about 20 inches (50 cms ) ; the sitting height (i e., C R length) about 12-13 inches. The circumference of the head is also about 13 inches. The circumference of the chest is normally rather less than that of the head and the circumference of the abdomen at the umbilical level approximates to that of the chest. The arms and the trunk are longer than the legs. In male infants both testes are normally in the scrotum at the time of birth The reflex activity of the new-born child is considered in Chapter XII.


Boyd, J D (1933) The classification of the upper hp in mammals J Anal , Land , 67 , 409-416 Boyden, E A (1940) A volumetric analysis of young human embryos of the 10- and 12-somite stage Conlrtb Embry ol , Carnegie Inst. Wash , 28 , 15 7- 192 Brody, S (1945) Bioenergetics and growth. Remhold, New York

Burke, Bertha S , Beal, V A , Kirkwood, S B , and Stuart, H C (1943) Nutrition studies during pregnancy, Parts I, II and III Am J Obsl Gynec , 46 , 38-52

Harding, V V, and Stuart, H C. (1943) Nutrition studies during pregnancy. Part IV J Pediat ,

23 , 506-515

Stevenson, S. S., Worcester, J , and Stuart, H C (1949) Nutrition studies during pregnancy. Part V.

J Nutrition, 38 , No 4, 453-467

Corner, G W (1929) A well preserved human embryo of 10 somites Contrib. Embryol , Carnegie Inst Wash, 20, 81-102

Davis, C L (1923) Description of a human embryo having 20 paired somites Contrib Embryol , Carnegie Inst. Wash , 15 , 1-5 1

Fehling, H (1877) Beitrage zurT^ys'ologte des placentaren Stoffverkehrs Arch f Gynak , 11 , 523-557 Frazer, J E (1931) Manual of Embryology Bailliere, Tindall & Cox, London

Heuser, C H (1930) A human embryo with 14 pairs of somites Contrib Embryol , Carnegie Inst Wash, 21 , 1 35 - 1 54

{1932) A presomite human embryo with a definite chorda canal Contrib Embryol , Carnegie Inst Wash.,

23 , 251-267

Hu\le>, J S (1932) Problems of Relative Growth Methuen, London

Jackson. C M (1909) On the prenatal growth of the human body and the relative growth of the various organs and parts Am J Anal, 9 , 119-165

Jones, F W , and I-Chuan, W (1934) The development of the external ear J Anat , Land , 68, 525-533 Ludwig, E (1928) Tiber einen operativegewonnenen menschhchen Embryo mit einem Ursegmante (Embryo Dal) Morphol Jahrb , 59 , 41-104

Mall, F P (1918) On the age of human embryos Am J , 23 , 397-422 Needham, J (1942) Biochemistry and Morphogenesis Cambridge TJniv Press, London Payne, F (1924) General description of a 7-somite human embryo Contrib Embryol , Carnegie Inst Wash, 16 , 1 1 7-1 24

Scammon, R E , and Calkins, L A (1929) Development and growth of the external dimensions of the human body in the foetal period Univ Minnesota Press, Minneapolis Schroder, K (1869) Tiber die Verschiedenheiten in der Grosse der Kopfe Neugeborener Kinder Beit Z. Geb u Gyn , 5 , 401-42 1

Smith, C A (1946) Physiology of the Newborn Infant Thomas, Springfield, 111

Sternberg, H (1927) Beschreibung eines menschhchen Embryos mit vier Ursegmentpaaren, nebst Bemerkungen uber die Anlage und fruheste Entwicklung einiger Organe beim Menschen Z^its J Anal , u Ent , 82 , 142-240

Streeter, G L (1922) Development of the auricle in the human embryo Contrib Embryol , Carnegie Inst. ITflj/; , 14 , 111-138

(1942) Detelopmental horizons in human embryos • age group XI, 13-20 somites, and age group Xlt,

21-29 somites Contrib Embryol , Carnegie Inst IVarA , 30 , 21 1-245 ,

(1945) Developmental horizons in human embryos age group XIII, embryos 4 or 5 mm long ana

age group XIV, indentation of lens vesicle Contrib Embryol , Carnegie Inst Wash , 31 ,

(194^) Developmental horizons m human embryos age groups XV, XVI, XVII and XVIIl, being

the third issue of a sur\'ey of the Carnegie Collection Contrib Embryol , Carnegie Inst Wash , 32 , i 33'^*^3 Thompson, D’Arcy (1942) On Growth and Form Cambridge Univ Press, London t a ,r

Wallace, L R (1948). Growth of lambs before and after birth in relation to the level of nutrition J Sci , 38 , 243-302.

Weiss, P. (1939) Principles of Development Holt, New York

Zuckerman, S , et al (1950) A. discussion on the measurement of growth and form Proc Boy ooc , >





During development growth processes are usuall> associated with an increase m the complexity and organization of the cells involved Thus the increase in size is accompanied b} an increase not onlv in the number of cells (b> multiplication) but also in the number of varieties of cells This appearance of new kinds of cells is called differentiation Tlic nature and causes of this progressive differentiation dunng development arc amongst the fundamental problems of embryology Differentiation of cells or tissues may be and in fact usually is established ( invisible differentiation) before it is manifest and morphologically apparent The elucidation of the earliest phases of differentiation has been a major achievcmentol experimental cmbrvology


In modern embryology an idea fundamental to the study of differentiation is the concept oC deteminalm, i e the fixation at a definite lime in development of the fates of different parts of an embry o Before the dev elopmental fate of a part of an embry o has been fully fixed and while It is still in the plunpoltnl or plcstu staff, it is said to be undetemmd The early experimental work of Roux (1888) on amphibian development in which one of the first two blastomeres was destroyed with subsequent development ofa half embryo from the uninjured cell gave nse to the concept that the egg had a mosaic pattern and that the fates of all its parts w ere determined at the onset of development In 1891 however Driesch obtained complete though small larvae from single blastomeres isolated at the two cell stage of the sea urchin egg Later he showed that whole embryos could be obtained from single blastomeres isolated at the four cell stage or from fusion of two eggs into one This vvork demonstrated that for the sea urchm egg a strict mosaic does not exist at the time of fertilization as portions of xn egg can regulate to produce a vvhole embryo Driesch introduced therefore the term prospretue significance to indicate the actual fate in normal development of any part of the original egg As his experiments had demonstrated that the potential fate of any such part is not exhausted by its prospective significance he suggested the term prospecUie poUnty to indicate the possible fates of the part under consideration In normal development the actual fate (the prospective significance) of a cell or group of cells is that chosen from among the possible fates (the prospec live potency) of that cell or that group of cells One of the most fundamental processes in development is in the progressive restriction {1 e determination) of the possible fates of the different parts of the egg and blastula as development proceeds It will be seen that prospective sigmficance which deals with the normal fatcof individual cells or cell aggregates is pnmanly a morphological concept Prospectiv e potency on the other hand, is chiefly a physiological concept concerned with the regulative oradaptative potentialities of cells or cell aggregates The investigations of Spemann (summarized m 1938), utilizing the method of grafting small portions of embryos to other embryos or to different regions of the same embryo have shown that up to a certain stage of gastnilauon the fates of most of the embry omc regions except that of the blastoporic region are undetermined so that if a portion of one presumptive region is grafted into another region of different presumptive fate it will develop m conformity with the developmental fate of the receptor region ( neighfaourwisc Needham 1942) During 121



the process of gastrulation this pluripotency, or plasticity, becomes restricted so that the main fates of the different parts are irrevocably determined and a transplanted portion grafted after this stage develops m accordance with its own prospective significance (“selfwise”) In other words, during the process of gastrulation “prospective potency has been ruthlessly curtailed to prospective significance” (Needham, 1942).

The term segregation is occasionally used to mean the separation and isolation of particular potencies, 1 e , the restriction of the developmental potentialities of a part to its prospective significance and the initiation of self-differentiation by deterrmnation The use of the term in this sense is not necessary and should be avoided (Needham, 1942).* In descriptive embryology it may be used, however, to describe in a general sense the process whereby collective distinction is conferred upon groups of cells which will give rise to a particular embryonic layer, tissue or organ The term is used m this sense m this book.


As has been stressed by Weiss (1950), it is convenient to restrict the term "‘differentiation^' to the appearance of intrinsic and irreversible differences amongst strains of cells. Differentiation must be contrasted with “modulation," which is the term Weiss suggests for the varying and often reversible changes occurring m cells m response to different environments The critical test for determining whether or not differentiation has occurred is transference of the cells m question to a controlled environment, as in tissue culture. If the cells revert to a common type they have not undergone differentiation. The occurrence of irreversible (i.e., true) differentiation in the course of development is an acknowledged fact, nevertheless its occurrence in any particular instance can only be established empirically (For discussion see Medawar, 1947, and Weiss, 1950 )

Differentiation can be conveniently divided into —

{a) invisible differentiation (or chemo-differentiation), when the differentiation is determined, but IS not yet apparent microscopically,

[b) histo-differentiation (tissue differentiation), when visible differences appear and the characteristic cytological and histological appearances of the tissue into which the group of cells concerned is developing can be recognized ,

(c) auxano-differentiation (differentiation during later growth), the period during which the organs become modified by growth and alterations in proportions and begin to assume their adult appearance. During this period specific function is established

During periods of rapid differentiation the mitotic activity of the cells concerned diminishes and, in general, there is a loss of mitotic activity as differentiation proceeds The power of regeneration of a tissue or organ is inversely proportional to the degree of differentiation of the tissue or organ. Further, regenerative ability is much greater in animals lower in the evolutionary scale than m higher types.


One great difficulty in the way of the complete acceptance of the idea of the loss of potency during development is the fact that during certain developmental changes, in repair an regeneration, and in many pathological processes (e g , tumour formation) certain cells appear


♦ The plethora of terms used in experimental embryology is a great disadvantage to the study o a real bane to the student In this subject, to quote Medawar (1947) hypothesis often tends P

fact beyond a calling distance, and the subject as a whole is sustained by a huge variety of P. 1^

terms . Needham (1942) has cut away some of this undergrowth already,, some terms ^ an

on sufferance, and there remains a residue of useful and contectually necessary terms in tn 1 attempt has been made to restrict as far as possible the use of unnecessary terms


to revert to a more pnmim c t\pe This apparent reversion to a simpler vanct> of cell is called dedtfferenltalion Many investigators believe that it docs actuall> occur and consider that cells can dcdifTerentiate or rcdifTerentiatc in reaction to an altered environment Others however, consider that phenomena of this nature can be explained bj the persistance m most, or all tissues of cells which are essentially non diircrcntiatcd and that it is these undifTcrentiatcd cells which are involved m the processes of repair and regeneration It is generallv recognized that the reversion is more likcl) to occur in tissues composed of less well dincrcntiatcd and organized cells Vcr> highl> dtficrcntiated tissues (eg, mammalian nerve cells) show little evidence of dcdiffercntiation

The term metaplasia is often used especially in pathological literature to describe the transformation especially postnatal of the cells of one tvpc of tissue into those characteristic of another ^Vhether it occurs by dedifTcrcntiation of the cells of the original tissue into a more pnmitive cellular type with subsequent rcdiflcrcntiation into the new varietv or by the direct transformation of the original cells to another specific cellular tvpe is not vet satisfactonlv established


One region of the amphibian embryo was shown by Spemann and Mangold (1924) to be determined at a very early stage possibly at the time of fertilization and it is, therefore very much less plastic than the rest This is the dorsal region or lip of the blastopore which in the later stages of gastrulaiion gives ongm to the notochord and mesoderm The dorsal lip region develops selfwase and m no direction other than its normal presumptive fate Further if all or part of it is grafted into the undetermined tissue of mother blastula or early gastrula the neighbouring host cells irrespective of their presumptn e fates are caused to form or to attempt to form the tissues of a secondary embryo On the other hand in the absence of the dorsal lip region from an early embryo normal development does not occur The forma tive influence exerted by the blastopore cells on neighbouring cells is called induction Since the blastopore cells apparently contain vvithin themselves the ability to determine the fates of regions with which they are m contact Spemann called the dorsal lip region the primary organijr because it is apparently the first of such mechanisms to function m development Further analysis of the primary organizer has shown that m vertebrates it can be divided into Ahead organiser (consisting of the cells which arc first invaginated and which form the so called pro chordal plate see Chapter VI) and a trunk (sometimes called tail) organizer which is constituted by the later invaginated chorda mesoderm

The concept of organizer activity has been applied to many other stages of development and secondary (second grade) tertiary (third grade) etc organizers have frequently been described as being concerned with the initiation and control of many if not all, of the processes of early histogenesis and organogenesis While this concept has played a useful role in the study of development recent opinion indicates that it is an over simplification of the compli cated phenomena In particular it must be stressed that organizer phenomena arc not simple single unitary and elemental processes (^Velss) The brief summary of organizer activity which follows here must consequently not be taken too rigidly

Individual organizers do not usually retain their ability to influence the developmental changes with which they arc concerned for more than a limited period of lime during which the cells or tissues upon which they produce their elTects arc said to be competent to react to the organizer influence (Waddington 193a) Competence (or reactive potency), then is the ability of a tissue to react to a developmental stimulus The inductive effect of an organizer usually results in the production not only of a particular tissue (eg neural tissue or lens of eye) but also m the determination of the regional character of the resultant tissue (e g if neural tissue IS concerned, midbrain or spinal cord) In other words induction results in two types of determination presence of a particular tissue and the character which that tissue adopts For the former type of determination Needham and others {1934) have suggested the tem



evocation, for the latter type individuation Evocation consists of the changes (usually histological) produced by the action of a chemical substance {evocator) produced by the organizer. Individuation IS concerned with the regional orgamzation of the embryo or embryonic tissues and m addition to the activity of chemical substances possibly involves the action of so-called ’’'field-forces” (see later)

The activity of the primary organizer is presumably due to the presence of a chemical substance m the cells of the dorsal hp region. This evocator substance can be regarded as a morphogenetic hormone which passes by diffusion from the blastopore cells, or their developmental derivatives, to other cells where it modifies the rate of development and the direction of differentiation Chemical study has been restricted chiefly to the substance produced by the primary organizer in Amphibia and to that particular aspect of its activity concerned with the determination of ectoderm to form neural plate. Spemann (1931) demonstrated that after crushing of its cells the dorsal lip region could still induce neural plate formation. Later Spemann et al (1933) and a number of other investigators showed that induction by the organizer region was still possible after it had been boiled Later work (see Needham, 1942, for details) demonstrated that the activity is probably due to a chemical substance of a steroid nature which has a similar structure to the carcinogenic polycyclic hydrocarbons, vitamin D, the sex hormones, corticosterone and the bile acids. The steroid nature of the ” neurogen,” as the primary organizer is sometimes called, has not yet been definitely proved It is particularly interesting that the primary organizer and certain of the secondary ones are not species specific, thus chick blastopore will induce a secondary embryonic axis if introduced into an amphibian blastula

While the analysis of evocator action m terms of a morphogenetic hormone is essential in a first approximation to a science of causal embryology and has proved of great utility in the establishment of the primary principles of this science, simple cause and effect relationships are not adequate, at present, for the interpretation of the totality of the interactions concerned in development A number of investigators, therefore, basing their speculations on conceptions of great significance m modern physics, have supplemented the idea of organizer activity in development by that of “field forces.” This conception of developmental fields is utilized, for example, in the explanation of that type of determination involved in the regional organization of the embryo and which has been called individuation The field concept of the developing organism regards it as a structure m which the whole and the parts are dynamically interrelated and are continuously reacting to each other and to the totality of their environment. In the earlier stages of development the different parts of the embryonic morphogenetic field can be regarded as unstable, but in subsequent development the instability is continuously giving place to stability, as plasticity of a part becomes replaced by permanent fate

The concept of morphogenetic fields, and that special and restricted modification of it which Child (1941) has elaborated in the idea of physiological gradients, have been useful in many problems of embryology. It cannot yet be decided, however, whether such field forces are a sigmficant biological concept or are an expression of our present ignorance on the inter-relationships of the evocator mechanisms.


The concept of the three primary germ layers has had a very considerable influence on the growth of embryological knowledge. From the teaching point of view, particularly, it has been extremely useful and a knowledge of the derivatives in normal development (Chapter ) of each of the germ layers is essential for the understanding of descriptive embryology. The results of modern experimental embryology, however, have rendered untenable too rigid an adherence to the concept of the absolute specifiaty of the germ layers The germ have a topographical significance and their formation, m a teleological sense, “seems to be t e embrj'o’s method of sorting out its constituent parts” (Oppenheimer, 1940). “In reali y.


the germ Ia)ers like the blastomcrcs, have an actual poicntiahtj and a total potcntia!it> the former is what the) nonnall) become the latter what thc> arc capable of forming m addition under diverse natural or experimental influences (Brachet 1935) It has been emphasized b) McCrad} (1944) however that much of the difficultv disappears if care is taken not to use the names of the germ la>ers before differenuation has occurred ic to distinguish clearlv betvieen prospective germ la>eis and definitive germ lavers \tcCradv stresses that while there ma) be a labile or plastic stage in the earlj precursors of the germ lavers there is alwavs a mosaic stage m which the la>crs arc ngidlv determined This mosaic stage is the basis of the significance of the germ lasers m the phvsiologv of development

Some cmbrjologists indeed, make a distinction between the germ lajcrs still capable of further segregations and those which have reached the end of their cmbr>onic evolution For the former the suffix blast is used for the latter the suffix derm Thus in the vertebrates generallv at the end of gastrulation Dalcq {1938) recognizes an /ctoblasi which later splits into neural plate (neuroblast) and epiblast a chotda mesoblast soon separating into notochord and the mesoblast which forms the somites nephrotomes coclomic linings and mcsenchjTne and anfnJoMojt which gives origin to the epithelial hiungsof the digestive and rcspirator> tracts


Individuals of a species show manv vanaiions vvhich arc the result of genetic inequalities random alterations in the environment dunng development or both B> averaging these intraspecific variations it is possible to define an abstract norm to vihich the majont> of individuals of the species approximate Fhosc individuals within close range of the norm are considered to have undergone normal development (normogeneru) Those individuals outsiae this more or less arbitrarj range are considered to have undergone abnormal development [ieratogenesu) and if their final state shows an abnormalit) of form the> are said to be malformed Abnormalities of function ma> also result from genetic factors (c g haemophilia and mbom errors of metabolism) the> ma) be associated with malformations and frequenth cause morphological changes

The causes of abnormal dev elopment arc either hcrcditar> env ironmcntal or combinations of these The evidence m support of the inherited nature of man> abnormalities is over whelming (sec Gates 1946) and in lower ammals it has been found possible to link certain abnormalities with specific chromosomes and even m certain instances with alterations in particular genes But v\hilc the hercdifar> nature of man> abnormalities is full} established there is convincing evidence from experiments on animals and it vvould seem even from data on human development that malformations can be produced b} adverse environmental factors It is obvious that m viviparous vertebrates and especiall} in mammals the developing organism sequestered m the maternal bod> is not readd} subjected either accidentally or expenmentally to the effect of environmental changes Even under these conditions however the maternal body is not a complete protecuon for the embryo but the action of certain possible adverse factors is much reduced Thus there is a marked diminution m the nsk of mechanical damage ovMng to the protective influences of the uterus and the membranes with their con tamed fluids There is much evidence however to show that the placenta docs not form a completely impermeable barrier to the passage of substances (e g , toxins and infectious agents) that can act adversely on development Further, the absence or marked diminution in the supply of V itamins trace elements or certain ammo acids can dramaticallv affect the general

abnormal development is considered m a general manner delads of developmental anomalies are referred to in relauon to the descriptive embooI<^ of the different organ ivstems The li?™ature ?. .t d';; elopment is extensive but a, Needham (,94s) has staled for that pari of it devoted to teratomat"

itis marked b> an unusual degree of unscienufie sprcuUuon inaccurate desenpuon and loncal mistakes ■pie be i sunev ofthe subject from the desenpme VTevrpoint is Sch albes Mor^hologie der Mi«b^u^«n (1907 it uq ) which should be consulted before considering an) parucular anomal) as raw or worthy of record



growth of the embryo In certain instances, indeed (see Boyd and Hamilton, 1950, for review), such deficiencies can cause more or less specific abnormalities of development.

The abnormalities of development that can be attributed to genetic causes may be in the nature of mutations, but they frequently result from the action of genes (dominant or homozygous recessive) which operate adversely on some process of development. The resulting abnormality is due partly to interference with this particular process and partly to the attempts of other embryonic processes to compensate for the deficiency. The exact role of the genes in normal or abnormal development has not yet been established, but it is generally considered that they act by elaborating chemical substances affecting differentiation and, in particular, the rate of developmental change In normal development the differentiating processes proceed at a definite speed and different processes are synchronized. “The genetic material controls the velocities of production and the time of action of the determining stuffs which control differentiation. The proper timing of the processes is the decisive feature in the general control of development” (Goldschmidt, 1940). If the timing of the processes is not synchronized, then abnormal development results Some genes (autonomous) exert their influence directly on the developing tissue m which they are situated, others (heteronomous) affect development of tissues remote from their immediate zone of activity, by modifying, for example, the function of an endoci me gland, the product of which has an influence on developing tissues (see Haldane, 1941, for discussion) It is possible to simulate genetic abnormalities by environmental alterations (e g , chemical and physical agencies) , the environmental alterations act as teratogenetic agents in the same mannei as abnormal genes, that is, by affecting a process, or processes, of development Such experimental simulations of genetically determined abnormalities are phenocopies (see Chapter I)


Normal differentiation of the organs of the embryo involves proper occurrence of the intrinsic and irreversible changes underlying the appearance of new strains of cells. It is also necessary that the activity of the whole hierarchy of organizers (primary, secondary, etc ) must be properly integrated, with each of them exerting its inductive effect in the right place, at the right time, and in the proper strength. Should an intrinsic tendency or an adequate inductive stimulus be absent (or if the substrate tissue is refractory to it) the primordium of an organ may fail to appear (agenesis, e g., absence of the lens of an eye, absence of an arm or a finger) (Fig. 390) Absence of an organ may also be due to its disappearance in subsequent development owing either to an inherent genetic deficiency in the tissue (Streeter, 1930) or to interference with its blood supply by some quite different developmental abnormality (e.g , absence of digits or of the lens in mice as the result of excessive production of cerebrospinal fluid which spreads subcutaneously and forms blebs which interfere with the blood supply and normal relations of the embryonic tissues, Bonnevie, 1934) Streeter has shown conclusively that such abnormalities as absence of digits or of a part of an extremity are not due to such occasionally alleged conditions as strangulation by amniotic bands or umbilical cord If the inductive stimulus is not adequate in strength, or if the substrate tissue does not give the normal response, the resulting organ will be smaller than normal (hypoplasia) and incompletely differentiated. When the inductive stimulus is for any reason separated, in space, into two or more components the organ concerned may be subdivided or reduplicated (supernumerary organs, e.g., h^qierdactylism, polymastia, double ureter and kidney). Some types of twinning, complete and incomplete, represent special and exaggerated examples of the results of subdivision of the inductive stimulus (see later in this chapter). If the inductive stimulus arises in an aberrant position or exerts its influence in an atypical direction the resulting organ, or organs, will occupy an abnormal (ectopic) position. Ectopic positions of organs may also resu t from irregularities in morphogenetic movements, anomahes in the positions of neighbouring organs, failure in differentiation of embryonic partitions (e g., the diaphragm), or hormona abnormalities (e.g., descent of the testis). If inductive stimuli, which are normally bilatera ,


should, for any reason become fused in the middle hne then a single median oi^an ma> result instead of the normal bilateral structure (c g the median eye of the cyclops Fig 341 uhich anscs as a result of failure in differentiation of the head mesenchyme from the prochordal plate 50 that the eye pnmordia and their orgamzer mechanisms become fused) Excessive inductive activity which may be due to the orgamzer itself or to an anomalv in the response (atyTiical competence) in the reacting tissue or the action of an organizer at the wrong time m development mav result in certain types of abnormalities of differentiation w hich require special com ment These are the so called teratomata which are tumours of developmental origin They mav be well differentiated histologically but usually show imperfect and frequently bizarre morphological differentiation and are embedded in the body of othcrvvisc normally developed organisms They are often regarded as examples of the assimilation of a twin into the bodv of the embryo but their characters make it much more likely that thev result from unco ordinated orgamzer actmty rather than from the separation into tv*o of a normal inductor system (see Needham 1942 for a discussion)

\bnormahtics of differentiation and of growth frequcntlv accompany each other Thus abnormalities of differentiation of the hmb skeleton will frequently be accompanied by gross changes in the limb proportions relative to the body as a whole (e g m that vanetv of dwarfism known as achondroplasia) Further abnormallv differentiated organs are frequently found m atypical positions because of the differential growth rates of related parts (e g non descent of the thyroid gland in cretinism}

\ large number of congenital anomabes cannot yet be interpreted in terms of inductor abnormalities Some of these can be explained as due to developmental arrest (eg non fusion of embryonic parts which result in such anomalies as hare lip and cleft palate) others can be attributed to widespread functional and structural abnormalities m all the derivatives of a particular germ layer (e g the so called mesodermal syndrome m which a great many mesodermal dcnvatives may be affected or the condition of epiloia m which widespread ectodermal deficiencies are associated with anomalies in the development of the nervous system) Gruneberg (1943) has dealt vvith a number of such complicated developmental anomalies in the mouse and has clearly shown that m many cases the final involved result can be traced back to a particular abnormality which is probablv due to a particular gene In man such conditions are known to be frequently hereditary but the genetic conditions under lying the transmission are complicated and cannot be expressed in simple Mendclian terms Fmalh attention must be draw-n to the fact that in the course of normal dev elopmeni there is evidence of the death of isolated or groups of cells (See Clucksmann 1951, for review ) How far this apparently normal death of embryome cells can become excessive and abnormal and contnbute to developmental abnormality has still to be determined


The embryo or foetus inutero can become infected by certain bacteria or viruses responsible lor acti\c disease in the mother The embryo can also show mamfestations of disease as the result of maternal nutritional deficienaes Consequent on the disease processes due to either of these environmental conditions the child may show abnormalities of development Con versely n may show disease changes resulting from abnormalities of development If a diseased

octus In cs until full term and is deliv cred with the disease processes still activ e it is said to suffer irom congenital disease This term however, is often used loosely to include abnormalities •^pasture (1942) considers that intrauterine infecuon is the result of spread of disease from ^ susceptible and infected mother to her foetus Rarely if ever docs a mother immune to a parucular disease permit the passage of infection through the placenta to the foetus Futhcr wore even in a susceptible mother the bacterial virus or protozoal infection must be blood wnie if the foetus is to be attacked this is probably why poliomyelitis so common in pregnant women docs not infect the foetus Actually a mother passivelv immunizes the foetus in utao



there is considerable confusion in its precise application (Hamlett and Wislocki, 1934) Twinning in mammals may be classified as follows —

1. Twinning in species which ordinarily discharge only one ovum {monovulatory species), e g , most primates and most large ungulates This twmmng may be either monozygotic or dizygotic. In the former, two (or, rarely, more, e g., triplets and quadruplets) embryos result from the fertilization of a single ovum by a single sperm In dizygotic twinning there is the discharge and fertilization of two (or more, polyzygotic) ova in a single ovulatory cycle Combinations of monozygotic and dizygotic twinning are known in cases of triplets or higher multiple piegnancies m women In monozygotic twinning the twins are “true,” like or identical and as they have the same genetic structure they are of the same sex and are essentially similar in structure and appearance. In dizygotic twinning the twins have different genetic structures and may be of the same or different sex. They are “unlike” twins, 1 e , they may bear no greater resemblance to each other than other members {siblings) of the same family which result from preceding or succeeding pregnancies. For this reason they are called “fraternal twins” Twinning in monovular species is usually sporadic and is regarded by some as an atavistic reversal to a more primitive condition.

2. “Twinning” in species which normally discharge two ova in each cycle {diovulatory species), e g , marmosets and the euphractine armadillos. Here the twins are fraternal and are, of course, the rule since two offspring are normally produced at a birth

3 The offspring of a single pregnancy in mammals which normally discharge more than two ova in each cycle (e g., polyovulatory species such as ca^rmvores, rodents, msectivores, some bats and a few ungulates) are comparable to fraternal twins, but are called litter mates. However, monozygotic twinning of single ova of such species is known to occur so there may be sets of identical twins among litter mates. As marsupials are also polyovulatory it would appear that polyovulation is a primitive feature of Eutheria and Metatheria.

Regularly in at least one mammalian group {dasypodine armadillos) and sporadically in many other species, including man, a fertilized ovum may give rise to four, or even eight, embr^'os (Patterson, 1913). This condition is known as polyembryony and the resulting embryos are “identical ” Polyembryony must be distinguished from the condition found in polyovulatory species. In polyembryony the embryos possess separate ammotic sacs but are enclosed within a common chorion. In autonomous fitter mates each embryo normally possesses a separate chorion, but occasionally the chorions may fuse, giving rise to the condition of sjmchorial litter mates.

Fig 1 1 7 — A scheme showing the relationships of the membranes and the interrelationships of the foetal and placental circulation in A — identical twins, B — fraternal twins


  • 3 *

TWINNING AND MULTIPLE BIRTHS IN MAN Human twins are of two types, monozjgotic ( identical or like tw^ns) and dizygotic ( unlike or fraternal twins) The condiUon is frequent (about i in 90 births) and about one quarter of all human twins are monozygotic

The immediate cause of dizygotic twinning is obviously the shedding of two o\a at approxi mately the same time in one ovarian cycle In most cases these ova are derived from two separate ovarian follicles but the occasional presence of two ova in a single unruptured follicle suggests that some cases of dizvgotic twins arise by rupture of such a follicle There is evidence that multiple ovulation and therefore dizygotic tvvinmng is a hereditary character Fraternal twins are usually dichonal (Fig 117B) but may show synchon&l fusion

The immediate cause of monozygotic twinning which also appears to be hereditary is either a separation of the formative embryonic material of a single fertilized ovum into two masses, each of which undergoes separate development into a complete embryo or the separate establishment of tw o (irgmi<.xng ctrOrei in a single formative area If separation is incomplete or if the ‘organizing centres overlap m their influence then the various forms of united twin monsters of the Siamese variety result (Fig 118) The precise time of partitioning of the

Fic iiS — Equal conjoined twins A — donal union (craniopasus) B — ^vemral union (cephalo»thoraeopagus or ;anicep$) C — ventral union (tnoraeopagus) D— dorsal union (pygopagus)

formative material in the production of monozygotic human twins is unknown It may, as some believe occur at the two cell stage in which case the resulting embryos may have com pletcly separate chorionic sacs and placentae (Curtius i9'’8) or it may occur, as is more likely in most cases at a later stage with separation of the inner tell mass into two and the subsequent retention of the embryos in a single chorionic sac (Fig 117A) or even in a common ammon The separation of the inner cell mass into two results in the establishment of two primitive streaks and therefore in the laying down of two embryonic axes After the time of establishment of a single primitive streak in normal development it is unlikely that twinning can occur as the changes accompanying lU formation result in the determination of the bilateral symmetry of the embryonic disc and thus in the establishment of a single embryo

If in monozygotic twinmng the separation into two parts is grossly unequal or if one component is more fortunately situated so that it monopolizes the placental blood then the smaller mass may become a parasite on its twm host (autosile) or it may die

As monozygotic twinmng results in two individuals with identical genetic backgrounds a study of the mental and physical characteristics of such twins is extremely valuable m any attempt to determine the relative effects of heredity and environment in the production of the mature individual There is an extensive hterature on this aspect of twinmng which has been summarized by Newman et al (1937) and Gates (1946) Langes book ( Crime and



Destiny,” 1930) is a significant contribution to the sociological implications of the investigation of twins. Of special interest are the cases where, for some reason or other, monozygotic twins have been separated early in life and brought up apart. The analyses of such cases show that their structural resemblances remain much the same as when they are brought up together and, on the whole, so far as their psychological resemblances and differences are concerned, heredity appears to be more potent than environment.

In about 25 per cent of identical twins the phenomenon of lateral inversion (mirior-imagmg) is shown. The degree of mirror-imagmg is variable and finds its more usual expression in such things as handedness, hair whorls, dental anomalies and finger prints In extreme cases m one of the pair of twins the asymmetrical organs of the body are on the usual side, whereas in its co-twin they are on the opposite side (situs inversus viscerum). This condition may be complete or partial, and it is frequently associated with other developmental anomalies

Higher degrees of human multiple birth than twinning are much less common, but triplets and quadruplets may result from multiple ovulation or from polyembryony of the type shown by the dasypodine armadillos. The Dionne quintuplets probably arose in the following fashion the initial formative material separated to give twins, then each of these divided again giving two sets of twins (quadruplets) and a final division of one of the quadruplets gave the fifth embryo, thus the “quins” resulted from “incomplete triple one-egg twinning” (Newman, 1940)

Siamese Twins and Duplex Monsters. Double monsters (or terata) are merely more or less incompletely separated monozygotic twins Such monstrosities may be almost completely separated (Siamese twins) or one component may be so reduced that it appears only as an appendage of its co-twin If the reduced twin is completelv embedded within its co-twin it may form one variety of so-called teratomata.

Double monsters can be classified according to the nature and degree of the union As they constitute a continuous series of stages between a single individual and completely separated monozygotic twins any classification of them is arbitrary. Terms frequently used in describing equal, conjoined twins (Fig. 118) are thoracopagus (symmetrically developed individuals united in the thoracic region), xiphopagus (united in the umbilical region), pygopagus (umted m the sacral region), craniopagus (united by the head) Unequal conjoined twins may show the parasite attached as a small, more or less fully formed foetus or only a partial foetus attached to almost any conceivable part of the head or trunk Fortunately, owing to difficulties at parturition, most conjoined monsters do not survive. There are cases, however, where the fusion is slight and surgical intervention results in two surviving individuals

Experimental Twinning. In many invertebrates and lower vertebrates it is possible experimentally to produce twinning and double embryos of the fused monster variety Thus twins or double monsters can be obtained by partial or complete separation of the first two blastomeres, each of which develops, or attempts to develop, into a complete though small embryo. Such results are obtained only in those species m which that part of the cytoplasm of the ovum which is destined in normal development to give rise to the mesodermal derivatives is included in each blastomere at the time of the first cleavage division As the future primary organizer is associated with the early mesodermal cells, it can be concluded that in most cases of duplication of development two embryonic axes are established by separate orgamzing centres. In some ammals (certain Annelids, eg , Nereis, and the mollusc, Cumingia), in ee , only one of the first two blastomeres receives the mesodermogenic material, and when t are separated it is this blastomere alone which will give rise to an embryo. It is also pOTsi e to produce twrinning or double embryos by physical (e g , temperature changes an ra lations; and chemical (e g., magnesium chloride or insufficient oxygen) agents. Here t e ou mg is due to some action of these agents on the mechanism of gastrulation and organizer pro uc ion, which results in the establishment of two or more embryonic axes, which may e comp e e y free or partially fused. Similar results are obtained by grafting the organizer region rom one developing embiy'o into another embryo, or by implanting tissues or substances w ic mi 1



the organizer nction Nicholas and Hall (1942) hase reported the e^pcriincntal production of twin embr>os from separated blastomercs m the rat but these embrjos did not proceed far in dcsclopmcnt


M N and Rh their occurrence

Bland P B dOiO Influenza m Us relation to pre^nc> and labour Imrr J Obit 79 1C4-197 Bonneue K (t934J Embr>ological an3l>-sis of gene inamfesution in Liiile and Baggs abnormal moutc tribe 7 Up ^oo! 67 443-5 “ ^ .

Boorman K L and Dodd B L ( 1943 ) Group-specific substances V

in ti sues and bodv fluids J Pat't end Batt 55 33<^-339 , , , ~ .

Bo'd J D and Hamilton \N J (i9aO) \bnorinal deselopment and foetal death /n Modem Trends lO Obstetrics and CmaecolotOi (Bo' es) Duuert»orth London Burke Bertha S Bea! \ \ Kirkt ood S B and Stuart H C (1943) Nutrition studies dorm? pregnane)

dTTter J Obit C» te 46 38-5

Child C M (tO)!' 1 atterns and I roWems of Development Unu Chicago I teas Chicago

Curtius F 1928) Uber erbliche Reziehungen zwisrhen aneiigen und zwciengen ZwiHingen und diC Zi illmgsvererhung im allgemeinen J Aawriforujiu/rAre 13 j8G-3I7

Dalcq k M ^19381 horm and Causalitv in Latl) Development Cambridge Univ Press London Driesch H (iBnn Entv,icklungsm«ehan»sche bludien t Der tSerih dcr lieiden ersten furchungszellen m der Echinodermentviicklung ETperimcnielle FrzeugungtonTheil und Doppelbildungen 2 Uber die Beziehungen des Lichtes zur enten Liappe der thienschen Formbildung Z^ils f uus ^oe/ 53 ■ 60-184

Evans H M and Bishop K S (19J3) The production of sirrilil) with nutritional regimes adequate for growth and us cure i iih other loo^iufTs J \ttleb Bft 3 233-31G Gates R R (19461 Human Genetics Macmillan Net \otlc

Glatihaar E and Tondurv G (t9jO) Untenuchongen an aborttern Fruchten nach Rubeolaerkrankung der Mutter tn der Fruhschwangerschaft Cfnafteloi'ia 129 313-320 Clucksmann \ (1931) Cell deaths in normal vertebrate oniogen) Oiel Btc 26 59-8C Goldschmidt R (19401 The Material Basts of Evolution \alc Univ Press New Haven Goodpasture E \N (19421 \ irui infection of mammalian foetus Seuiur 95 331-39^

and \ndrnon K. (iqi") \irus infection of human foetal membrane grafted on chorio>allantois of chick

embrvos im ] Path 18 563-575

Gregg N H (19411 Congenital cataract follovving German meavles m mother Tr Ophth Sue iustralia 3 35-46

Gruneberg H (1943; Genetics of the Mouse Cambridge Univ Press London Haldane J B S (^ 4 U New Paths m Genetics Mien 5 . Unwin London

tlale F (1935) Ine relation of vitamin \ to anophthalmos m pigs Imrr J Ophth 18 10G7-109

(19371 The relation of maternal vitamin A deficiency to microphthalmia in pigs Ttxet StaU J \Ud

33 2 8-232

Hamlett G and Mislocki G B I1931I Proposed classification for i)pes of n ins in mammals iital Rtc 61 81-96

Lange J (1930) Crime and Destiny Bom Nesv 5 ork

Le me P (1943^ Serological factors as possible cause in spontaneous abortions J HttedtH 54 71-80 — — ( 1944 ’ Iso immunization bv Rh factors of red blood cells A ck Path 37 83-90 McCrady E Jr (1944; The evolution and significance of the germ layers J Ttnn And Sci 19 240-251 Mason K E (19391 Relation of the vitamins to the sex glands /n Sex and Internal Secretions (Allen} Bailliere London

Medav ar P B (19471 Cellular inheritance and transformation Dial Pn 22 360-389 Mollison P L (lOjo) The Rhesus factor in pregnancy fi Modem Trends m Obstetrics and Gynaecology (Bov es; Uutterwonh London

— — Mourant A E and Race R R (1948) The Rh blood groups and their clinical effects M R C Memorandum No 19 H M Stationery Office London Murphy D P (1947) Congenital Malformations a Study of Parental Characteristics Lippincott London Needham j (193!; Order and Life Cambndge Univ Press London (1942 B ochemiitry and Morphogenesis Cambridge Univ Press London

Waddington C H and ^cedham D M (1931) PhvsKxxhemical experiments on the amphibian

organizer Proc Roy See Land BIH 393-4 2

Nc' man H H (19401 Multiple Human Births Twins Triplets Quadruplets and Quiniupleis Doubledav Doran &. Co Nev \ork ’

Freeman F N and Holzinger K J (1937) Twins a Study of Heredity and Environment Untv

Chicago Press Chicago

Nicholas J S and Hall B \ (1942; Expenmenu on developing rats II The development of isolated blastomcres and fused eggs J Exp 90 441-458

Noback C R and kuppertnan H S (1944) Anomalous offspring and growth of Wisiar rats maintained on a deficient diet Proe Soe Exprr Bio} \Ud 57 183-18^

Oppenheimer J M (1940) The non specificity of the germ layers Q art Re Biol 15 i-'>7 Patterson J 1 (1913) Polyembryonic development in TuftoKi jiatemfinrfa 7 Morph 24 xco-66 Pickles M M (19491 Haemolytic disease of the newborn Blackv ell Oxford ^




Roux, W (1888). Beitrage zur Entwicklungsmechanik des Embryo Arch J Path Anat u Phys [Virchow's],


Schwalbe, E. (1907) Morphologic des Missbildungen der Menschen und der Tiere Die Doppelbildungen Fischer, Jena

Spemann, H (1931) Uber den Anted von Implantat und Wirkskeim an der Orientierung und Beschaffenheit der induzierten Embryonalanlage Arch f Ent [Roux'), 123 , 389-517

(1938) Embryonic Development and Induction Yale Umv Press, New Haven

and Mangold, H (1924) Uber Induktion von embryonalanlagendurch Implantation artfremderOrgamsa toren Arch f Ent [Roux'), 100 , 599-638

Fischer, F G, and Wehmeier, E (1933) Fortgesetzte Versuche zur Analyse der Induktionsmittel

Naturw , 21, 505-506

Streeter, G L (1930) Focal deficiencies in foetal tissue and their relation to intra-uterine amputation Conlrib Embry ol , Carnegie Inst Wash , 22 , 1-44

Swan, C, Tostevin, A L, and Black, G H B (1947) Final observations on congenital defects in infants following infectious diseases during pregnancy, with special reference to Rubella Med J Austr , 2 , 889-936

U rner, J A (1931) The mtra-uterme changes in the pregnant albino rat [Mils norvegtcus) depri\ ed of vitamin E Anat Rec , 50 , 175-187

Waddington, G H (1932) Experiments on the development of chick and duck embryos cultivated in vitro Phil Trans Roy Soc , Land , B 221 , 1 79-230

Warkany, J (1944) Congenital malformations induced by maternal nutritional deficiencv J Pediat , 25 , 476-480

and Nelson, R G (1942) Skeletal abnormalities induced in rats by maternal nutritional deficiency

Arch Path , 34 , 375-384

Nelson, R C , and Schraffenberger, E (1943) Congenital malformations induced m rats by maternal

nutritional deficiency Amer J Dis Child , 65 , 882-894

and Schraffenberger, E (1946) Congenital malformations induced m rats by maternal vitamin A

deficiency Arch Ophth , 35 , 150-169 Weiss, P. (1939) Principles of Development Holt, New York ■ (1950) Perspectives in the field of morphogenesis Quart Rev Biol , 25 , 177-198



No organism suth as high a metabolic rate as that of \ertcbrates can grou be>ond a \olume of more than a few cubic millimetres without developing a functional circulatory s>stem This IS the result of physical limitations of simple diffusion in supplying the requisite respiratory, nutritional and excretory exchanges between the interior of the tissue mass and its surface It IS not surprising then th at the cardio vascular system is the first organ system of an embryo to reac h a functional state_ I he primor^ia of certain systems for example the neural plate appear at least as early ^ the blood vascular elements but the latter develop so rapidly that they become functional while the others are still relatively undifferentiated Hence well difierentiated vascular elements are found in early embryos and are intimately associated with the very early pnmordium of each organ Furthermore, since the circulatory system must service every part of the embryo at all times it undergoes rapid and extreme alterations of pattern in adjustment to the changing forms of the growing and differentiating complex of organ systems which is the embryo

In the human embryo the circulation of the blood has almost certam b-Jtarted _bv_the beginning of the ^th week, that is by the 7 somite stage (figs 97 and 143) At this time the blastocyst is about i cm m diameter, but the distance of the embryonic body from the nearest maternal blood in the early placental blood sinuses is probably not more than 3 mm This however is too great a distance to be served adequately by direct diffusion

It should be realized that the embryonic body at this time and for the next three or four months is very small compared to the mass of placental chorion through which the embryonic blood circulates Hence in order to furnish the necessary propulsive power and channels sufficiently large 10 carry adequately the blood to the extensive extra embryonic circulation the heart and the intra embryonic vessels must be many times larger relative to the embryonic body than are the adult heart and vessels to the adult body This discrepancy m size between the extra embryonic and the mtra embryonic circulations begins to decrease rapidly after the 5tVi month in association with the greater absolute increment of foetal growth However, only at birth is the foetal heart relieved of the burden of the extra embryonic circulation a circum stance to which the heart adapts by a neonatal size adjustment particularly of the right v cntricle


The origin of the endothelial lining of the heart and blood vessels must be briefly con sidered before proceeding to the description of the development of these structures In vertc brates generally endothelial tissue first appears in relation to the yolk sac wall as isolated cellular cords which later develop a limien (Confluence of the lumma of separate cords results m the formation of an cndotheliaTnet work of vi telline vessels By extension and growth this network progressively approaches antfTs eventually found within the embryonic body Primitive blood cells are found within the endothelial Lning of the network but the histogenetic relation between the endothelial and blood cells is not yet adequately established It is generally accepted that the endothelial cells lining the vitellme vessels are oT splancfinopleunc mesodermal origin (Evans 1912) Mmot (igta) however considered that this endothelium arises from yolkjeUs lying between the endoderm and mesoderm Reagan (1917) furnished evidence to support the conclusion that the vitelline prevascular tissue can originate from either mesoderm

or ^endode rm

Not only are there these different opinions concerning the ongm of the extra embryonic endo ihelium but there are also two conflicting ideas on the relationship between the endothelium,

  • 35



lining the vitelline vessels, and that which is later found within the body of the embryo .

(i) The view that the extra-embryonic endothelium extends into the embryonic body and permeates Its tissues to give origin to the whole of the endothelium of the embryomc haemo-lymph system This is the so-called angioblastic theory of His (igoo), which has as its essential feature the conception that all the intra- and extra-embryonic endothelium develops from a common mass

of precociously segregated angio


blastic tissue. (2) The view that the intra-embr yonic endo thelium differentiates in situ from m^em brvon ic mesoderm ^nd only secondarily becomes united with the extra-embryonic vitelline network This is the theory of “local” origin which has as its essential feature the conception that mesenchyme in any situation can become transformed into endothelium if the environmental conditions are suitable This latter view is supported by most investigators and appears to be confirmed by much experimental work Lewis (1931), however, has shown, by the cinematographic study of the growth of vascular tissues in vitro, that small portions of endothelium may become separated from the parent tissue and give the appearance, in later growth, of independent origin from the mesenchyme

In the placental mammals the problem of the origin of the endothelium is further complicated by the presence of active blood vessel formation in the chorionic mesoderm Hertig (1935) states that, in the macaque and human chorions, endothelium and primary mesoderm are simultaneously differentiated from the trophoblast prior to the formation of vessels in the yolk sac wall Such an origin for the primary mesoderm, however (page 73), is not generally accepted, and M’Intyre (1926) and others con

Fig 119 — The doi^al aspect of a model of a late presomite human embrj'O m tshich the ectoderm and the somatopleunc mesoderm covering the mtra-embry’onic coelom have been remo\ ed to show “angiogcnetic tissue” l>mg m the splanchnopleuric mesoderm A — communication between intra- and e\tra-embr}onic coeloms (Modified from Da\ IS, 1927) x c 62.

sider that vessels in the connecting stalk, yolk sac and chorion arise about the same time and later become linked by extension of all three systems. Hertig, working



oa much more extensive material is quite explicit houevcr that the primitive >olk sac IS srcotidanly vascularized either from the chorion b> vva> of the connecting stalk or b> inward migration of primary mesoderm to the yolk sac wall \\hate\er the origin of the extra embryomc endothelium in the human subject may be, most embryologists believe that the mtra embryonic endothelium arises tn sHu from the mcsenthvme


The tissue from which the primordium of the heart develops first appears in the late presomite embryo as separate scaiicred small cndoibclial masses which arise m the mesenchyme of the anterior margin of the embryonic disc in front of the neural plate {Fig 119; This (ardagemc area v\ hich is closely related to the anterior, pericardial portion of the coelom (page 53),

Fio 120 — \ drav>ing of a setlion through the detehptng heart region of a 7 somue human embne. (alter Pa^ne 19'*5> Jt c >30 This section w at level \-Il m Fig 162

extends across the midhne and is separated posteriorly from the neural plate region by the area of the future bucco pharyngeal membrane (fig Rja) These endothelial masses he between the roesoihelial lining of the early pericardial cavitv and the endoderm of the yolk sac i e in the splanchnopleure The isolated groups of/cndothelial cells extend towards one another and fuse m such a manner that they form very short right and left endocardial heart tubes'^ach of which 15 connected ccphalicully with xn endothelial tube representing the corresponding first aortic arch and dorsal aorta and caudaJIy with a similar tube representing the corresponding fused vitelline and umbilical veins (Fig 124) ^

Branches of each dorsal aorta are soon connected to the corresponding viteUme vein by way of the primitive vascular network on the yolk sac ^nd to the corresponding umbilical vein through the vessels that form m the placental vilh There are of course, extensive com munications between the vessels of the vitelline network and also between those of the villi



floor plate optic sulcus













And, indeed, the two systems soon become connected with each other in relation to 'the body stalk. Nevertheless the pattern of an essentially bilaterally symmetrical arterio-venous system persists for several days The two endocardial heart tubes, however, soon fuse so that a duplex vascular system is transitory.

At about the time of first fusion of the two endocardial tubes primitive muscle cells, myoblasts,

differentiate from the surrounding splanchmc mesoderm and ensheath the endocardial heart. This myocardium IS rather widely separated, at least in microscopic sections, from the endocardium, but is intimately fused to the related splanchnic, or visceral mesothelium {epicardtum or visceral pericardium) (Figs. 120-123). These two layers are often referred to as the .JUNCTION OF FOREGUT myo-eDicardial mantle In


lower mammals and the chick the first functional heart beats are known to begin at about this time, although the myocardial cells do not yet show the peculiar cytological characteristics of cardiac muscle With the development of the head fold, the pericardial cavity and the fusing endothelial tubes undergo a rotation on a transverse axis through almost 180° so that they come to he ventral to the foregut and caudal to the buccopharyngeal membrane (Fig 84) , the septum transversum (.page-55) comes to he between the pericardial cavity and the yolk sac (Figs 121 and i 44 )' The endothelial heart tubes, clothed by the myo-epicardial mantle but separated from It by a loose reticulum, are now situated in a definite pericardial cavity (Figs 120 and 162). Each endothelial heart tube is connected, at its caudal extremity, ^vith the dilated termination of the corresponding vitelline vein from the yolk sac. This dilatation is joined by the corresponding umbilical vein to form the right or left primitive sinus venosus (Figs. 77, 126, 127 and 144), which later receives the termination of the duct of Cuvier (common cardinal vein or truncus transversus of Reagan) of the same side (Fig. 145)- Each duct








Fig 121 — A drawing of a median section of a reconstruction of a 10somite human embryo (after Corner, 1929) x c 48 The endothelial heart tube is coloured red


of Cm ler is formed In the union

ofthccorrespondinc'fln/rnonnd posterior earJmal reins which ^^c dmnin:; the cmbrsonic bod\ wall

The cephihe end of each heart tube extends beyond the region of the pericardial casilN where it is continuous on each side with a plcxiform sessci which has difTcrcntiated »n situ in the mesoderm of the first branchial arch This \es el passesdorsallj roundlheprimi Use pharanx as tlie first oorlie areh artery and is continuous with tlie corresponding dorsal aorta (Figs 77 12} and which is also differ

entiatinginri/uin the mesoderm (lankim, the side of the noio chord (Fif^s 120 122 and 123;

The fusion of the endothelial tubes progresses from the cephalic to the caudal end to form a single endothelial heart tube The ni>o epicardial mantle now develops into the muscle (mvocardium) and the fibrous tissue of the heart wall and Its covering (the visceral pencardium) while the endothelial tube becomes the endo cardium For a short lime the endothelial tube and its mvo epicardial mantle are slung from the dorsal pericardial v»a11 b> a double mesothciial or serousfold thcmrroriiri/ii/m (Fig 120) Bv the ten somite stage (Figs 121 and 122) this meso cardium has become fenes trated and b> the sixteen somite stage has disappeared entirely Icavmga passage later the transierse sinus of the peri cardium from one side of the pericardial cavity to the other dorsal to the heart The endo thclial tube together with the myo epicardial mantle may now be called the cardiac tube



endoderm or























Fig 124 — The ventral view of a reconstruction of the heart region in a 4-somite human embryo (after Davis, 1927) X c 92 The arrow points into the anterior intestinal portal which leads to the foregut The endothelial heart tube is indicated by interrupted lines in this figure and in Figs 125 and 126





















Fig 125 — A \ie\v similar to Fig 124 of a 6-soniite human cmbr>o (after Da\is, 1927) x c 75

or primitive heait and can be referred to as the “single tube stage” of the heart. The primitive heart passes caudo-cranially through the pericardial cavity and, after the disappearance of the mesocardium, is fixed to the pericardial wall only at the venous entrance, or caudal end, and arterial outlet, or cranial end, trhere the epicardium is continuous with the parietal pericardium (Fig. 84C). The cardiac tube now undergoes differential expansion so that several dilatations, separated by grooves or sulci, are formed. These dilatations are, from the caudal to the cranial ends, the right and left sinus venosus, the right and leh primitive atrium (which later fuse to form a single atrium), the atrio-ventricular canal, the ventncle and the bulbus cordis (Davis, 1927, and Figs. 124127) The right and left sinus venosus and the atria are for some time embedded m the loose mesenchyme of the septum transversum. That part of the cardiac tube w hich becomes freed from the dorsal pericardial wall grows more rapidly than the pericardial cavity, doubling its length between the seven- and twenty-somite stages. As the venous and arterial ends are relatively fixed by the pericardium the tube becomes bent first in a rather U-shaped loop, which has its convexity directed forward and to the right, and shortly after > into a compound Sr^haped curve (Fig 126). It now nearly fills the pericardial cavity (cf Figs 122 and 123). As the loop involves mainly the ventricle and the bulbus it is called the bulbo-ventncular loop. The concavity of the loop deepens to form the left bulbo-ventncular sulcus (Fig 126). The caudal part of the cardiac tube now undergoes further differentiation.



the fusion of the primitive atrii giving rise to a single transversely dilated atrium which gradually becomes freed from the septum transversum and comes to lie m the pericardial cavity dorsal to and partly to the left of the hulbo ventncular loop (Fig 127) \

continuation of this separation process results m the almost com plete freeing of the right and left sinus venosus from the septum transversum so that they come to be situated on the posterior aspect of the atrium (Figs 129 1 30 and 13-3^ Here they undergo partial fusion to form a single sinus which opens by a single jmu atnal onfee into the atnal cavaty Thus at about the 5-6 mm stage the heart primordium is a single tube except for the most caudal part \v here por ttons of the venous sinuses remain unfused as the right and left horns of the definitive sinus venosus A. deep sulcus develops between the left sinus horn and the left aspect of the single atrium and at the same time this horn becomes much re duced in size owing to a rearrange ment of the vessels entering the sinus w hich results in the establish ment of a new venous channel the ductus lenosus (in the liver page 164) a shunt which brings most of the blood to the right sinus horn The right horn consequently cn larges and also becomes separated though to a lesser extent than the left from the posterior atrial wall The mam results of these growth processes are a change jn the position of the sinu atnal orifice to the nght side of the atnum and a conversion of the originally transversely onentated smu atnal onfice into a vertical one the margins of which project into the atrium as the ri^kt and left lenous lal es (Figs 130 133 and 137) WTiile these changes are pro gressing there is a gradual caudal

Fic 126 — \ view similar to Fig 124 of the heart ofa i&somite human embryo (afier Davis 1927) X c 75

Fio I ,—*^0 posterior view of the heart region in the human embryo (16-somiW) illustrated in Fig 16 x c 87



Fig 128 — The ventral aspect of the heart of a 5 mm. human embryo with the ventral pericardial wall removed

migration of the heait which brings it from the level of the third and fourth somites to a final position opposite the derivatives of the seventeenth to tiventieth somites This change in position together ivith the later development of the neck causes each duct of Cuvier to pass more and more obhquely to the corresponding horn of the sinus venosus and each vein raises an obhque pericardiopleural fold in the lateral wall of the pericardio-pleural opening These folds extend medially and eventually separate the pericardial cavity from the remainder of the coelom (page 2 1 8) After this closure the left duct of Cuvier becomes much 1 educed m size (see later, page 1 65) The atrium, ventricle and bulbus cordis now increase rapidly in size and at the same time



\ \ rjoge

N '














Fig 129 — The dorsal aspect of a reconstructjon of the heart of a lo mm human cmbr\o (after His, 1886) X c 38



undergo some rearrangement m position (cf Figs laG 128 and 132) atnum expands

trans\crseK and extensions from it appear on cither side of the cephalic (distal) part ofthebulbus

ss hith groo% es the cephalic aspect of the atnum The s entral extensions of the atnum become the auricular appendages in subsequent desclopment The left bulbo-\cntncular sulcus becomes reduced m depth and consequent!) the caudal (proximal) part of the bulbus is absorb^ into the sentricle sshich has now mo\ed towards the left and appears on the antenor surface of the de\eloping heart The atno \entricular grooics become accentuated dunng the changes so that a narrow waist the atno \entncular canal 1$ produced (Figs 127 and 129) The external form of the heart is now more or less established and «s subsequent histor> can best be desenbed b> considenng the changes in its intcnor


A coronal section of the heart at the 7 5 mm stage has the appearance seen in Fig 130 It IS e\ident that the cardiac tube is not >ct divided into right and left halves Tlie changes m the shape and position of the v arious parts ^ ^

of the cardiac tube described above how ever result in an orientation of the chambers which facilitates their subsequent subdivision The partitioning of the single cardiac tube is the major change undergone b> the develop ing heart and the commencement of the process is ahead) shown b) a heart m the stage of Fig 130 It must be stressed that while the heart septa are developing the heart must continue its aciivit) as a functional pumping mechanism Although the processes of septation are occurring simultaneous!) it IS an advantage to describe the partitioning of the various chambers separatel)


Vs a result of the changes ahead) described the opening of the definitive sinus venosus into the single atrium is brought to the right side Tlie atno vcntncular (A V) canal has also moved rclativcl) to the nght and IS now situated approximate!) in the middle of the atnal floor and hence Iicspostero superior to the common bulbo vcntncular cavit) TheA \ canal is at fint circular in section but itsoon becomes widened tranvcrsel) (Fig 132B) The onfice ofthe sinus venosus is bounded by the nght and left venous valves (Figs 130 and 133), which fuse supenorl) to form a maibed projection, the sepium jpmum m the roof of the nght side of the atnum Infcriorly they fuse to form a less vvell marked projection which can be found for a short time extending as far as the atno ventricular canal (Fig 130) In the region of the midlinc of the roof of the atnum w here it is groov cd b) the distal part ofthe bulbus a sickle shaped sagittal fold the septum pnmum appears at about the 5 mm stage to the left of the septum spurium from which it is separated by a small tntersepto lak-ular space To the left of this septum pnmum the onfice of the single pvdmotvac) vein is found* (Figs 129 and 130)

• "nie origin of ihe puImonar> vein j* uncertain Some authoriuev (Flini 190^) consider that it grows out trom the smiu venosus and establishes a connexion with the pulmonary venous plexuses others /e g Brovvn

  • 913; trinlc that 11 arises by the confluence of rudiments of the pulmonary plexus and secondanlv joins the sinus

venosus while >et others (Tandler igM Spiucr igai) hold that it ts connected primaril) with the left atnum II the pulmonaiy vein joins the sinus venosus it is difficult to explain its adult connexions unless v e postulate asdoes His (1B86) a contribution from the sinus venosus to the definitive left atnum For discussion see Davm and MacConaill (1937J

Fig 130 — A coronal section through a reconitruction ofthe hear: ofa 7 3 mm human embrvo (after His iBPfi) X c •'3 \=caudai fusion of the tnous valves The donal half of the model seen from the ventral aspect



As the septum pnmum grows caudally its anterior and posterior extremities extend along the corresponding walls of the atrium until they reach the elevations, the anterior and posterioi atriQ-ventncular endocardial cushions^ which have appeared in the anterior and posterior walls of the atrio-ventricular canal. The opening bounded by the free edge of the septum primum and the endocardial cushions is called the foramen pnmum, or primitive inter-atrial orifice, and this is soon obliterated by the union of the free edge of the septum pnmum with the fusing










3RD ventricle











LT A V canal






Fig 131 — A section at the level of the lung buds and developing heart region in an 8 mm human embryo X c 50

endocardial cushions. The primitive atrium is now divided into a right and left atrium. Before the complete obliteration of the foramen primum has occurred the cephalic portion 0 the septum primum undergoes degenerative changes which result in the formation, at t e 7 mm. stage, of a foramen secundum which brings the right and left atrial chambers into communication (Fig. 137). This is, of course, necessary so that blood from the right atrium enter the left as the latter receives directly only a limited amount of blood from the still very small pulmonary' veins.



Septum Secundum From the wall of the right atnum between the attachment of the left \enous vaKc and the site of ongin of the septum pnmum (i e in the ^11 of the mtersepto valvular space), a second septum, the septum secundum appears at about the i8 mni stage This septum anses as separate anterior and posterior portions (Odgers 1935) which eventually unite to form a single arched partition with a lower free concave edge which is at first directed v entrally and caudall^ , but soon as the result of grovN th inequalities comes to face caudall^ (Fig 134) and to have a postero inferior and an antero superior extremity Its low er edge ev entually ov erlaps the upper edge of the foramen secundum of the septum pnmum Postenorly the septum secundum fades out on the wall of the atnum to the left of the left v enous valve Its antenor extremity bifurcates one limb terminating in the left venous valve the other in a ridge the septum which appears m the wall of the sinus venosus between the part of the sinus which receives the tnjerm lena caia {nght iitelUne lein) and the portion receiving the coronary sinus (left horn of sinus lenosus)


Fio 133 — \ — The«entralaspcctoftbeh«artora tomm humanembrjo The ventral pericardial wall has been removed B— A coronal section through \ The dorsal half of the model is seen from the ventral aspect The antenor and posterior endocardial cushions situated between the right and lefc A \ openings have not > el fused

Foramen Oval* The growth of the septum secundum results m its free edge passing beyond the persisting lower margin of the foramen secundum The passage between the two atnal cavities is now an obliquely elongated cleft bounded by the upper edge of the penisting lower part of the septum pnmum and the lower edge of the septum secundum (Figs 135 and 137^) R called foramen oia'e and that part of the septum pnmum which bounds it, and overlaps from below and to the left the free edge of the septum secundum is called the cahe of the foramen orate In foetal life the foramen ovale permits the passage of oxvgenated blood from the infenor vena cava to the left atnum After birth owing to the increase in pressure m the left atnum the cephalic edge of the valve of the foramen ovale is pressed against the septum secundum so that eventually in normal development, the two atnal chambers arc completely separated from each other The depression which persists on the nght side of the inter atnal wall inside the arch of the free edge {annulus ocalts) of the septum secundum is called the fossa ov alls and it is separated from the left atnum by septum pnmum tissue




During the development of the inter-atnal septum, the right and left venous valves, which originally form distinct projections into the cavity of the primitive atrium and mark the sinuatrial junction, become much modified owing to the absorption of the sinus into the atrium. The left venous valve retrogresses, comes into contact with, and eventually fuses with, the posterior part of the mter-atrial septum m which region remnants of it may occasionally be found m the adult (Fig 135) The right venous valve is pushed ventrally and to the light

by the expanding sinus venosus, and



becomes divided into three distinct parts by the development of special muscular

















Fig 1 33 — A section at the leve of the developing heart in an 8 mm human embryo X c 50

limbic bands which extend, subendocardially, across the sinus as indicated in Fig 135. The superior limbic band crosses the posterior wall of the sinus venosus between the superior and inferior caval opemngs, and forms the basis of the socalled mtervenosus tubercle of Lower The inferior band is situated between the inferior caval orifice and that of the coronary sinus, and it forms the basis of the sinus septum The portion of the right venous valve above the superior limbic band together with the septum spurium forms the crista terminalis of the adult heart and, therefore, represents the line of junction of atrium proper and sinus The portion of valve between the two limbic bands persists as the valve of the inferior vena cava, whilst the part antero-mferior to the inferior limbic band forms the valve of the coronary sinus.



Just as the sinus is partially absorbed into the right atrium so, at first, the terminal portion of the originally single pulmonary vein, and then the right and left pulmonary veins to just beyond the junctions of their terminal tributaries, are absorbed into the wall of the left atrium. Hence four separate pulmonary venous opemngs, two right and two left, are usually found in the wall of the le t atrium


At about the time when the septum primum begins to grow down from the atrial roof two proliferations of tissue, the atrio-ventncular endocardial cushions (an antero-supenor ^ a postero-inferior), develop in the wall of the now transversely widened A.-V. canal ^ cushions, by their growth, meet and fuse at the 1 1 mm. stage and so divide the sing e • canal into right and left A.-V. canals (Figs. 132 and 138). The fusion occurs at approxima



the time \»hcn the free edge of the septum pnmum reaches and fuses %vtlh the upper sur face of the cushions the Imc of junction betuccn the septum and fused cushions (Fii, 137) being antero posterior and sUu atcd slightl) to the left of the midpoint of the cushions


From Its deselopmental histor> it will be seen that the right atrium is formed from three parts (t) the right Iialf of the primitne atrium (a) the sinus \cnosus and {3) the right half of the A canal Tlie pnmitisc atrial portion desel ops an appendage the auricle and shows mujfa/i pfelinati The walls of the sinus tenosus and atn il canal portions are smooth

The left atrium is formed from three parts (i) the left half of the primitive itnum (a) the dilated terminal por tions of the pulmonary veins (vestibular portion), and (3) the left half of the.^' canal The left half oTTfic primitive alnum forms pnn cipallj the left auricuhr appendage

SEPTATION OF VENTBICIE AND BULBUS CORDIS \t about the 7 mm stage shortly after the appearance of the septum pnmum an antero posterior muscular ridge ap pears m the floor of the bulbo ventricular cavity (Figs 130 and 131) It is at first due to the dilatation of each half of the bulbo ventricular cavity on cither side of and beyond a relatively fixed intermediate sagittal portion so that an antero posterior sulcus ippears on the surface With further

FiO «35 — \ disjection from the right s de of a foetal human heart to Utow the relationships of the limbiC bands and the fale of the val\es of the sinus \enosus



Fig 136 — A schematic di aw mg of a sagittal section through an embryonic heart to show the plane of the sections illustrated m Fig 137

active growth the posterior part of this inter-ventricular septum reaches the right extremity of the postero-inferior A -V eushion (Fig 132B) just to the left of the right A.-V, orifice (Fig 138) Theantenor part oftheinter-ventricular septum extends along the anterior wall and roof of the bulbo-ventricular cavity and eventually reaches the antero-superior A -V cushion somewhat to the right of the left A -V orifice The space bounded by the free edge of the inter-ventricular septum and the endocardial cushions is called the inter-ventncular foramen Through it, for a time, the right and left ventricular cavities, which result from the formation of the septum, are in free commumcation both with each other and with the cavity of the distal part of the bulbus In order to understand the further changes in this region it is important to note that the inter-ventncular septum is not precisely sagittal, but is orientated somewhat obliquely, especially in its upper part

Before the inter-ventncular septum has become established, at about the 5 mm. stage, spiral sub-endocardial thickenings, the bulbar ridges, appear in the distal part of the bulbus (Figs 133 142) In the proximal (1 e , juxta-cardiac) part of the bulbus the ridges are so

Fig 137 — Schematic sections to show the development of the mter-atrial and interventncular septa of the human heart Successive stages are shown from A to U In Fig. C, A represents the cranial remnant of the septum primum, B the caudal attachment of the septum secundum In I ig A represents the obliteration ol the intersepto-valvular space



situated that there is a n£,ht ndge projecting just abo\ e the right A V canal and a left one related to the anterior part of the inter aentricular septum (Fi 138) in the inter mediate pan of the hulhus the con tinuations of these ridges arc attached to the anterior and posterior si alb respectncl) and in the distal (ter minal) portion or Iruncui arttnosus the) arc attached to the lateral , walls B> the growth and fusion of the '» ridges at about the 20 mm stage a spiral aorlico pulmonarj is formed

which disides the bulbus cordis into the aorta and pulmonars arier) (Figs 138-142') and when the inter \entncular foramen is fmalls closed each of these arteries \\ ill be in com municalion with the corresponding ventricle

Cl OSURE OF THE INTER VENTRICULAR FORAMEN The inter v entricular foramen is closed b> tissue which proliferates from the lower parts of the right and left bulbar ridges and from the fused endocardial cushions The prohfera tion from the right bulbar ridge passes anterior to the right A V canal and fuses with the posterior edge of the inter ventneuhr septum (Figs 139 and 140) The prohfera tion from the left bulbar ridge fuses with the anterior edge and right side of the inter \ entricular septum The two extensions from the bulbar ndgcs then meet and fuse thus closing the upper and larger part of the inter ventricular foramen The closure of the remaining portion of the foramen (Odgers 1938 and Rramer 1942) is effected b) the prolifer ition of tissue from the endo cardial cushions which grows along the free edge ot the inter ventricular septum fusing with it and with the lower margin of the ahead) fused bulbar proliferations at about the 17 mm stage (Fig 140) The closure of the interventricular foramen

Fir 138 — \ model shoving ihe development of the imer ventricular septum and the bulbar riders in a IS mm human cmbr>o The pr >liferation» which eveniuall) result in the obliteration of the inter vrniricular foramen are coloured in this figure and in Fitts 130 and 140 \elIow {\ m Figs 13Q and ■ 30) represents the proliferation from the endocardial cushions Ted leptesents the ptolif laiion ftorn tl e Tight \ \i\bar ndge and bluerepres ntv the proliferation from the left bulbar ridge Figs 138 i3>)'and 140 are bavrd on descriptions b) Odgers (1938]

Flo 139— The inter ventricular septum and I ulbar ridges in a 14 5 mm human embr>o S e legend to Fig 138 The white arrow indicates the course of the blood'from the left ventncic to the aorta



results in the disappearance of the communication between the two ventricles and, at the same time, ensures that the right ventricular cavity is in communication with the anterior, oi pulmonary, portion of the bulbus and the left ventricular cavity ivith the posterior, or aortic, portion (Fig. 141). Further, the right A -V opening noiv commumcates exclusively with the right ventricular cavity and the left A -V. opening with the left ventricular cavity.

Pars Membranacea Septi. This IS a portion of the heart septum which remains throughout life as fibrous tissue. It IS situated partly between the right and left ventricles (i.e , in the upper part of the inter-ventncular septum) and partly between the left ventricle and right atrium (Fig 137D) The lower inter-ventricular portion arises from the atrio-ventricular endocardial proliferation which closes the lower portion of the inter-ventncular foramen The atrii^ventricular por


Fig 1 41 —A scheme to show the division of the bulbus cordis b\ the aortico-pulmonary septum The model

IS dissected and seen from its right side

tion of the pars membranacea septi owes Its origin to the fact that the septum primum and the mter-ventricular septum are not attached to the endocardial cushions directly opposite to each other As a result that part of the fused atrio-ventncular endocardial cushions between the attachment of the two septa lies between the right atrium and left ventricle At first the two parts of the membranous septum meets at a right-angle. Later the atrioventricular portion comes to he in the same plane as the inter-ventricular and mter-atrial septa (Fig 137).

THE CARDIAC VALVES Semilunar Valves of the Aorta and Pulmonary Aileries.

After the formation of the mam bulbar ridges which later fuse (see above) to give the aortico-pulmonary septum, two very short accessory ridges appear in the ventricular end of that part of the bulbus which becomes part of the truncus arteriosus. The accessory ridges alternate with the main ones


(Fig 142) \Shen the septum is formed by fusion of the main bulbar ridges, suellings of sub endothelial tissue appear on both sides of the ventricular end of each fused ridge similar to those produced from the ventncular ends of each accessory ndge Thus three stvellmgs guard the orifices of both the systemic and pulmonary aortae These ridges consist of a covering of endothelium over loose connective tissue These ndges arc soon exet^ted on their distal aspect to form the three cusps of the semilunar valves and it will be seen that their adult relations to each other are established by their embryonic positions

Atrvo Ventricular Valves These anse by proliferation of the connective tissue under the endocardium of the A V canals ancl partly from the fused endocardial cushions The proliferations are excavated on their ventricular sides but, owing to their proximity to the ventricular musculature they remain connected to the ventricular wall by muscular strands which form in part papillary niiuc/« and m part chordae Undineae The tntlral take develops two cusps only but the tricuspid lalie develops three According to Odgers (igSS) lower edge of the right mam bulbar ridge furnishes the basis for the anterior and right cusp of the tricuspid valve

Cardiac Muscle The mso epicardial mantle gives rise to the cardiac musculature the fibrous tissue of the heart and the visceral layer of the pericardium while the endothelial tube becomes the endo cardial lining

The cavities of the embryonic heart are at first smooth but the myocardium soon develops as a loose meshworl. the interstices of which are Imcd by endo cordium The walls of the heart cavities now consist of a spongework of muscular trabeculae the mlertrabecuhr spaces con stitutmg a considerable part of the capacity of more partjcuhrly the ventricular cavities (Fig 131 and 135) Later nn outer compact laver of myocardium is differentiated but the original trabeculae remain in part as the pectinate muscles of the right atnum the trabeculae of the auricular appendages and the trabeculae papillary muscles and chorda tendmeac of the ventricles For details of the histogenesis of the myocardial cells see Chapter \IV



The earliest mtra embryonic blood vessels form a diffuse plexus throughout the embryonic mesenchyme This stage of a diffuse plexus is followed by one in which separate plexuses are elaborated in relation to differentiating tissues and organs Larger channels are formed in the plexuses by the enlargement of individual capillaries and the fusion and confluence of adjacent ones while portions from which the flow has been diverted undergo retrogression and atrophy These processes result m the esubjishmenc of a circulatory mechanism which supplies the functional requirements of the newly formed and grovnng embryonic organs The factors controlling the selection and ditTcrcntiation of the appropriate channels in the plexuses and the elaboration of the structural charactensticx of their walls are not y et completely under stood It IS known however that genetic factors and local haemodynamic influences such as rate and direction of flow and pressure of the blood are both concerned m the establishment of the final pattern (Hughes 1943)

The earliest blood vessels are simple endothelial tubes the primitive arteries and veins cannot be distinguished structurally but can be named in arcordance with their future fates and their rehtionship to the developing heart In later development the mesenchymal cells

Fic 14 — Schrmaiic sfctions to shot successive stages in the subdivision ot (be bulbus (ordis and the development of (he cusps of the aortic and pulmonary semilunar valves



surrounding the persisting endothelial tubes of the primitive plexuses differentiate into the muscle and connective tissue cells of the tunica media and the tunica adventitia of the definitive arteries and veins. In accordance with the fundamental bilateral symmetry of the body the arteries and veins constitute initially a paired symmetrical system which, Iiowever, is much altered during development by the fusion, hypertrophy or atrophy of its various components.

Although the arteries and veins are closely linked in their development, the pattern of each system of blood vessels being dependent on the other, it is convenient to describe them separately.

It should be stressed, however, that the vascular system develops as a functional whole and that the isolation, for descriptive purposes, of the heart, arteries and veins is quite artificial


The primary embryonic arteries are the right and left primitive aortae They can be identified, in early somite embryos, as two vessels which appear as continuations of the two endocardial tubes (Fig 77A) Each of them passes from the region of the floor of the foregut, round the corresponding lateral side of the pharynx (Figs. 124, 125 and 145), to the dorso-lateral aspect of the gut (Figs 120, 122 and 123) along which it passes caudally as a large and, in the earlier stages, plexiform vessel (Fig 143), the dorsal aorta of the side concerned In its course each dorsal aorta gives off small branches to the intersegmental plexuses between the somites, vitelline branches to the corresponding side of the yolk sac and caudally a large umbilical branch , it then dwindles away on the dorsolateral aspect of the cloaca (Fig 144) Each primitive aorta can, therefore, be readily divided into three portions (i) a short, ventral, “ascending” portion; (2) a primitive (first) aortic or pharyngeal arch artery, lying in the mesoderm of the mandibular arch; and (3) a relatively long “descending” portion which distributes the blood from the heart to the embryomc tissues by the segmental plexuses and to the yolk sac and chorion by way of the vitelline and umbilical branches When the process of fusion of the endothelial cardiac tube reaches the anterior limit of the pericardial cavity it extends forward, beyond this level, to involve the caudal, or cardiac, extremities of the two ventral aortae. As a result the bulbus cordis is succeeded crania y, beyond the pericardium, by a single midline vessel called the truncus arteriosus or, since it becomes dilated in later stages, the aortic sac The right and left first aortic, or pharyngeal, arch arten«  arise from this relatively large chamber which is situated cramal to the pericardial cavity an in the floor of the pharynx (Figs 146 and 148) and the term “ventral aorta need no onger be used. The complicated adult arterial pattern is derived from this simple primor ° a truncus arteriosus, forming the arterial outlet from the heart, a pair of aortic arches, lying m e

Fig 143 — Dorsal aspect of a model of a 7-somite human embryo (after Payne) to show the early blood vessels The somites have been removed from the left side X c 50


mesoderm of the first pharjitgeol srehes and pantall) enctrclin? the phsrj ns and the paired dorsal aortae distributing the blood to the embrjontc body and to the \olh sac and chonon

PHAR'iNCEAL (DRANCIIIAL) ARCH ARTERIES With the caudal displacement of the heart and the formation of furtlicr plnr^nt^cal arches behind the mandiluloT pair, the first

pair of aortic arch arteries is supple mented b) the successive addition of five more pairs one m each of the arches (Figs 154 and 177)

These arteries arise ventraU> from the aortic sac and terminate dorsalI> m the dorsal aorta of the corresponding side In human development the SIX pairs of phar^mgeal arch arteries arc never all present at the same time The anicnor iv\o pairs in the mandibular and hold arches dis appear before the caudal two pairs in the 5ih and 6th phar> nqcal arches have differentiated Further the 5th pair of arches » never vveU developed and their arteries are onl> present for a vef> short time

Pliar>ngeal or visceral arches with their corresponding aortic arch arteries dev clop in all \ ertebrates In all the V ertebrates withjaws(Gnatho stomata } the first tw 0 pairs of phar> n geal arches become highl> modified to form the basic elements of tlie moutli and the middle ear (see page 343) Consequent!) the first and second pairs of phalangeal arch arteries arc not distributed to true gills In fishes (including selachians) and larval amphibians all the arches from the third pair caudalwords bear gills or branchiae and arc therefore called specificall) the branchial arches Their aortic arch arteries are the branchial arcli arteries During the period when there arc functional gills on

these arches each branchial arter) consists of an afferent portion carr) mg blood from the ventral aorta n> the capillaries of the gill filaments

Fig 144 — \ dissection of a model of a 14 som ic human embryo from the left side (modified from Heuscr) to s!io\ the earl) blood vessels x c G

and of an efferent arter> canning the ox>gcnatcd blood from the filaments to the corresponding dorsal aorta With the loss of the functional gills dunng metamorphosis of lung breathing amphibians and dunng earl) developmcntm reptiles birds and mammals the branchial arten«  undergo marked modification in the process of being altered into the pattern of the large arteries of the neck and thorax Their original arrangement and the steps in their development are



so essentially similar in all vertebrates that they form a particularly good example of the so-called Law of Recapitulation (Chapter XVI). In human development the phase of branchial arch arteries persists until about the 13 mm stage, but much later than this, and even in the adult, the basic branchial pattern can be recognized (Figs 152 and 188-190), The factors concerned in the modification of the branchial pattern in the higher vertebrates are principally (a) the establishment of pulmonary respiration, (/?) the increasing separation of the venous and arterial blood streams m the heart, and (c) the development of the neck with the associated retreat or “descent” of the heart.

Shortly after their appearance as separate paired vessels the dorsal aortae undergo two changes which have a considerable effect on the future development both of the aortae themselves and of the branchial arch pattern Firstly, each aorta grows cranially beyond the point






' /






v'-' ■ i

V. “





















Fig 145 — The left side of a model of the cranial part of the nervous system and of the heart and principal arteries and veins m a 22-somite human embryo (after Congdon) The arrow points into the pharynx

Fig 146 — ^Ventral view of the ist aortic arches and of the dorsal aortae in a 22-somite human embryo (after Congdon) The first arch is at its maximum development and the outgrowths, which are to aid m the formation of the second, are just appearing

at which the first pharyngeal arch artery joins it, and in close relation to the developing ram plate (Figs 125 and 145) These anterior extensions constitute the rudiments of the interna carotid arteries (Fig. 147) Secondly, the dorsal aortae fuse towards their caudal extremities o form a single midline vessel lying between the developing gut, ventrally, and the notoc or , dorsally. As growth of the embryo proceeds this fusion extends forward, but never reacies as far as the pharyngeal arch region (Figs 146, 150 and 152A)

The I St pharyngeal arch arteries disappear at about the time that the 3rd arch are fully differentiated. Involution of the 2nd arch arteries follows as the 4th arc ar cn mature and increase in size (Figs 147, 148 and 203) These changes are possibly to ^ j

with the relative caudal displacement of the heart and aortic sac, for the more cau a y si u



3rd and 4lh arch ancnes wU tap ihc Wood which ongmalU passed to the cranial two pain The latter howesef, do not completelj disappear but persist at least m part of their course, as the maxxUaT) arter> (ist arch) and the stapedtal artcr> (and arch) further their \entral portions ma^ contribute to the de\elopmcnt of the external carotid arterj

\t about the 5 mm stage (Fig 148) a pair of phanngcal arch arteries appears in the mesoderm of the 6th arches These soon gne off descending branches to the plexuses of the lung buds and are therefore called the pulmonary arches Shortlj after their ippcarance trinsent phar>ngcal arch arteries can be found m the 5th arches

Tir 147 — Tte leli s dc of a modd of ihe cranial pari of ihe nenous s' stem and of ibe heart and branchial arch arinies 1134 mm human embr>o (after Congdon) Onlv the endoth Iiat h art tuljc >s shown The first three arch arteries are present and the lourth irch arten is descloping (

In embr>os of about to mm (Figs 149 and 150) the 3rd 4th and 6th arch arteries arc Mcll deicJoped and the bufbus cordis has become di\idcd b> the growth of the spiral bulbir septum The distal portion of the septum extends into the aortic sac (Fig 141) m such a manner that the blood which enters the bulbus from the right ventricle comes to empty into the dorsal part of the aortic sac and thence into the 6th arch arteries alone w hile that from the left \ entncle w distributed to the 3rd and 4th arch artcncs by way of the ventral part of the sac The latter now shows right and left extensions or horns (Fig 150)

At about the 13 mm stage several changes occur which alter very considerabh the original arch arterial pattern so that subsequent stages may be referred to as post branchial (Congdon




dorsal AORTA

3RD pharyngeal POUCH


dorsal rudiment of







1922), These changes (Figs 152 and 188) include the disappearance, on each side, of the portion of the dorsal aorta between the points at which it is joined by the 3rd and 4th arch arteries This portion of each dorsal aorta is called the ductus caroticus (Figs. 183 and 361) and Its disappearance seems to be the result of the altered haemodynamic conditions in the pharyngeal arch arteries which accompany the appearance of the embryonic neck and the “descent” of the heart. At the same time, in mammals, the pharyngeal arch arterial pattern is greatly modified by the disappearance of the segment of the right* dorsal aorta between the point of attachment to it of the right 4th arch artery and its junction with the left dorsal aorta to form the single descending aorta (Figs. 152B and 188-190). As a necessary accompaniment of the disappearance of this segment of the right dorsal aorta the lateral portion of the right 6th arch artery, beyond the origin of the branch to the right lung bud, also disappears. Blood from the heart can now pass to the single descending aorta only by way of the left 4th and 6th

arch arteries The terminal part of the latter, beyond the origin of the branch to the left lung bud, persists until full term as an important foetal vessel, the ductus arteriosus (Figs 151, 152, 161 and 213), ^vhlch conducts most of the blood from the right ventricle to the descending aorta (see foetal circulation, page 1 69) The aortic sac, its left horn and the left 4th arch artery form the arch of the definitive aorta which receives its blood from the left ventiicle The right horn of the aortic sac elongates to become the innominate artery The pi oximal pai t of the left 3rd arch artery becomes the left common carotid artery and its distal portion forms the commencement of the left internal carotid artery (as far as the point to which the left ductus caroticus was attached, Figs 152 and 149)The innominate artery teiminates by giving origin to the right 3rd and 4th arch arteries The foimer of these becomes the right common carotid artery and the commencement of the right interim carotid aitery (as far as the point to which the right ductus caroticus ^vas attached. Fig The right 4th arch artery forms, as will be described later, the stem of origin of the right subc avian artery The left subclavian artery arises by the hypertrophy of a segmental branch of the e dorsal aorta, at, or near, the point at which the latter is joined by the left 4th arch artery (Fig and see later)

The external carotid arteries arise as new branches (Congdon, 1922) from the ventral aspec of the 3rd arch arteries (Figs. 152, 189 and 190) which probably link up M'lth ^ channels left by the retrogression of 1st and 2nd arch arteries The points of origin o


Fig 148 — The left lateral aspect of a model of the pharynx and branchial arch arteries in a 5 mm human embryo (after Congdon) The ist and and arch arteries have retrogressed, the 3rd and 4th arch arteries are complete, and the dorsal and \ entral endothelial sprouts of the 6th (pulmonary) arch artery have nearlv met From the ventral sprouts plexiform vessels pass to the lung bud

  • In birds it is the left side of the branchial arch arterial pattern which undergoes considerable ”hc

lodem reptiles both dorsal aortae persist, but that of the left side is ne\er so well devclope

In modem right (see Goodrich, 1930, for details)



cxterml carotid \esscls diside the 3rd arch arteries into common and mtcrnal carotid segments Each internal carotid artery is formed m its first portion b> the dorsal part of the 3rd arch arter) and be>ond this (crannl to the obliterated ductus caroticus) b> the segment of the ongiml dorsal aorta of the side concerned (Figs 15a, 189-190) In the region of the forebrain each internal carotid arter> gives off an ophthalmic branch to the developing eve vesicle and divides into three branches (Figs 147 and 361), an anterior anbra! arterv a middle cerebral arterv and a branch v\hich initiall} represents the postenor cerebral arterv but later becomes modified to form the posterior eommumcahng arter) passing to the basilar arterv (see later) so that the deUnxiwt. f oslenor cerebral irltv) appears to bea branch of the latter (Fig 203) For details of the dev elopmenl of the cranial arteries the

reader is referred to Padget (1948)

The changes vihich have just been described result m the establishment of the definitive arterial pattern Frequent anomalies arc found in this pattern and result from the persistence of channels that normally disappear or from the disappearance of normally persisting vessels The commoner varieties of atypical pattern are summarized m I ig 153 In the branchial phase of develop ment the nerves of the pharvn^cal arches characteristicallv pass to ihetr distributions m the mesoderm of the arches lateral to the dorsal aorta of the side concerned and in the substance of the arches pass mediallv in front of the corresponding artery to supply the covering mucosa of endodermal origin iFigs 152 183 and 218) The Cth arch nerve hovievcr although it passes lateral to the dorsal aorta 1$ caudal to the 6ih arch artery as it passes towards the developing larynx When the primitive branchial arch pattern of the artencs is interrupted by the changes that have been described the ncuro vascular relations are much altered (Fig 152B) as the disappearance of certain of the primitive artencs allovis the nerves to mo\c to new

Fio 149 — The left lateral aspect of a model of the pharynx and branchial arch arteries in an 11 mm htman embryo (after Congdon) The 6ih (pulmonary) arth artery 1$ complete and the 3rd arch ariery is bent cranially at its dorsal end and its stream is about to be deflected in that direction

positions The nerses (Vth Vllthaod

I\th) of the first three arches arc always lateral to the internal carotid artery (Fig 183) which represents the cranial part of the dorsal aorta The nerve {superior lar^rigeal) of the 4th arch however no longer preserves this relationship as the ductus caroticus segment of the dorsal aorta disappears and the nerve passes deep (medially) to that portion of the 3rd arch artery which becomes the commencement of the internal carotid arterv As the 6th arch nerves are caudal to the corresponding arteries they are prevented in the branchial phase of development from slipping forward as the neck elongates When the nghl homologue of the ductus arteriosus disappears however the nerve {right recurrent laryngeal) of this side moves cramally to become related to the right 4th arch artery (root of nght subclavian artery) below which it passes to lb. distribution in the laryn^^eal region The persistence of the ductus arteriosus on the left



side prevents such a migration of the left recurrent laryngeal nerve so that, even m the adult, this

nerve passes caudal to the ductus arteriosus arfenojum).

In addition to having important relationships to the arch arteries the pharyngeal arch nerves give a specialized supply to them (Fig 152B) which forms the anatomical basis for the pressor-receptor mechanisms of the carotid sinuses, the aorta, the right subclavian arteiy and possibly, the pulmonary artery and ductus arteriosus (Koch, 1931, Boyd, 1941). The corohrf sinuses situated on the 3rd arch portions of the internal carotid arteries, are supplied by e 3rd arch {glossopharyngeal) nerves. The aorta and right subclavian arteries (4th arch vessels) Le innervated by branches of the 4th arch nerve {superior laryngeal) either directly (as m the

rabbit) or by way of the vagal trunk (as is usual in man) . These pressor-receptor regions of the raouu; y y & branchial arch arteries have associated with

them specialized groups of cells which act as chemo-recepiors (see carotid body, page 330).








The branches of the-dorsal aortae appear very early and can be divided into three groups (Fig. 154) (0 splanchnic

arteries, to the gut and its derivatives; (2) lateral, splanchnic arteries, to the intermediate mesoderm; and (3) dorso-lateral, somatic intersegmental arteries which take origin from the aortae between successive somites and are distributed to the plexuses which supply the somites, the body wall and the walls and contents of the spinal canal

(1) The ventral branches (splanchnic) of the aortae are initially distributed to the yolk sac, as paired primitive vitelline and to the allantoic mesoderm, as the paired umbilical arteries (Figs. 77 and 200). are more or less segmentally are distributed to the visceral '

pleuric) mesoderm and the d^riv^f J die gut, yolk sac and associated struck They are soon reduced in numbe y appLance of most of the stems of ori|n

aS by the fuston. .n “1 rf th« 

fusion of the dorsal aortae, of

which persist to form trunks, the

in the dorsal mesentery The latter are represented in later stage® by ^ d,stributed to coehac, superior mesenteric and inferior mesenteric {^rgy. 2W, 203 an ^ probably represent the the fore-, mid- and hind-guts respectively (Chapter X). thoracic and fifth thoracic

original splanchnic segmental vessels of the seventh cervica , rjong by progressive presegments which migrate from their primitiw levels to ^ oesophageal arteries

aortic anastomoses with successive new caudal stems, i ne umbilical arteries are

represent splanchnic segmental vessels cranial to the coe ^^j^^ ^iooed to supply the mesoderm the pair of splanchnic segmental vessels which are precocious y allantois (page 7^) • They

of the comtecting stalk Ld they can be regarded as the reach the

also migrate caudally, with the growth m length o the ^.ons with the fif*

level of the lower lumbar segments where they form a



Fig 150 — The \entral view of the branchial arch arteries in an 1 1 mm human embryo (after Congaon)


  • 59

lumbar somatic intersegmental arteries, the anastomoses lying dorsal to the ureters The portion of each original umbilical artery between the dorsal aorta and the anastomoses then retrogresses and disappears so that the stem of each defimtne umbilical artery is of lumbar intersegmental origin and passes posterior to the ureter The external and internal tlioi. arteries on each side arise as branches of the intersegmental stems Each umbilical artery, which originally was the mam trunk eventually comes to appear as a branch of the corresponding internal iliac artery After birth each umbilical artery is represented bv the superior tesical branch of the internal ihac artery and the obliterated artenal stem which passes from this branch to the umbilicus

(2) The lateral branches (inter mediate splanchmc arteries) of the dorsal aortae vvhich supply the intermediate mesoderm (Fig 154A) are only well dev eloped m the regions of the dev eloping pro meso and meta nephroi These branches arc represented in the adult by the renal suprarenal phreme and spermatic or oianan arteries

(3) The dorso lateral (somatic inter segmental) branches of the dorsal aortae extend from the level of the occipital somites to the sacral region They arise on each side from the dorso lateral aspiect of the corresponding aorta and extend round the ventro lateral surfaces of the vertebral bodies to the anterior aspect of the heads of the ribs where they divide into dorsal and ventrolateral branches (Fig 154) the former are initially larger but the latter increase rapidly in size and soon appear as the main continuations of the ve'scls The dorsal branches pass backwards between successive nbs and transverse processes and give off medially directed neural branches to the spinal canal meninges and later the spinal cord The ventro lateral branches extend mto the bodv wall, along the course of the anterior primary divnsions of the spinal nerves and after giving off lateral branches terminate vcnlrallv bv anastomosing m the midline with their fellows of the opposite side

In the thoracic and upper lumbar regions the intersegmental artenes persist throughout life as the serially arranged intercostal and lumbar artcncs Those m the occipital region (hypoglossal anencs) soon retrogress and those m the cervical and sacral retoons are much modified by the dev elopment of the v ertebral and iliac artenes respectiv ely The changes m the cervical intersegmental arteries are to be correlated with the obliteration of the ductus caroticus and the formauon of the neck and fore limb they consist m the elaboration of longitudinal anastomoses which are formed between successive intersegmental artenes in pre costal post-costal and post transierse positions (Figs 154 and 203) and in the disappearance of the stems of origin



of the upper six cervical intersegmental arteries (Fig. 152). The post-costal anastomosis, between the levels of the first and sixth cervical segments, becomes enlarged to form the portion of the vertebral artery lying within the costo-transverse foramina of the cervical vertebrae This vessel consequently appears as a branch of the dorsal division of the seventh cervical mtersegmental artery. The portion of the vertebral artery lying on the arch of the atlas represents the spinal branch of the first cervical intersegmental artery and its continuation fuses wth its fellow of the opposite side to form the basilar artery (Fig, 334A), which may be regarded as a pre-neural anastomotic vessel The basilar artery extends forward to the region of the anterior part of the pontine flexure where it bifurcates to form two large branches which complete















recurrent N ^ \ \ ^ innominate' A \





Fig 152 — Diagrams of the branchial arch arteries (A) and of the definitive aortic and pulmonary trunks (B) to show the derivation of the branches of the latter. The relations of the branchial nerves to the arteries are also shown

the circle of Willis, by joining the posterior cerebral arteries and eventually appear as the mam stems of the ongin of these vessels. . .

The origin, from the dorsal aorta, of the seventh cervical intersegmental artery of eac side is at first caudal to the dorsal attachment of the sixth aortic arch. With the e onga ion of the neck and the descent of the heart, and before the time of disappearance of the segmen of the right dorsal aorta between the attachment of the fourth aortic arch and the juncticm the two dorsal aortae, this origin migrates cranially until it is opposite to the dorsa . the 4th branchial arch. On the left side it now represents the stem of origin, tea arch, of the left subclavian artery; its dorsal division is the origin of the verte ra ar ery its ventral division together with the lateral branch constitutes hnncb

of the left arm (Figs 152B and 154B), The portion anterior to the origin oft ^ ^ forms the stem of the internal mammary artery which is continued caudally to t e a omi


b> a \entral anastomotic chain (Fig 154) On the nght side the subclatian artery and its branches arise in a similar fashion but owing to the interruption of the dorsal aorta on this side the right 4th arch arten discharges exclusi\cl> into the subclatnan trunk and becomes its first poruon If on this side, the sc\enth intcrseg mental artery does not migrate cramalU or if the break in the dorsal aorta is abnormal or is associated with retrogression of the right 4th arch arter) then the right subcla\aan arterj (Fig 153) appears as a branch of the arch of the aorta beyond the left subcla\nan arlcr> and passes to the nght side behind the oesophagus This abnor mality is not uncommon and has some clinical significance

Persistence in the ccr\ical and upper thoracic regions of pre costal anastomoses gi\ c origin to the Ihm-cemcal and to the superior intereostal stem Persistence of the post transserse anastomoses forms the deep eerneal artery

In the sacral region the intenegmental arteries are much modified b> the changes (page 158; tvhich result in the linking of the umbilical arteries to the fifth lumbar intersegmenial arteries as branches of this \essel and the former taps the intenegmental \essels of the sacral region "hich then appear as its panetal branches Consequently the ongmal dorsal aorta in the sacra! region is much reduced m size to form the middle sacral arterv This \essel termi nates m front of the coccs'x b> forming with adjacent \cins a complicated arteno \enous anastomosis called the glomus eoee}geum in %\hich the \ascular celts undergo a curious epithelioid change

Fic 154 — Schemej to show the distnbution of the inicrscgnicnial artrnes V — trunk region

B— lower cer\ leal (arm bud) region


Fir I33 — Schemes to iho abnormalities in the deselopmenl of the branchial arch artenal pattern Persisting $\-stemic arteries arc repre seated m u lid black the pulmonars trunk its branches and the ductus anenosus are stippled normal pattern B— double aortic arch C — abnormal orimn of right subclavian arterv D— right aaruc arch E — absence of both common carotid arteries F— extreme degree of co>arciauon of aorta the descendin'* aorta being supplied bv the ductus arteno us alone

The internal and external iliac artenea anse




The vascular plexuses of the limb-buds are initially supplied by four or five consecutive intersegmental branches of the dorsal aortae at the levels at which the limb-buds are situated Very early, however, the lateral branch of the seventh cervical and branches of the fifth lumbar intersegmental arteries become much enlarged to form the axial arteries of the upper and lower limbs respectively In the arm this axial artery terminates in a capillary plexus from which, later, digital branches arise The proximal part of the artery can be recognized as the brachial artery, its distal portion is the interosseous artery The ulnar and radial arteries arise comparatively late m development as new vessels

In the leg the original axial artery is on what, m the adult, becomes the dorsal aspect* of the thigh and is a branch of the internal ihae It accompanies the sciatic nerve and terminates m a plexus from which the digital branches arise Later a new vessel, the femoral artery, appears in a plexus on the future ventral aspect of the thigh and, by linking with the axial artery m the popliteal region, comes to form the main blood supply to the limb The original axial artery is represented in the adult by the arteria comes nervi ischiadici and probably the distal part of the peroneal artery The obturator artery represents a supply to the plexus on the medial side of the thigh and it arises comparatively late m development. The anterior and posterior tibial arteries represent later additions to the vascular pattern as does also the greater part of the popliteal artery for this vessel is initially ventral to the pophteus muscle (For details of the development of the limb arteries consult Senior, 1919, 1924, 1925 and 1929)


The veins of the early embryo may readily be grouped into —

{a) The vitelline system consisting of right and left vitelline {omphalomesenteric) veins which arise m the splanchnopleunc mesoderm of the yolk sac wall and pass to the caudal edge of the septum transversum medial to the mtercoelomic communication (Figs 77A and B, 126, 127 and 144) Here they join the corresponding primitive sinus venosus The plexus on the caudal portion of the yolk sac wall commumcates with the umbilical veins by way of vitelloumbilical anastomoses

{b) The umbilical system consisting of the venous tributaries in the chorionic villi (page 72) and the right and left umbilical veins which may be umted to form a single vein in the connecting stalk The umbilical veins pass through the connecting stalk to the caudal end of the primitive umbilicus (Figs. 77, 144 and 200) Here they enter the lateral margin of the somatopleure and pass m it anteriorly around the yolk sac stalk, but separated from the latter by the communication between the intra- and extra-embryonic coeloms, to enter the substance of the developing septum transversum where they join the corresponding primitive sinus venosus (Figs 77A and B, 126 and 127)

(c) The cardinal system consisting of veins which are entirely intra-embryonic From this system the main systemic veins of the adult are derived

Most of the embryonic veins arise as capillary plexuses which first increase in complexity by sprouting and anastomosis and then fuse and enlarge giving rise to fewer and larger channe . Many of these plexuses are transitory, retrogressing as the organs drained by them diminis in size or migrate to other regions As the organs enlarge or enter new regions new vans appear and these, m turn, with subsequent changes, may atrophy and be replaced ^ ° veins. Some foetal vessels which ^re required during intra-uterine life undergo atrop shortly after birth (page 171)

  • It must be kept in mind that the lower extremity has undergone a considerab e surface

development, indicated by the fact that the patella was originally on the dorso-latera , >

and that ihe popliteal fossa was on the ventro-medial, or flexor, surface in the embryo.




The Mtelhne \cms hnt pass along each side of the anterior intotmal portal (higs X26 and 155A) to enter the septum transtersum soon however both m the substance of the septum transversum and around the developing duodenal loop the two vitelline veins form an anasio* mosing plexus The extension of the cordsof liver ccllsvvithin the septum tramv ersum encroaches on the mtraseptal portion of the vitelline plexus and breaks it up into primitive hpalic sinusoids Anterior to the iner tlie stems of the vitettmc veins stiU enter the corresponding pnmitjve sinus venosus as htpalo cardiac ckanneli (Streeter 1942) The right channel later becomes greatly enlarged to form the termination of the tnjinof una ca a, the left one is transitory

Due to the presence of the relatively thick dorsal and ventral mesenteries of the duodenum, the ventral one of which u anatomically almost a part of the septum transversum the nght and left vitelline veins m this region arc connected both vcntrally and dorsally to the duodenum

Fig 153 — Schcioei of the devclopmenl of ihc inira embr>onic veins in embr>os V — at the 4 mm stage B — at the 10 mm stage The veins of the head are seen in profile

by a rich plexus of duodenal veins WTieo the stomach and duodenum elongate and rotate from their original mid sagittal position (Fig 200) to their adult position (Fig 212), it is easy to understand that m seekint, the most direct route to the liver the venous blood does not follow the original right and left sides of the now transversely looped duodenum but instead cuts veross from one vatelhne vein to the other throujjh the connecting plexus The blood in the right vitcihne vein which lies along the caudal portion of the duodenum tends to flow across the ventral anastomotic plexus to the left vitelline vein vvhicb in turn sends its blood straight towards the liver by way of a dorsal anastomosis with the hepatic end of the persistent part of the nght viielhne vein The portal vein thus formed does not spiral around the duodenum as so commonlv described and illustrated but instead is short and straight with the duodenum spiralling around it Such changes in vascular pattern are common and the case with whirh. thev take place can be readily understood if the two following basic facts are appreciated



(i) the essentially plexiform nature of the embryomc vascular system; and (2) the natural tendency for blood to seek the most direct route of flow because of hydrodynamic factors. When the superior mesenteric vein is differentiated in situ in the mesentery it drains into the left vitelline vein At a later stage the splenic vein, owing to the herniation of the midgut, receives the inferior mesenteric vein and joins the left vitelline vein at a slightly higher level (Fig. 157A) With the atrophy of the vitello-intestinal duct the distal portions of the vitelline veins retrogress


Soon after the vitelline veins have been broken into sinusoids by the proliferating liver epithelium, the latter extends laterally in the septum transversum with the result that the intraseptal portions of the umbilical veins are also enmeshed and broken up into sinusoids (Figs. 1 55 and 223). The proximal stalks of attachment of the umbilical veins persist temporarily, but by the 5 mm. stage all the blood in the umbilical veins passes into the liver where these vessels communicate freely with the vitelline sinusoids At about the 6-7 mm stage the right umbilical vein undergoes atrophy and disappears with the result that all the blood from the placenta enters the embryo through the left umbilical vein into the hepatic sinusoids With the elaboration of the right side of the sinus venosus an enlargement of the hepatic sinusoidal communication occurs between the point of entry of the left umbilical vein and the right hepato-cardiac channel (persistent proximal part of the right vitelline vein); this channel is the ductus venosus (Figs. 155B, 157A, 2 13 and 214). Blood entering now from either the umbilical or vitelline systems can either pass by way of the ductus venosus to the right atrium or it can pass into the venae advehentes to the liver sinusoids from whence it is collected by the venae revehentes to the right hepato-cardiac channel The venae advehentes later become the branches of the portal vein in the liver and the venae revehentes are the tributaries of the hepatic veins. After birth the left umbilical vein and the ductus venosus are obliterated and they are represented in post-natal life by the ligamentum teres and hgamentum venosum respectively


Anterior Cardinal Veins. The venous drainage of the head end of the early embryo occurs by way of right and left anterior cardinal veins which receive tributaries, which have probably developed in situ, from three plexuses related to the mesenchyme surrounding the primary cerebral vesicles (Figs 145, 155 and 157) Each anterior cardinal vein runs caudally to join the corresponding posterior cardinal vein to form the right or left duct of Cuvier The cramal part of each anterior cardinal vein is frequently called the primary head vein; this vein lies medial to the trigeminal ganglion, but ventrolateral to the auditory vesicle and roots 0 origin of the glossopharyngeal and vagus nerves. During the 14-18 mm. stages, when t e meninges are differentiated, a cleavage occurs between the superficial and deep portions o the tributaries of the primary head vein so that the latter, together with the superficial parts of the plexus, becomes a dural venous system while the deep parts of the plexus persist as t e cerebral veins

The subsequent changes in the dural veins have been described in detail by Streeter (19^ )• Briefly these changes are as follows (Figs. 155 and 157) —

(1) The increase in size of the otic capsule results in the formation of a secondary channe , dorsal to the capsule, which connects the middle dural plexus with branches of the pos erio plexus

(2) The anterior dural plexus then anastomoses with the middle plexus ivhich no drains it.

(3) The portions of the primary head vein immediately anterior and trigeminal ganglion retrogress leaving the intermediate portion as the definitive sinus ^vhich soon establishes new communications (superior and inferior petrosa nnuses) vsi posterior part of the primary head vein.


1 6;

(4) Nc^v vessels the suptnor sagittal straight and infenor sagittal sinuses are elaborated from the midline portions of the onginal plexuses

{5) The superior sagittal and straight sinuses open into the trunk connecting the middle and posterior plexuses and this trunk finall> replaces the latter plexus

The anterior cardinal veins arc at first short but with the descent of the heart the> elongate At the same time the cervical segmental veins including that one receiving the venous drainage of the upper limb v\ hich originallv drained into the cephalic portions of the posterior cardinal veins become transferred to the anterior cardinal veins At about the 22 mm stage the two anterior cardinal v eins become connected m the low er cerv ical region b> a iratisv erse anastomosis (Fig 157B) which directs the drainage from the left antenor cardinal vein to the lower part of the right one this is accompanied in man although not in all mammals bv the obliteration of a portion of the left duct of Cuvier As a result of these changes all the blood from the head and neck and from the upper limbs novv reaches the nght duct of Cuvier which together with the terminal portion of the right anterior cardinal vein becomes the superior tena eata The portions of the anterior cardinal veins cranial to the junction with the veins from the upper limb (subclavian veins) are now called the internal jugular veins Each external jugular vein antes as a secondary channel from a capillary plexus in the facial region and drains the face and side of the head and neck into the subclavian vein (Fig 157B)

Posterior Cardinal Veins These veins arise slightl) later than the antenor cardinal veins at about the 14 somite stage (Figs 144 ind 145) as two longitudinal vessels m the dorso lateral portion of the urogenital fold (Figs 156 207 and 231) Cranially each

postenor cardinal vein which is concerned • c bo e

pnmanlj mih the drainage of the bod> Fic 156 -A nannene .eeiion to .ho. mesonephros and spinal cord terminates bv schematicallv the mier rebtioruhips of the

joining the anterior cardinal vein in the lateral lon?)iudmaI vcnoui channel* m the po*

r i_ y. . tenor abdominal wall

part ot the septum transversum to form the

duct of Cuvier (common cardinal vein) which passes medially to join the corresponding sinus venosus (Figs 219 and 222) In subsequent stages of development these postenor cardinal veins

are soon rcmforccd by other longitudinal connecting channels which first appear as plexuses along the so-callcd venous lines of the embryo (Fig 156) These secondary channeb which form most complicated paiiems and cventuallv result in the development of the infcnor vena cava and azvgos systems arc —

(1) the subcardial veins

(2) the veins of the thoraco-lumbar bne or lateral svmpathetic line (equivalent to the supracardmab of lower mammab)

(3) veins of the medial sympathetic or azygos line

(4) V eins of the subcentral lines and

(a) veins of the precostal or lumbo-costal hncs


human embryology

-I ne approximate positions nftv,,. i and Robinson, 1027 Se,h’ ^ ^926, 1927 and 1040- Rppo-° ^ (McClure and

attempt to give the eknto/pomL‘‘o7^^ '937).’ The subsequmfd

the above authors. ^ mts ot development, for further detadf?., description is an

Subcandinal Veins S„„ f e *”«der is referred ,„

P- of veins appear, one in the -d^l^U Tereru" a neiv







Left duct OF CUVIER



hepatic segment " OF I V c




Venae REVEMENTES venae

“VEHENTES lHArN^”^T|c /■«voo\^’r.-«-c V

'PHORACO lumbar line,

anI^" ^vbcardinal anastomosis

'°sl,terated post CARDINAL V






PT INNOMINATE V innominate V




inter azygos / / anastomosis f ) azygos V j " 'nter azygos / i anastomosis

f suprarenal





int ear




Ext jugular v SUBCLAVIAN




intercostal LIGI op ■ » MARSHALL 'I" SUP HtMIAZYGOa



Frr o . obliterated / MID \

^57 Schemes showiner eU I SVBCARDINAL V SACRAL

veins* A — at the tc m ^ development and fate oT tl

'5 mm stage, B— foetal stage ^ mtra-embryonic

aj — loetai stage —

from longitudinal anastomoses of th,.

SbabTvTcou T orZZrllT mesonephros. The

lower SLaSr” ,? Z wide vanatmns of mammalian embryos

mZZ Ze Z r ThZnT^ ^nous development in the

e“crmesoneTh germinal emthM"' subcardinal and they dram

spond^ rT t^nateTramahv ™^dial aspect of

ponding posterior cardinal vctt t. ZZ th/ ^55 and 157) m the corre die two^ r by numeroulftransverse anasto iie two subcardinal veins become united bv an

mosZ At to which th 7 v (higs. 155 and 157) m the corrt

cardtna/ n ^ stage the two ^ 7^ ^j^o joined by numerou|ftransverse anasto

ardtml anastomose in front of the lorta become united by an tntersub

orta. A httle earlier than this, 7-8 mm stage, the right


subcard.nal \cm becomes connected enniall) to the hepatic sinuses b) a plexus whtch soon dcselops mto a larqc '.cs'cl the ktpaiu of the inferior \ena ca\a This \essel establishes

a direct pathway front the right subcardinal to the right hepato cardiac channel and marks the first stage m the dc% elopment of the infenor \ena cat a

Lateral Sympathetic or Thoraco lumbar Line Veins Soon after the establishment of the hepatic segment of the inferior \cna cat a a \cnous plexus develops lateral to the sympathetic trunks and dorsr> medial to the posterior cardinal line but antenor to the segmental vessels {Figs 156 and i57/\) This plexus soon become, a longitudinal trunk which has been called by different names eg vein of the thoraco lumbar line para ureteric vein supracardmal \ cm Anteriorly it terminates in the posterior cardinal vein, posteriorly especially on the right side it soon establishes anastomoses vsith the corresponding subcardmal vein By the 20 mm stage the greater part of the thoraco lumbar vein has retrogressed leaving only that portion on the right side caudal to the level of the major anastomosis with the right sub cardinal vein This anastomosis, md the portion of the nght thoraco*lumbar vein caudal to It persist as the infra renal portion of the definitive inferior vena cava The definitive inferior vena cava therefore is made up of the follov^mt, portions (Fig >572) —

(t) A small portion of the right posterior cardinal vein {or the caudal anastomosis between the postenor cardinals)

(2) The caudal portion of the right thoraco lumbar vein

(3) The right thoraco lumbar subcardmal anastomosis

(4) The intermediate portion of the nght subcardmal vein

{5) The anastomosis between the nght subcardmal vein and the right hepato cardiac channel

(6) The terminal portion of the hepato cardiac channel which probably represents the termination of the right vitellme vein

The persistent portions of the subcardmal veins not included m the inferior vena cava become the veins of the gonads and suprarenab The intersubcardinol anastomosis forms that part of the left renal vein between the attachment of the genital vein (left subcardmal) and the inferior vena cava The remaining portions of the left renal vein and the right renal vein are metanephne veins which dram into thesubcardmals The complicated developmental history of the inlcnor vena cava alTords the basis for explanation of its frequent anomalies

Medial Sympathetic or Azygos Line Veins At about the svme period as the formation of the lateral sympathetic venous line a longiludiml plexus of veins appears medial to each sympathetic trunk These medial sympathetic veins as Reagan {1927) first demonstrated give rise to the greater part of theit^gM tentiar system Superiorly they terminate in the postenor cardinal veins (Fig 137A) infenorly they may communicate with the sub cardinal veins In the thoracic region these veins of the azygos line dram the segmental (mtercostil) veins which pass to them dorsal to the sympathetic chain (Figs 156 and 157B) The two azygos line veins arc brought into communication by way of anastomoses to the subcemral veins which form longitudinal channels dorsal to the aorta and by mtersubcentral anastomoses (Fig 156) ^Vuh the decrease in importance of the left duct of Cuvier the blood in the left azygos system below the level of the third left intercostal vein drains across the middle line behind the aorta to the nght azygos system which in turn drains into the persistent cephalic termination of the right posterior cardinal The second and third intercostal veins of the left side retain their connexion with the cephalic termination of the left postenor cardinal V em W uh the obliteration of the lateral portion of the left duct of Cuvier the blood from the second and third leftfintercostal spaces afterentenngthe pcnistent portion of the left postenor car dinal vein passes to the left innominate vein hy way of the caudal portion of the left anterior cardinal vein The left superior inlereoslat vein thus receives contributions from the left posterior


1 68

and anterior cardinal veins. In rare cases in man, and normally in some mammals, this potential communication may remain patent as a left superior vena cava. For details of variations of the azygos venous system, the reader is referred to Seib (1934)

When, m normal development, the left duct of Cuvier retrogresses its medial portion persists as the lateral part of the coronary sinus Endothelial sprouts extend from the sinus into the cardiac musculature to give origin to the coronary veins. The lateral portion of the left duct of Cuvier usually persists as a small oblique vein (of Marshall) which may be attached to the left superior intercostal vein


The lymphatic system is closely related to, and develops concurrently with, the venous system and like it acts as a channel for the return of fluid from the tissues.

There are two conflicting conceptions of the origin of the lymphatic system —

Sabin (1902 and later papers) believes that all lymphatic channels are developed as sac-like outgrowths of venous endothelium. A pair of these occur in the neck, ihe. jugular lymph sacs, a pair near the iliac veins, the iliac lymph sacs, and two unpaired near the veins of the posterior abdominal wall, the retroperitoneal (or mesenteric) sac and the cisterna chyli By continuous elongation, centrifugal growth and branching they invade most of the tissues of the body. The original connexions with the veins may be retained as the definitive connexions of the adult lymphatic system or may disappear entirely or be re-established later.

Kampmeier (1912), Huntington (1914) and Zimmermann (1940), on the other hand, believe that the lymphatic system arises by confluence of perivenous mesenchymal spaces to form larger spaces, these in turn becoming confluent to form continuous vessels which eventually open into the venous system The cells lining the spaces are at first undifferentiated mesenchyme, but later become flattened to form the endothelium of the lymphatic vessels

„ In the human embryo the lymphatic spaces whic

'mg lyn^ hatm mm' represent the beginning of the definitive lymphatic system

human embryo (After Sabin, m appear in the jugular region of each Side and coalesce

Keibel and Mall ) form the jugular lymph sacs at the lo-ii mm. stage.

The jugular lymph sacs become closely associated wit the lymphatics of the arm bud From the caudal parts of these lymph sacs the cranial part of the thoracic duct of each side is formed by the union of spaces, or by budding from the existing sac, along the course of the lateral sympathetic vein (Fig 158) These channels become secondarily connected with the developing cisterna chyli to form paired thoracic ducts. Later transverse anastomoses result in most of the lymph reaching the left jugular sac (Fig. I 5 ^) Kampmeier (1928) demonstrated that valves are already present in the early lymphatics 0 the region of the jugular lymph sacs and upper thoracic duct at the end of the second mon of foetal life At the beginning of the fifth foetal month an apparently complete valvu a complement is provided in both the peripheral and deep lymphatics, although not all the va v are fully differentiated. The early development of these valves is some indication o establishment of hydrostatic, and presumably functional, conditions similar to those m


adult In general the de\eIopment of \enous \al\es lags behind those of corresponding Ijmph vessels b\ a month or more


These are developed b\ the aggregation of lymphoblasts in the mescnchjinc surrounding the plexuses of Ij-mphatics which arise from the pnmar> h-mphatic sacs (Figs 159 and 160) The aggregations are first found in 30 mm embryos but Ijinph glands themselves cannot be identified until the 50 mm stage appearing first in the axillary and iliac regions Full histological differentiation of medulla and cortex docs not occur until after birth

During the earl^ Stages of their development the lymphatic vessels for a time contain ervthrobJasts Later the J)7nph glands may also show ciyihropoiesis and thus resemble the haemoljTOph glands of other mammals In yet later stages the IjTnph glands are solely ly-mphocy topoietic and erythrocytes are no longer found in the Isttiph vessels

Fio 159 — Photomicrograph of a section ofadoclop* mg cervical lymph vessel in a 60 mm human embryo It shovs a collection of lymphoblasts

Fic 160 — Pbolomicrograph of a section of a develop ing cervical lymph gland in a 143 mm human embryo Note marginal sinus X c 450


The work of Barcrofl (1936 1946) and of Barclay et al (1939) whichincluded the invest! gation of the course of the foetal blood stream by \ ray cinematography has demonstrated that the foetal circulation is more complicated than was previously realized Although this work has been earned out principally on the sheep foetus there is reason to believe that the findings apply m the mam to the circulauon m other mammalian foetuses although there are, doubtless slight differences in different speacs

The probable course of the human foetal circulation is illustrated diagrammatically in Fig 161 The oxygenated blood returning from the placenta in the umbilical vein passes toward the liver where it is largely short arcuitcd to the infenor vena cava by way of the ductus V enosus As the infenor v ena cava already contains venous blood from the caudal regions of the foetus and as it also receiv es the hepatic veins while the ductus \ enosus itself has been joined by the left branch of the portal vein the blood in the upper part of the inferior vena cava is slightly less oxygenated than the blood in the umbilical vein The inferior caval blood reaches the

1 70















Fig i6i —Scheme to show the foetal circulation An attempt has been made to show schematically the relative degrees of oxygenation m the different vessels (Based on the \vork of Barclay. Barcroft, Bayon and Franklin, 1939, and Windle, 1940) The hepatic veins are not shown in tnis figure For further details sec text


right atrium %\herc it is directed b> the \ahe of the inferior %ena ca\a, towards the foramen ovale Here the upper margin [crista dtndetis of Amoroso et ol 194 ' Franklin 194®) of the foramen separates the stream from the inferior vena cava into two unequal portions The larger of these passes through the foramen ovale into the left atnum where it is joined by some venous blood from the pulmonary veins (m an amount which probably increases as development proceeds) and then passes into the left ventricle The smaller stream of infenor caval blood is directed by the cnsta divadcns into the right atnum where it mixes with the venous blood returning to that cavity by wav of the supenor vena cava and vnth this venous blood passes into the right ventricle The blood from the interior vena cava which passes to the left atnum is then almost entirely unmixcd while the small portion of the oxygenated inferior caval blood passing to the nght ventnclc is mixed with a much larger quantity of superior caval blood with a low oxygen and a high carbon dioxide content

The right v entncular blood passes out in the pulmonary trunk A small portion of it which increases in amount as development proceeds passes to the lungs but most is directed to the descending thoracic aorta by way of the ductus artenosus The left v entncular blood which has a much higher oxvgcn content than that in the nght ventnclc passes out in the aortic trunk and is distnbuted chiefly to the aricnes of the head neck and upper extremities These regions arc therefore with regard to the supply of oxygenated blood in a pnvalegcd position when compared with the caudal regions of the body The left vcntncular blood that does not pass into the carotid or subclavian trunks passes down the descending aorta and mixes with the large quantity of poorly oxygenated nght vcntncular blood from the ductus artenosus The resulting relatively poorly oxygenated blood m the descending aorta after some of it has been distnbuted to the abdominal and pelvic viscera and to the body wall and lower bmbs passes out in the umbilical artenes which are the mam continuation of the foetal internal iliac artenes to the placenta where it circulates in the capillanes of the valh (Figs 70 and 7a) and IS again oxygenated

The placenta acts as an organ for the transfer of oxygen and nutntive matenal from the maternal blood stream to the foetal circulation and of carbon dioxide and mtrogenous products from the foetal to the maternal circulation Most of the blood returning to the umbilical vein passes directly through the ductus venosus to the nght atnum but some passes directly through the liver and this may account in part for the relatively large size of this organ in foetal life and at birth The liver dunng early foetal stages is actively haematopoietic (pages too and 2o8) In some mammalian embryos (pig horse) a ductus venosus never forms and in these all the umbilical venous blood passes through the liver sinuses

Only a relatively small volume of blood is returned from the non aerated foetal lungs to the left atnum by the pulmonary veins though this amount increases considerably in the last month of foetal life Hence the oxygenated artenal blood at a relatively higher pressure passes readily through the flap mechamsm of the foramen ovale into the left atnum


Very soon after birth and probably within a few minutes of the first breath changes occur m the blood vessels which result m the establishment of the post natal circulatory pattern The most readily observable of the changes is the contraction of the two umbilical artenes in the cord which within a few moments cease to pulsate and allow no further blood to leave the bodv of the child The umbilical vein and ductus venosus also contract but not so rapidlv as the umbilical arteries Consequentlv much of the blood in the placenta can be drawn back into the child (50 cc in the first minute 100 cc by the thirtieth minute Haselhont and Allmeling 1930) if the cord is not tied immediatclv The obliteration of these vesseb is m part due to an active contraction of their muscular coats and in the case of the ductus venosus may be due to a nervous reflex (Baron 1^2) If nervous control plays a part in the con traction of the umbilical artenes and vein however it can only be operative in their intra embrvome portions as the portions m the cord are devoid of a nerve supply Couicidentallv



with these changes, and as a result of the sudden contraction of its richly muscular coat, the ductus arteriosus narrows so that no blood can pass through it (Barcroft, 1936) and all the blood from the right ventricle consequently passes into the lungs by way of the pulmonary arteries The closure of the ductus may be under nervous control as it certainly possesses a specialization of its tunica media to serve as a sphincter, and has both afferent and efferent nerve endings (Boyd, 1941; and Noback et al , 1951)

With the first breath the lungs expand and consequently the pulmonary vessels increase in size though probably not as much as was previously thought, for Patten (1930) has demonstrated that the pulmonary circulation in the last month of foetal life is considerable. The contraction of the ductus arteriosus, diverting all the right ventricular output to the pulmonary arteries, and the expansion of the lungs result in an increase in the flow of pulmonary venous blood, now oxygenated, to the left atrium. Hence, while the blood return to the right atrium IS decreased (by the absence of the umbilical blood from the placenta and the fact that the right ventricular blood no longer contributes to the systemic circulation) that to the left atrium is increased. The result is an increase in the pressure of the blood in the left atrium relative to that in the right atrium which is sufficient to cause a cessation of blood flow through the foramen ovale and to force the flap-like valve, formed by the persisting part of the septum primum, against the margins of the foramen.

While the physiological changes in the foetal circulation at the time of birth are sudden, the anatomical changes which result m the obliteration of the vessels are slow, probably occupying at least six months. In the blood vessels the change is an obliterative endarteritis which usually results in the complete disappearance of the vessel lumen, the fibrosed walls, however, persist and are commonly called ligaments in the adult. The obliterated umbilical arteries become the lateral umbilical ligaments, the intra-abdominal part of the (left) umbilical vein becomes the hgamentum teres of the liver, the ductus venosus becomes the hgamentum venosum, and the ductus arteriosus becomes the hgamentum arteriosum The valve of the foramen ovale also, but even less rapidly, fuses to the left margin of the foramen ovale, and in most individuals this opening is eventually completely closed. In many adults, however, a probe can be passed obliquely from one atrium to the other, through the upper part of the fossa ovalis (for a review of the birth changes in the foetal circulation see Barron, 19445 Barclay et al , 1944) For a review of the whole problem of the physiology of the foetal circulation, including heart, vessels, and the blood itself, see Windle, 1 940


1. Malformation due to Arrest of Development.

A. Atresia or stenosis of pulmonary or aortic trunks or of mitral or tricuspid orifices. These anomalies are frequently associated with compensating defects of the cardiac septa, e g , m the so-called “Tetralogy of Fallot” in which there is pulmonary stenosis or atresia with a patent mter-ventricular foramen, and consequently, a “venous-arterial shunt resu ting in congenital cyanosis.

■pB. 'Defective closure of foetal openings —

1 . Localized defects of development of the interatrial septum, e g , persistent forame ovale resulting in a vascular “shunt” which is continued after birth

2. Localized defects of the inter-ventricular septum, e g , persistent inter- ventricul foramen resulting in an “arterio-venous shunt” after birth.

3. Complete absence of cardiac septa resulting in cor biloculare (one atrium and ventricle) .

..^,4 Gross defects or absence of the inter-ventricular septum resulting m cor trilocul (two atria and one ventricle)



5 Absence of tbe aortico bulbar septum lesulung m persistent truncus arteriosus

6 Partial defects of the aortico bulbar septum resulting in a commumcation betueen aorta and pulmonary artery

7 Patent ductus arteriosus (persistence of the foetal communication betw een pulmonary aiter> and aorta after birth resulting in an arteno venous shunt )

n Heterotaxis (revcnc rotation and mirror imaging)

A Situs inversus viscerum (complete or mcomplete transposition of viscera including heart)

r.B Dextrocardia (heart transposed but remainder of the viscera of normal asymmetricil pattern)

C Transposition of aortic and pulmonary trunks either complete or incomplete due 10 a rotation of the aortico bulbar septum m a reverse direction When the transposition IS complete the aorta anses from the right ventncle These conditions are associated in surviving individuals, with defects of the septa and persistence of the duCtus arteriosus

III Displacement of Heart

\.A Ectopia cordis— heart exposed on chest wall owing to faulty development of sternum and pericardium

B Faulty descent of the heart which may be higher than normal

IV Abnormal Growth

A Congenital tumours of cardiac muscle (Rhabdomvoinata)

B Supernumerary cusps of the cardiac valves due to atyincal div ision of the cusp primordti \ Aortsc Arch and its Branches

V.A Double aorta Due to the complete persistence of both aortic arche and the related parts of the dorsal aortae

>.B •' Right aortic arch Due to persistence of the fourth right aortic arch and the associated part of the right dorsal aorta with suppression of the equivalent left vessels

C Abnormalities in pattern of subclavian and carotid arteries due to persistence of vessels normally obliterated and disappearance of those normally present (Fig 153)

« — D Coar ctation of the aorta In this condition there is stenosis of the aorta proximal to opposite or occasion^K 'jusTbelow the site of attachment of the hgamentum arteriosum An extensive collateral anastomosis is established between branches of the aorta above and below the stenosis In cases of complete airesia of the aorta m this condition the ductus arterosus usually remains patent

E Abnormabties of the coronary artenes which may anse from the pulmonary trunk or as a common trunk from one aortu, sinus

VI Great Veins of Thorax

A Persistent left superior vena cava draimng into the coronary smus B Faulty assimilation of the smus venosus into the rit,ht atrium v\ith the pulmonary veins possibly opening into it

•Anomalies of cardiac det elopment mav produce no chmeal manifestations (e g slight potency of the foramen ovale or complete situs imcfsus) or they may rtsuk m serious disability (c g stenoses of pulmonary or aortic orifices large septal deficiencies) or they may be mcom paiible w ith post natal life for more than a few hours or days (c g cor biloculare) A number



of congenital cardiac abnormalities may be well compensated for a number of years, but they often cause early death either by decompensation or by providing a suitable nidus for infective processes. Glassification of congenital heart disease is extremely difficult owing to its variable anatomical basis and to compensation For recent clinical classifications consult Abbott (1936), Taussig (1947) and Brown (1950)


Abbott, M E (1936) Atlas of Congenital Cardiac Diseases Am Heart Assoc, New York Amoroso, E C, Franklin, K J , and Prichard, M M L (1941) Observations on the cardio- vascular system and lungs of an African elephant foetus J Anat , Land , 76, loo-i 1 1 Barclay, A E , Barcroft, J , Barron, D H , and Franklin, K J (1939) A radiographic demonstration of the circulation through the heart in the adult and in the foetus, and the identification of the ductus arteriosus Brti J Radiol , 12, 505-517

Franklin, K J , and Prichard, M M L (1944) The Foetal Circulation and Cardiovascular System and

the Changes they undergo at Birth Blackwell, Oxford Barcroft, J (1936) Foetal circulation and respiration. Physiol Rev ,16, 103-128

(1946) Researches in Prenatal Life. Blackwell, Oxford

Barron, D H (1942) The sphincter of the ductus venosus Anat , 82, 398

(1944) The changes in the fetal circulation at birth Physiol Rev, 24, 277-295

Boyd, J D (1941) The nerve supply of the mammalian ductus arteriosus j Anat , Land, 75, 457-468. Brown, A J (1913) The development of the pulmonary vein in the domestic cat Anat Rec , 7, 299-329. Brown, J W (1950). Congenital Heart Disease Staples, London and New York

Butler, E G {1927) The relative role played by the embryonic veins in the development of the mammalian vena cava posterior Am J Anat , 39, 267-353

Congdon, E D (1922) Transformation of the aortic-arch system during the development of the human embryo Contrib Embryol , Carnegie Inst iVash., 14, 47-110 Davies, F , and MacConaill, M A (1937) Cor biloculare, with a note on the development of the pulmonar) veins J Anat , Land , 71, 437-446.

Davis, C L (1927) Devefopment of the human heart from Its first appearance to the stage found in embryos

of 20 paired somites Contrib Embryol , Carnegie Inst Wash , 19, 245-284 Evans, H M (1912) The Development of the Vascular System and Mall), 2 Lippincott, Philadelphia Flint, J M (1906) The development of the lungs Am J. Anat , 6, 1-137

Franklin, K J (1948) Cardiovascular studies Blackwell, Oxford ,

Goodrich, E S (1930) Studies on the Structure and Development of Vertebrates Macmillan, London Haselhorst, G., and Allmehng, A (1930) Withdrawal of blood from placenta at birth Geburtsh CynaK ,

98, 103-104

Hertig, A. T (1935) Angiogenesis in the early human chorion and in the primary placenta of the macaque monkey Contrib Embryol , Carnegie Inst Wash , 25, 37-82 His, W (1886) Beitrage zur Anatomic des menschlichen Herzens Leipzig . ,

(igoo) Lecithoblast und Angioblast der Wirbeltiere Abk d math-phys Klasse d Kyi Sachs ges a t >

26, 173-326

Hughes, A F W. (1943) The histogenesis of the arteries of the chick embryo J Anal , Land , 77, 2 J

Huntington, G S (1914) The development of the mammalian jugular lymphsac, of the tributary pri

ulnar lymphatic and of the thoracic ducts from the viewpoint of recent investigations 01 ver , lymphatic ontogeny, together with a consideration of the genetic relations of lymphatic and i vascular channels in the embryos of amniotes Am J , 16, 259-316 Kampmeier, O F (1912) The development of the thoracic duct m the pig Am J a,’

(1928) The genetic history of the valves of the lymphatic system of man Am J Anat, 4 , 4 3

Koch, E (1931) &e reflektorische Selbststeuerung des Kreislaufes Steinkopff, Dresden „,cnnrtion

Kramer, T. C (1942) The partitioning of the truncus and conus and the formation of the membran p

of the inter-ventricular septum in the human heart Am J Anat , 71, 343-37° Host .

Lewis, W. H (1931) Outgrowth of endothelium and capillaries in tissue culture Bull Johns p

McClure, C F , and Butler, E G (1925) The development of the vena cava inferior in man Am J d :

35, 331-383

In Manual of Human Embryology (Keibel

MTntyre, D (1926) of the heart Minot, C S (1912) Embrj'ologj


The development of the vascular system in the human embryo prior to the establish

^"he Or^’in of the AngfoblLt’’ Ind the Development of the Blood In Manual of Human, G J , A^deiofF.* W 8” (5S) of nerve o»ue .he med.a of .he

human ductus arteiiosus Odgers, P N B (i935) in the human heart J. . lond , 69, 412-422 _ , . land , 72,

(1938) The development of the pars membranacea septi in the human near . J >

• (19^39)^ The dcielopmcnt of the atrio-v'entricular v’alves in man J f ’ "^PoiUr^ Embryol.,

Padgct, Dorcas H. (1948). The development of the cranial arteries in the human e ry Carnegie Inst. Wash , 32, 205-261.

The formation oVthe venous valves, the foramen secundum and the septum secundum

CH\niR M


TiiF vertebrite urot,cninI s\stem includes ihc unttar} (cxcrcton) and tlie gemtal (rcproclucti\c) orgms The unmr> organs include paired c<crclor\ glands or kidness togctlicr uith associated cxcrctorj ducts The reproductive organs consist of paired ovaries or testes and their respective ducts which as will be seen dilTcr m origin in the two sexes

The urinar> and genital svstems are closch linked m their development and in the earlier stages of ontogenj and phjlogcn) their ducts open into a common ciidodcrmal cloaca, which is the'’dilated terminal part of the hmdgut (I ig 233) In the male a part of the s>a.tcm primaril) concerned with urinarj excretion is later connected to the testis so that the primitive iinnarj ducts become part of the definitive genital ducts Fveo in the adult human male the urinarv and genital svstems still use a common channel (the lovv£r part of the prosvatic the nvemhranous and the penile urethra) to discharge ^

their products to the exterior In the female the primilivc excretory duct undergoes marked retrogression and takes no pari in the formation of the functional reproductive system In this sex the functional reproductive iract is developetl from a pair of ducts not initially related to the excretory organs these ducts are called the faramtsonefhne (MdUnan) ducts In spile of the close relatioruhip m development of the unnary and genital organs,

It is convenient and indeed necessary for descriptive purposes to separate the accounts of the development of the two svstems


The nephric system of chordates is imivcnally rccognired as being of mesodermal origin • In an earlier chapter the intra embryonic mesoderm of each side was dcscril>cd as separating into a medial paraxial mass which Incomes segmented to form the somites a lateral plate which remains unsegmented and forms the lining of the coelom and a segmental junctional rCj^ion the intermediate mesoderm lying between and connecting these two parts 1 he intermediate mass for the greater part of its length gives rise to a Tu^rogemc cord from winch most of the excretory system develops

The vertebrate pronephros 15 essentially an embryonic structure which persists only in the adults of cy^lpstomcs and some tel^sts and di^oi The mesonephros becomes the functional kidney of most anamniotcs In amniotcs including mammals and man two provisional embryonic excretory organs the pronephros and mesonephros arc formed in succession the latter supplanting the former and being itself later replaced as

Pio 0 — Scl ernes to show stages in ihe evolution of the pronephros \ shows ilie primitive condition m V hich the nijococlc opens into ihc ncphrocoele In I! Ihe mvocoele is no longer connected to tl e nephro coele In Can int rnal and external glomerulus have developed ~

"e/fjon- lubules appear to be of ectodermal origin thus resembling the protonephrid a of annelids In spite of ihis origin the excretory mechanism of ihevi- ammiU





Fig. 229. — A semi-diagrammatic reconstruction of pronephros and pronephric duct in a 19somite human embryo (based on Watt, 1915) The degenerating cephalic pronephric tubules are represented m outline thence to the prone phnc duct. In the amniotes the myocoele does not communicate with the nephrocoele and the neph rost ome is transitory or, as in mammals, abse nt In the last-mentioned vertebrate class, including man, the nephrogenic cord appears as a solid mass of cells from which the excretory organs and their ducts are developed.

The mesonephros is developed from the nephrogenic cord caudal to the pronephros; its tubules, however, do not form a new longitudinal duct but join the existing pronephric duct which is now called the mesonephric {Wolffian) duct Further differences from the pronephros are the absence of nephrostomes and external glomeruli.

The metanephros, which is only found in rep^s, birds and mammals, develops m a yet more caudal' portion of the nephrogenic cord and Its tubules connect with a special duct, th^urefer, which arises as a diverticulum from the mesonephric

an excretory organ by the metanephros or permanent kidney * In general, then, the ontogenetic development of the excretory system follows its phylogenetic history

Each provisional or permanent kidney is an excretory organ composed of a varying number of tubules {pronephric, mesonephric or metanephric) which are joined to a longitudinal duct opening into the cloaca, f In lower vertebrates the intermediate mesoderm, m the region where the pronephros develops, forms, in each segment, a hollow stalk, the nephrotome, which for a time connects the myocoele (cavity of the somite) with the coelom (Fig. 228A), The opening from the somite to the nephrotomic cavity or nephrocoele, is soon obliterated, but thT opening, the nephrostome, from the nephrocoele into the coelom usually persists for some time (Fig. 228B). The lateral wall of the nephrocoele becomes evaginated to form a tubule which turns caudally and comes into contact with a similar tubule from the nephrotome immediately caudal to it (Fig 229); this is repeated in succeeding segments so that a longitudinal pronephric duct is laid down which grows caudally and eventually opens into the cloaca. < The medial wall of the nephrocoele becomes invagmated by a capillary loop to form an internal glomerulus. In many types a tran^nt external glomerulus is formed m the adjacent coel omic wall (Fig 22^). Obviously the nephrostome permits coelomic fluid to pass into the nephrocoele and




t ^








  • ^TRA ExfeRNAl.


Fig 230

u ...30 —A section, at the level of the i^h somite, through a

(after Heuser) to show the devebpment ol the pronephric region

X c 230

  • There is some reason for maintaining that the separation of pro-, meso-, meta-nephros is artificial

nephrogenic material arises from a single source and exhibits identical properties throughout, ana mer uniformity m the structure and function of the various parts of the system” (Fraser, 1950); , _r„ncDhric

t Waddington (1938) and O’Connor (1938) have shown experimentally in Amphibia that tne p 1 duct IS formed by a caudal growth of the pronephric rudiment Waddington suggests ^ onephros pronephros is non-functional physiologically it acts by way of the pronephric duct as an inducer 01 in



duct In the highest vertebrates these three nephnc s>stcms overlap each other in position and time of their development (Fig 238!


The pronephros is first found, in embryos ofeight_or nin e somites, as a solid mass of cells in the interval between the coelom anti the ventro lateral border of the somites vshere it causes a slight elevation on the surfate of the embryo ^ 230) The cephalic limit of the organ vanes

m different embryos owing to the fact that anteriorly it IS undei^oing degeneration before the more caudal iov « ^ part IS fontied It usually extends from the 4th to

Flo 23i-\schfma».c«pr„rma..onofthc thej^jthjamite that IS mainly in the future cervical stages in the dilTercntiation of the niesone rceion The pronephros has usually completely

chne tubules A— at the a mm stage degenerated m embryos of -t mm except for the

11— at the i mm stage C — at the 5 mm , , t ^ ^ ,

stage D— at the 10 mm stage external plomeruli which may persist until a much

later stage The solid pronephne mass becomes subdivided into a media! vesicular portion vvhich however never forms an infernal \x glomerulus and a 1 iteral tubular portion The tubules turn cau'd^ ^ has^ alreadv^en described to form a longitudinal pronephne duct which reaches the endodermal cloaca m embrvos of about 4 mm and soon communicates with it





The mesonephric tubules appear later than the pronephnc tubules, but befor e the latter have degenerated They arise from the caudal continuation of the nephrogenic cord The mesonephric part of the cord is never seen in its full extent for while it is growing at its caudal end It IS undergoing division at its cephalic end into a senes of spherical cell masses which develop into the mesonephric vesicles (Figs. 233, 234 and 242).

In an embryo of 23 somites the mesonephric vesicles are present in the thirteenth, fourteenth and fifteenth segments, 1 e , first, second and third thoracic segments and thus overlap the caudal extremity of the pronephros. By the 5 mm stage the mesonephros grows and differentiates in the more caudal portions of the nephrogenic cord, extending from the sixth cervical to the third















ARTERY HIND GUT (endoderm)

lumbar segment It now piojects as a swelling from the posterior coelomic wall and possesses a thick mesonephric mesentery (Fig 231) At first there is only one vesicle in each segment, but later more develop presumably either bv subdivision of, or budding from, the existing vesicles. The mesonephric vesicles, once formed, undergo a series of modifications (Fig 231) which proceed in a cianio-caudal direction They become pearshaped and the lateral narrow tubular part unites with they existing pronephnc duct (now called the mesonephric duct) The medial part of each mesonephric vesicle enlarges and Its wall becomes invaginated by blood capillaries to form an int ernal glome rulus The tubule^ then fbrms an “S” shaped loop, the ventral limb forms the BowmaiiisS-psule portion of the~nml {Malpighian) corpuscle, the intermediate hmb becomes thickened and the dorsal hmb forms the circling tubule.

Fig 233 — Schematic ventro-lateraLview of the developing urogenital becomes thickened and the i92Ta?d"smC n^'TSr^" dorsal hmb forms the co^ccting


When the mesonephros has reached its caudal limit at the 7 mm stage at least two-thir s of the tubules have undergone cranio-caudal degenerative changes, which are first seen 1 embryos of 5 mm By the 20 mm stage few intact excretory tubules are found, but som persist as late as the 40 mm stage (Bremer, 1916, Altschule, 1930). The degeneration, w m is partly in the nature of a dedifferentiation, results in the extrusion of the capillary tu t r ^ the glomerulus Remnants of a number of the caudal tubules persist and may e in to a c ramal, ep igeni tal part and a caudal, paragemtal part. In the epigenital portion ^ ^ of tubules varies from five to twelve and these, excluding the first two, form of the testis or come into'~c5ntact with the rete tissue (see later) in the ovary. 1 .epigenital tubules persist as the ductuli aberrantes supenores (Figs 244-247) Some o t le



par'»'-enita\ tubu\cs become separated from the mesonephne duct to form the t>aradtd\mts in the male and the paroophoron in the female Those which remain attached to the duct become the ductuli aherrantes infenores in^ach sex

Functional Activity of the Mesonephros OvMn" to the absence of an internal glomerulus the pronephros of man does, not function is m c\cretor\ organ There is no direct e\idence of the functional capabilities of the human mesonephros but its cMological appearances and the evidence denied from experiments on other mammals suggest that n docs eliminate urine Gersh (1937) has shown that the mesonephros of pouch iming opossums and cmbiyos of the cal rabbit and pig are able to eliminate fcrroc>anide and phenol red He found that the period of the cxcrctorj abihts of the mesonephros o\ erlappcd the initial metane

phric functional actii il\ Gersh s results shoued that the rate of urine formation b) the mesonephros is exlremel> slow which ma> be explained in part by the low embryonic blood pressure Bremer (igi6) suggested that the t\-pc of placcntaiion influences the size of the mesonephros and the degree of development of the allantois Fhus in the pi^ where the placenta is of the epithelio clional variety VMth consequent relativ e inefTiciency of Its permeability when tom pared with embryos with haemo chorial placcntaiion the mesonephros ami allantois are much larger than in man (Chapter \VI)

HUMAN METANEPHItOS The excretory part of the metanephros dev clops from the portion of the nephrogenic

cord {metantphne blastema) (Fig 236) caudal to the mesone phros Its collecting tubules

Fic 234 — Schrraai c ventro-lalpral view of the developing urogeniul S)item ofan 8 mm hutnanembr>o (Based on Kell> and Bumam 1922 and Shikinami 1926 )

develop from the ureteric out

growth which arises from the mesonephne duct close to its junction with the cloaca (F'g 234)

The Ureteric Bud At a stage between 4 and 5 mm a hollow outgrowth the ureteric bud arises from the postcro medial wall of the mesonephric duct near its junction with the cloaca (Fig 238) This bud grows dorsally and at the same time its origin migrates to the posterior and later to the postcro lateral wall of the mesonephric duct (Fig 23 j) , later it comes to be directed cramalwards as its duct (the ureter) continues to elongate This elon^ration is due to active cranial growth of the bud to growth at its site of ongin due to caudal mVabon of the cloaca and to interstitial growth Shortly after its appearance the cranial md of the ureteric bud enUrges and comes into contact with the metanephrogenic tissue (blastema) of the caudal one fourth of the nephrogeme cord (Fig 236) Further growth of the bud results










in its cranial portion and the blastema being displaced cranially dorsal to the caudal portion of the mesonephros (Figs. 232, 241 and 242). Here it is situated retroperitoneally but anterior to the umbilical artery.

The enlarged cranial end of the ureteric bud now changes its form, becomes marked off from Its stalk and subdivided into a cranial and a caudal portion, the two future major calyces. Each of the major calyces gives rise by subdivision to a secondary generation of branches and these in turn to tertiary, etc. (Fig. 235) until thirteen or even more generations of collecting tubules of different orders are formed (Huber, 1932). Collecting tubules continue to be formed

until the end of the 5th month of intra-uterine life Each major calyx and, in turn, each tubule has a cap of metanephric blastema which will undergo differentiation, as IS described later, to form the excretory part, glomeruli and convoluted tubules, of the kidney (Figs. 235 and 236}. The second generation of branches becomes enlarged and absorbs the branches of the third and fourth orders to form the minor calyces of the kidney, hence it is the tubules of the fifth order that open into the minor calyces m the adult The subsequent generations of the tubules become the definitive collecting tubules of the adult kidney.

Histogenesis of Metanephros. The metanephric hlastemal cap undergoes differentiation in the following manner. The solid mass of metanephric blastema related to the termination of each tubule becomes arranged in two layers (Fig 236). Part of this bilaminar mass separates to form a hollow vesicles the renal vesicle, while the remainder of the tissue becomes the cap of the next subdivision of the collecting tubules (Fig '235)The first vesicles are formed m embryos of 18-20 mm Each renal vesicle becomes elongated in much the same manner as the corresponding vesicle in the developing mesonephros The vesicle IS at first somewhat pear-shaped, the stem being directed towards the collecting tubue with which it effects a umon It then becomes “S” shaped and the lower limb of the becomes invaginated by blood vessels to form a renal corpuscle (glomerulus) ; both this an that portion ^vhlch is attached to the collecting tubule remain relatively fixed in position. Further growth of the parts between the fixed points will exaggerate the existing curvatures an^^

\i ill produce secondary ones A secondary curve appears in the middle of the upper curve the“S” loop and forms the distal convoluted tubule. Another secondary curve at the junc on





Fig 235. — A schematic representation of the stages in the development and differentiation of the metanephric tissue and collecting tubular systems (After Huber, 1932 )


of the nuddle end loner loops forms the fnximd ™ ciMd mbulr The tem-ttmng pottiom of the middle and tdjommg paru of the upper S curse genu tottards the future medulla of the kidnc) to form HenU s loop (Fig 233) tp.

Each full> formed unit of kidne) tissue xxhich has developed from a renal \«icle and to which Braus (1924) has given the name nephron includes a f,lofnerulus connected b> a neck to the Erst (proximan convoluted tubule sshich leads into the proximal rnedullan segment continuous with Hcnlc s loop, this leads into the ascending limb of the medullarx loop and is continuous h) a connectmi, piece, walh the second (distal) convoluted tubule the latter terminal portion of the nephron joins a coUccUng tubule derived from the ureteric bud The nephrons ate grouped to form lobules (Fig 268) which pcnist until full term but graduall) disappear m carK post natal life kampmeier (1926) has shown that in the metanephros the fir«  generation of vesicles is vcstibial and rarelv joins the collecting duct the second and third generations maj onl> join for a short tune (Fig 237) Vt a later period of dev clopment small detached parts of mctancphric tissue ma> produce vestigial tubules in the region of ihe renal

Fic 236 •— \ srciion of poriiort of ib^ difTerentiaiing mrUnrpnric blaitcmal cap and collecting tubules

Ftc 937 "Section of portion of the foetal Itdoei shot in^ the rones of growth of the glotnrruli (after Kampmeier 1936)

pelvis The renal vesicles maj in part fail to join the collecting tubules Such closed vesicles ma> secrete unne to form cjsts Marked degrees of this condition give rise to congenital polj^slic kidnry, minor degrees possibly accounting for -i large number of the isolaieti cvsis found in the adult kidney The met4nephros is ongmally at the level of the upper sacral segments

During ns development the metanephros undergoes a relauvc change of position usually called the ascent oflhekidncv This « the result partly of the cranial growth of the ureter and blastemal cap but is also in part due to the diminution of body curvature during develop ment (see Gruenwald 1943 for discussion) During ascent of the kidneys their intrinsic blood vessels receive their blood supply from lateral splanchmc stem arteries which arise from the aorta at increasingly higher levels until the definitive renal artery is reached Failure ol ascent results m a congenital pelue hdn^ Venrsttticx of blood supply from lower levels than normal gives rise to abertanl renal arteries Fusion of the lower poles of tHe two kidneys during this ascent results in the so called hmeshae ktdrey ^fultIplc ureters on one or both sides are probably the result of early separation of the uretenc bud into two or more nans Foetal lobulation may persist



Functional Activities of the Foetal Metanephros. Gersh (1937) has sho-wn that in the foetal rabbit, cat, opossum, embiyonic chick and in the pig the metanephros can function in the glomerular elimination of ferrocyanide and in the tubular elimination of phenol red. In the chick the foetal urine passes from the bladder into the allantoic sac where It is concentrated by water reabsorption The pouch-opossum voids its urine directly into the maternal pouch In the true mammals the urine eliminated by the metanephros passes fiom the bladder into the allantoic and/or ammotic sac, but instead of being copoentrated there it is reabsorbed Gersh considers that the metanephros, in foetal life, is so constituted structurally

that It must eliminate substances, but this elimination may not be an excretion m the true sense or essential to the life of the foetus That the foetus does not depend on the metanephros for the excretion of end products of nitrogenous metabolism is shown by the birth, at f^ll term, of apparently normal babies m whom the kidneys are absent Nevertheless, that urine is excreted in quantity by the foetal metanephroi is Idemonstrated m cases of atresia of the urethra In such abnormalities the bladder and ureters are greatly dilated and may even be ruptured (Wells and Bell, 1946) \







Cloaca ouct

bladdci I


As has been described elsewhere (page^ >. and 211) the caudal part of the hmdgut, which receives the allantois, is slightly dilated and may convemently be called the cloaca * It is separated from the exterior by the cloacal membrane As has already been described, mesoderm from the primitive streak passes around the lateral edges of the cloacal membrane to the base of the body stalk raising the surface ectoderm skirting the membrane into a genital fold on each side (Fig. loi) The shallow depres„ o A , Sion bounded by the genital folds is the external

"”devlLp™„. 5 rTron 1 K?mS ?„4 proMaeun Th.s of

metanephros and their ducts at about the mesoderm extends beyond the cloacal memoranc 5 mm stage (modified from Braus) In this 5y proliferation contributes to the estab rTO"llT*^ 3 T1 fi in nCTiiT'^*® 0/40—0^^ ^ . _ - « 1







fcivt lishment of the .nfra-umWtcal abdommal^.all .


nephros and derivatives in green, metanephros (Wyburn, 1 937)

m orange, metanephric duct solid blue and -pUp pvnanrlinp- cloaca IS ontmuous

endoderm yellow The paramesonephnc duct, , expanding Cloaca IS , the

which has not yet developed at this stage, is three enQoderrn3.1 tubes tne 5 j

indicated in later figures m solid red ^ , allantois and the tail gut At about the 4 mm

stage (Fig 233) it is joined on eadi-sidfe, at

approximately the junction of its middle and anterior thirds, by the pronephric (later mesonephric) duct. In embryos of about 5 mm. the urorectal septum arises in the angle the allantois and hmdgut. As has already been described (page 2 1 1) this septum grows cau and divides the cloaca into a smaller dorsal part, the pnr nitive rectum, and a larger yen_ part, the pri mitive u rogenital sinus In embryos of 6 mm. the urorectal septum has grou

  • Strictly speaking the term cloaca should be reserved for the dilated terminal part of the hmdgut aft

is joined by the mesonephric duct


down to tiic le\cl of tlic orifices of tlic mesonep hric ducU As the septum increases in depth the rectum becomes further separated from the primitiac uroqcmtal sinus so tiiat in embr>os ofO mm there is onI> a small communication, X\ic doaeal [>tissage betuecn them (Iig 234) At about the 16 mm stat,c the urorectal septum reaches and fuses s\ith the endoderm of the cloacal membrane (Fic, thereba complctcl) separating the urogenital sinus pait

of the cloaca from the rectal part The site ol the fusion of the urorectal septum uitli the cloacal membrane is tlic pri mitisc /irnneum The part of the cloacal membrane in front of the primitive perineum is called l^^^rosmlal membrane and that behind it the anal mem brane After Its complete separation from the rectum the pnmiliae urogenital sinus miT be subdivided into a part above the level of the openings of the mesonephric ducts called th e tesico urethral can al since It gives rise later to the bladder and

primitiv£_iii£thra and a part below this level vvhicli IS the de finitiie vro^emlal si nus

During tKT^ dev clopmcru ol the urorectal septum the cloacal membrane undergoes a reverse rotation so that the ectocfcrmal surface IS no longer directed towards the developing anterior abdominal wall but graduall) comes to f\ce caudalh and sliglith posteriori) icf figs 233 and 25G) 1 his growth change

facilitates the subdivision of the cloaca and u 1$ brought about maml) b> the development of the infra umbilical portion of the anterior abdominal wall and bv the rctro-,ression of the tail The mesoderm that passes round the cloacal membrane to the caudal attachment of the umbilical cord undergoes further prolifera tion and growth so forming a surface elevation the genital tubercle The further growth of this part of the abdominal wall progressive!) separates the attachment of the umbilical cord from the genual tubercle (cf figs 242 and •'561

The vesico urethral portion of the primitive urogenital sinus winch gives origin to the bladder and upper part of the urethra has the shape of an elongated cvlmder This c)lindcr IS slightl) flattened ventro dorsall) and is con „tinuous craniall) with the allantois Tlicrc is however no sharp line of demarcation between the apex of the future bladder and the allantois \Nith the growth of the infra umbilical abdomi

Fig 339 — \ Iranivrne section through the cranial part of the left developing mesonephros and gonad m a 14 mm human embr)o In the gonad the sex cords appear as darkly stained strands X c Co

nal ivall the bladder segment oP the aesico urethral canal increases ,n size The dcfinitiie urogenital sinus (I ^56) becomes Ilattencd from side to side and elongated t entro dorsalis At the same time the endoderroal (and perhaps ectodermal) cells of the urogenital membrane proliferate and extend into the urogemlal stuus so that tts casits becomes laruels obliterated by the resulting loosely arranged tissue ^


The development of the genital system is complex owing to the fact that its dilTerent portions arise from diverse primordia In addition the contributions from these primordia vary qualitatively and quantitatively in the two sexes primordia



In the earlier stages (up to 17 mm.) of development there is no indication as to the future sex of the embryo since the gonads are not yet identifiable as testes or ovaries. Genetically, however, the sex of the normal embryo is determined at the time of fertilization (Chapter II)’ the sex of the zygote depending on whether or not the X chromosome is present in the fertilizing sperm. The duct systems of the future gonads are also indistinguishable up to this stao-e and for some time later. They are the paired mesonephric (Wolffian) ducts which have already been described and the paired paramesonephric (Mullerian) ducts which develop later than, but in close relation to, the former (page 241). These pairs of ducts have quite different developmental fates in the male and female. The



mesonephric tubule






endocnnal conditions under which further differentiation occurs are discussed later.








Fig. 240 — Development of the ovary A = 1 1 mm stage B = 25 mm stage C = 50 mm. stage

The histologically recognisable prraiordia of the sex glands appear, m embryos of 4-5 mm C.R. length, as thickenings {genital ridges) of the coelomic epithelium on the medial aspect of the mesonephros (Figs. 207B and 233) immediately after the coelomic lining in this region has transformed itself into an epithelium (Gruenwald, 1942) When the genital thickenings differentiate in the coelomic epithelium the basement membrane separating the latter from the underlying mesenchyme disappears and cords of cells proliferate from the epithelium into the mesench yme (Figs 239 and 240). As is discussed later the primordial germ cells are now generally believed to migrate secondarily to the region of the genital ridges (page 238). The gonads, therefore, are derived from three different components, the primordial germ cells, the coelomic epithelium and the subjacent mesenchyme of a limited part of the mesonephric ridge (see Gillman, 1948)' Until the 17 mm stage the developmental changes in these ridges are indistinguishable in the two sexes. The cells form a condensation, the genital blastema, whic extends over about the middle two quarter 0 the medial aspect of the mesonephros. T e mesonephros is now projecting into the coelomic cavity, possessing a thick mesentery whic is

separated from the root of the gut mesentery by a medial coelomic bay and from the parie a coelomic epithelium by a lateral coelomic bay (Fig. 231). Since this mesentery suspends bo the mesonephros and the attached genital blastema, it is now called the urogenital mesentery. The mesentery, the mesonephros and the gonad together make up the urogenital fold.

In the course of subsequent development the urogenital fold undergoes uons (Figs 240 and 241) As the gonad increases in size, and projects from the medial of the common urogenital swelling, deep grooves appear on its lateral and medial partially separating it from the retrogressing mesonephros laterally and the adrenal dorso-medially. Deepening of these grooves results in the formation of a gonadal mes



(mesoianum or mesorchtum) and the urogenital mesentery becomes attenuated As the gonad IS related only to the intermediate portion of the mesonephros, the urogenital lold cranial and caudal to the gonad is less prominent and docs not shosv the pengonadal grooves (rig 2 )

The mesonephric part of the original urogemtal fold nou show s a \ entro lateral (tubal) porUon, containing the mesonephne and paramesonephne ducts, and a dorso medial part in which are situated the retrogressing mesonephric tubules (Fig 241)

The development of the suprarenal (adrenal) gland (see page 329) and metanephros and the grow th of the gonad cause the urogenital mesentery ongm illy ly mg parallel to the v ertebml column m the sagittal plane to be displaced laterally especially in its cramal portion (Figs 266 and 267) In the caudal tubal part of the urc^enital fold, the medial inchnauon of the para mesonephric and mesonephric ducts results in the fold approaching its fellow of the opposite side and eventually fusing with it

thereby forming in the coronal plane the UTogenilat septum which lies between the bladder anteriorly and the hindgut posteriorly (Figs 250 271 and 394) As the tubal portion of the urogenital fold passes the brim of the embryonic pelvis it IS joined to the anterior abdominal wall by a mesodermal thickening the tngui'iaf fold or plica inguiaa/is (Figs 241 266 and 267) in which the gubernaculum of the testis or ovary later develops


Testis At about the 13 mm stage (Fig 239) the gonadal blas^ma becomes subdivided into ^sex cords b v the development of .fihrfuis t issue

bundles The jcx c ords are first joined to the germinal epuhclTuin ^d may

the 25 mm stage (Fig 241) the development of a dense^fib rous lay er the tunica albuginea separates the sex cords completely from the germinal epithelium which can^ therefore* ^ longer contnbute to them La^ development results in absorption of the primordial germ cells into the sex cords

and in the extension of the latter into the region of the mesorchium where they form ^a n etwork the ilson 1926) The cords then become canalized to form the semimferous tubules the walls of which are formed by the susientacular (Sertoli) cells surroundin^tKe intercalated primordial germ cells Some of the s horter co rds do not become canalized andpossibly persistas some of the intcrstmal of the testts Most of the cells hots es er are dem ed from the mescti^Tiial cells of the stroma In foetal life the testicular inferstittai cells shoo marked acmat) The rete testis becomes canalized relatiicl, late (50-90 mm ) and bj further extension into the mesonephric stroma joins some of the mesonephric tubules Some authors (e n von

nVohrm'Ieo "" “ “"S™ The five to ttvelve meso

oefsm to foSt ih P«S' =30) which jotn the rete testis lose thetrjlomeruli but

persist to form the vasa elferentia which hnng the rete testis into communlMtion with the











mesonephnc duct (Fig 244) The vasa efferentia, therefore, include the whole metonepliric unit— glomerulus, tubule proper, and collecting tubule (Gillman, 1948). ^

Ovary. The sex cords form in the same manner as m the testis, but soon become broken up into isolated masses As, however, no definite tunica albuginea is formed, separation of the cords from the germinal epithelium is incomplete (Fig 240) Many investigators believe that this epithelium continues to contribute cells to the SfflLcorcls in smaller or largei numbers t r^u g lm ut foeta X h fe, and in post-natal life until the nmnopause A rete ovarii is also formed but IS never as well developed as the rete testis It may occasionally form an imperfect union

with the mesonephric tubules The small groups of cells resulting fiom the fragmentation of the sex coids become grouped to form the primordial ovarian follicles in which the primordial ova become encapsulated. It IS possible that the encapsulating cells derived from the sex cords become the pregranulosa cells (Chapter II). In contrast to the testis the coelomic epithelium continues to contribute cells to the ovarian sex cords for a long time and possibly into postnatal life The ovarian interstitial cells piobably arise from the stromal mesenchyme as may also the cells of the theca interna (Gillman, 1948).

Primordial Germ Cells.

Problems of major biological importance m the developmental histoiy of the gonads are the origin of the primordial germ cells and the relation of these cells to the definitive germ cells Many investigators of invertebrates and infra-mammahan vertebrates have demonstrated conclusively that theie is an early segregation, during development, of those cells which give rise to all the subsequent sex cells of the organism (Hegner, 1914, Bout oure, i 939 j Nieuwkoop, 1949) reptiles and birds the primordial germ cells arc first found m the extra-embryonic portion of the yolk sac endoderm Fiom here they pass, by active amoeboid migration, into the body of the embryo proper Swift (19U) thinks that in some birds they pass into the embryo largely by way of the blood stream and in late somite stages settle in the region of the germinal epithelium where they proliferate during subsequent development to form the forerunners of all ova or sperms

An early segregation of the primordial germ cells has been desciibed in mammals, but theie is still no generally accepted opinion on the time or site of segregation of such cells or on their relationship to the definitive germ cells. Several investigators (e.g , Fuss, 1912, Hamictt, 1935) have described primordial germ cells in early human embryos and have suggested ttia









primitive urogenital sinus


Fig 242 Schematic ventro-lateral view of the developing urogenital system of a 14 6 mm human embryo (Based on Kelly and Burnam, 1922, and Shikinami, 1926)



thcN take origin in the pre somite stage either from the cndodcrm or the overlyrng mesoderm in a restncted area of the >olk sac wall close to the allantoic dnerticulum and ater migrate through the mesenterv to the region of the gcmuna! epithelium or the gonadal blastema Rccentl> ^\ltsch^ (1948) has demonstrated the ongin of the primordial germ cells in the endo derm of the >oIk sac near the allantoic diverticulum m somite human embrvos He has traced their migration from the >ollc sac to the hindgut wall and thence along its mcsenter> to the gonadal ridge where the> are concentrated at the 8 mm stage The primordial germ cells thus come secondarily into relation with the other two components coelomic epithelium and

mcsench)-me of the gonad Other investigators however (Slieve 1927 Simkins 1928 and Swezy and Evans 1930) have denied that such primordial germ cells exist or if they do exist that they are concerned with the development of the definitive sex cells In the absence of experimental data it is impossible to resolve this dispute but the work on other animals suggests that in mammals too there may be precocious segregation of the cells which give origin to the future functional ova or sperms

Everett (1943 and 1945) has shown m the mouse that primordial germ cells are first found in the gut endoderm and later migrate to the genital ridge epithelium The ova which form m post embryome life are denved from these cells which enlarge and then migrate into ihe ovarian cortex IF genital ridge tissue before sex cells have developed m it is



the Mullerian tubercle (Fig, 253). Each paramesonephnc duct may now be subdivided (Fig 250) into a cranial vertical part, an intermediate horizontal part and a caudal vertical part. The former two parts become the uterine tube; the caudal part, as already stated, forms the utero-vaginal canal. The cranial point of fusion marks the future site of the fundus of the uterus. The utero-vaginal canal and cells derived from its lower end give rise to the epithelial lining of the uterus and to, at least (see later), that of the greater part of the vagina. Proliferation of the tip of the utero-vaginal canal results in the formation of a solid vaginal cord which progressively increases the distance between the utero-vaginal lumen and the urogemtal sinus. This distance is further increased, according to Koff (1933), by the appearance at the 63 mm. stage of bilateral posterior endodermal evaginations (“sino-vaginal bulbs”) from the urogemtal sinus (Fig. 252) close to the attachment of the mesonephric ducts. Koff is of the opinion that approximately the lower one-fifth of the vagina is derived from the sino-vaginal bulbs. By cellular proliferation these bulbs soon become solid and their development results in the disappearance of the Mullerian tubercle.* At the same time, that part of the urogenital sinus immediately cramal to the smo-vagmal bulbs becomes narrowed and elongated to form the female urethra, and the smo-vagmal bulbs themselves move caudally

Fig 249 — Schematic drawings of the development and fusion of the paramesonephnc ducts at different stages of development (after Koff, 1933)

as the caudal part of the definitive urogenital sinus elongates in the sagittal plane to form t e vestibule (Figs. 253 and 254). The sino-vaginal bulbs soon reach their maximum development and fuse with the caudal end of the vaginal cord forming the vaginal plate This plate later becomes canalized by the extension of the utero-vaginal canal from above, and by the brea mg down of the epithelium of the now fused smo-vagmal bulbs from beloiv. This process ^ completed until the 162 mm. stage. It must be stated that a number of investigators (Bloom e and Frazer, 1927; Hunter, 1930, and von Lippmann, 1939) consider the whole of the to be derived from the lower part of the mesodermal utero-vaginal canal and, therefore, to ^ exclusively of paramesonephnc origin. Abnormalities, however, appear to support the that the vagina is of composite origin (McKelvey and Baxter, 1 935 , and Monie and igar so , 1950) „

The future junction of the body and cervix of the uterus can be recognized at t e 40 m^^ stage (Fig 253) The uterine portion of the utero-vaginal canal is not complete y separ from the vaginal portion until the 150 mm stage A slight sagittal curve deve junction between the two parts of the future uterus, and a second and more pronounce

  • Mijsberg (1924) and Kemperman (1931) believe, however, that the sino-vaginal bulbs are d

the mesonephric ducts

urocenital system


bet\%een the cervix and the future vagina Throughout fofetal and carl> post natal life the cervical portion of the uterus is larger than its bod> The musculature of the female gcmtal tract IS derived from the mesenchyme surrounding the paramesonephnr ducts which becomes condensed earU m development to form a muscular blastema The fusion of the parameso nephne ducts to form the uterus the retrogression of the mesonephros and the descent of the uterine tube m association with that of the ovary result 10 the transformation of the urogcmtal mesentery into the corresponding broad ligament The utenne tube remains in the free edge of this ligament the ovary is now attached to its postenor surface and the retrogressing mesonephros and its ducts are contained withm the layers of the ligament

Usually the caudal portions of the mesonephne ducts lose their connection wvth the urogenital sinus and disappear or migrate cramally with the growth of the smo vaginal bulbs Several investigators (principally Mijsberg 1924) describe a contribution to the vagina from the mesonephric ducts Although this is unlikely Grucnwald (194O has shown that the close ness of the relationship of the mesonephric andparamesonephne ducts cm explain abnormalities of development in which the former ontsdenvativc theuretcr open into the vagina or uterus Abnormalities in the fusion of the caudal portions of the para mesonephric ducts result m the various anomalies of the uterus some of which are illustrated in

Fig 255

Hymen Accepting Koff s view that the lower part of the V agina develops from the canaliza tion of the smo vaginal bulbs then the hyanen is the partition which persists to a vary mg degree between the dilated canalized fused bulbs and the urogenital sinus proper (Fig 253C) The hymen is, therefore composed of an internal layer of vaginal epithelium and an external laver

of urogenital sinus cpithelmm (both derived from endoderm) and an intermediate layer of mesoderm Those who believe that most of the vagina is developed from the fused para mesonephric ducts contend that the upper surface of the hymen is covered with mesodermal 1,1 e utero vagina!) epithelium The development of the hymen is inseparable from that of the lovser part of the vagina and whatever mterpretution is accepted as to the development of the latter the oriPin of the hymen mu t be correlated accordingly

PARAMESONEPHRIC DUCTS IK THE MALE Lntil about the 27 mm stage the paramesonephne ducts in the male and female embryos are identical m structure and position Thereafter, m the male they show degenerative changes and lose their communications with the coelomic cavity^ The upper extremity of each duct persists to form the appendix testis (Iigs 54^-246) the remainder of the duct with the possible exception of its lower end completely disappears The available developmental evidence does not permit of a precise statement as to the fate of the lower terminal pan of the male paramesonephne duct It may give nse to the pnwtatic utricle (uterus masculimts) or the









Fig 251 — Photomicrograph of a sagittal section of the pelvic region of a 48 mm female human embryo X c 14

latter may be of composite origin, receiving a contribution of endoderm from the urogenital sinus as Koff has described for the female vagina. On the other hand, the caudal part of the

duct may disappear entuely (Vilas, 1933) the prostatic utricle arise solely from the urogenital sinus and represent the smo-vaginal bulbs Normally the prostatic utricle does not appear to possess a true uteiine component but in abnoimal development a completely formed diminutive uteius may be found and may even possess bilateral uterine tubes (see Young, 1937, for a review of genital abnormalities)


Although the sex of the individual is determined at fertilization sexual differences do not become manifest in human development until about the 17 mm. stage Further, the chromosomal control of sex may be modified by other factors. In the animal kingdom, generally, three factors are operative m sex determination, these are (i) genetic (chromosomal), (2) endocnnal (hormonal); and (3) general environmental.

Genetic Factors. As explained earlier the sex of the zygote is determined by the chromosomal content of the fertilizing sperm If the ovum receives an X chromosome m the sperm the chromosomal pattern of the zygote will be 23 pairs of autosomes and one pair of X sex chromosomes, i e., in normal development a genetic female will result.

If the fertilizing sperm possesses the Y chromosome the genetic sex of the zygote will be male (46-}-XY). Genetic analysis demonstrates that the X chromosomes are the actual agents which decide the sex, for the Y chromosome is genetically without significance in sex determination; indeed, in many animals the Y chromosome is absent The precise mechanism of action of the sex chromosomes, like that of all other chromosomes, is still uncertain, but it is generally accepted that the genes synthetize enzymes which control the differentiation of the tissues In sex determination the mechanism appears to involve a balance between the X chromosomes and the autosomes If a single X chromosome is present the “genic” balance between it and the autosomes results in conditions which produce a male embryo If two X chromosomes are present the balance is altered and the embryo will be female On this analysis the difference between male and female is quantitative rather than qualitative and if the balance is altered



b> ibe X chromosome boms weaker or ‘stronger, relative to t ic ^

imersex conditions mav arise Thee condiuons though rare m mammals are common m other animal groups epeciall) m the Insecta (Goldschmidt 1938)

Endocrinal Factors The influence of sex hormones m embr>onic development IS nou well established and m lower tjpes the sex of the individual ma> be modified or even reversed bv administration of suitable hormones when the embr>o is m the neuter condmon Hormonal influence on sex reversal is well known in cattle— in the so called /r« marlin condi tion (Lillie 1917) where a genetic female calf is a co twin with a male The former s pnmarv (chromosomal) sex is female (\X chromosomes) while that of its co twin is male (\i chromo somes) During development the placental circulations of the twins anastomose, ovung to the fusion of the chorions (9 ncfiorial/uston) at an earl> stage of dev elopment so ‘^at the embp onic sex hormones pass frcel> from one embryo to the other Since the testes dincrcntiate belore

Fig 33 — Schematic clra\ ings of the ticht half (seen from the medial aspect) of ihe terminal pari of the ietnale geniio urmar) i^stem and alimentary tract to show the development of the uterus vagina and ureihra (after Kotf) A — 37 mm human embryo xc 45 B — 106 mm human embryo c 4 3 C — 151 mm human embryo X c 3 3

the ov aries the male sex hormones arc produced earlier than the female hormones and b) passing into the circulation of the genotypic female calf influence her sexual differentiation m the male direction Hence her genital organs show many male features the ovaries m particular are inhibited and show testis like characters and do not produce ova so that at maturity such a female is sterile The sex reversal however is incomplete because the sex hormones of the testes are presumably not completely equivalent to those produced by the chromosomes m the genotypic male Moreover the cells of the free martins tissues are genotypically female and do not respond m the same manner as the tissues of the male The free martin condition is unknown in man for probably as the result of interstitial implantatiori early anastomoses of the chorionic vessels do not readily occur m dizygotic human twinning

The manner in which the male and female sex hormones influence sexual diflcremiation m embrvomc life is not known Presumably at the end of the neuter period of development the chromosomes exert an influence which causes the gonad to become testis or ovary the change














Fig 255 — ^Abnormal fusion oi paramesonephric ducts A —

uterus didelphys (complete duplication of uterus and vagina), B — uterus duplex, C— uterus subseptus




paramesonephric DUCTS (fused)

Fig 254 — Schematic ventro-lateral view of the developing urogenital system of a 50 mm human embryo

to testis occurring earlier in most species The differentiated gonads then elaborate “embryomc” sex hormones which model all the accessory sex organs (mesonephnc and paramesonephric ducts, rete tissue, mesonephric tubules, external genital rudiments, and the urogemtal sinus and its glands) according to one of two plans, male or female. On the above interpretation the development of accessory sex organs depends chiefly on the sex hormones (Witschi, 1939 ; Burns, 1945) a and h\ and Reynaud, 1942 ). There are those, however, who consider that the parameso nephric duct system continues to develop (in the female) or retrogress (m the male) by virtue of the genic constitution alone and independently of any endocrinal influence Moore (1947/ concludes that mtersexual conditions do not “rest upon a hormonal basis for their but when atypical reproductive structures are produced or retained from any cause, e will respond to sex hormones when these become available ”

In the later stages of pregnancy sex hormones of both foetus and mothi.r may pass placental membrane “barner,” but apparently not in sufficient quantity to effect mar e^^^ either mother or child It is possible that the maternal hormones have some foetus as is shown by the great growth of the cervix uteri of the female foeuis near and by secretion (ivitch’s milk) in the breasts of many males and females at birt . an excess of oestrogens in the blood of new-born female and male infants, whic is in hypertrophy of the vaginal epithelium in the former and in metaplasia o t e P _ epithelium m the latter. The oestrogenic excess and the associated epithelial c anges ’ some days after birth The ovaries of the new-born also show marked signs o

stimulation. mbryo

Environmental Factors. In mammals the environment of the deve is approximately constant and is unimportant in sex determination In certain ^ directly however, of which the gephyrean worm Bonellia is the classical example, enviro


determines the sex (Baltzer 1914) for in proximity to the female, the z>gotes all develop into males but when removed from the female they develop into females In lower forms eg Amphibia (Witschi 1929 and WiUicr, 1939 ), it is possible experimentally to alter the primordial germ cells in a given embryo so that they may form either ova or sperms


It has already been indicated that the point of entrance of the mesonephric ducts into the primitive urogenital sinus divides the latter into an upper and a lower portion Only the upper portion is concerned in the development of the bladder and its further growth and the separation of the ureter from the mesonephric duct must now be considered

FORMATION OF THE BLADDER AND THE PRIMITIVE URETHRA After the 5 mm stage when the ureteric bud has

appeared the portion of the mesonephric duct between the bud and the wall of the vesicourethral canal is the common excretory duct (Fig 238) The ultimate fate of this duct is intimately concerned with the further developmental history of the bladder and primitive urethra By grow th changes which are incompletely understood the common excretory duct undergoes changes as the result of which the ureter and meso nephric duct come to open separatelv into the vesico urethral canal The usual

explanation given is that the common excretory duct

becomes dilated and ab Fio ->^6 — A dra\ mg ©r a reconstruction of the degenerating mesonephros sorbed into the wall of the J^e meiane^rosa^ihe lermmal part oflhe alimenury tract m a 53 mm , human embryo ITic urogenital smus is completely separated from the

canal L tus process com hwuigut by tbe urorectal septum (after ShiVtinami) y c o mences at the 6 mm stage

and at about the 9 mm stage the ureters and mesonephric ducts open separately each uretenc opening being immediately cranio lateral to the opening of the corresponding mesonephric duct

As development proceeds the uretenc onfices move progressively cranially and laterally in relationship to the mesonephric openings which not onlv remain close together but also migrate caudally The movement of the uretenc openings may be due to the absorption of the ureters themsehes similar to the process that took place with the common excretory duct or it may be due to the migration of the uretenc attachments or to complicated growth processes such as Frazer (1933) has desenbed It is widelv accepted that the tissue in the posterior wall of the developing bladder and primitive urethra between the onfices of the ureters and mesonephne



ducts (in the adult male between the ureteric openings and common ejaculatory ducts) is of mesodermal original (i.e , from mesonephric duct).* With the lateral displacement of the ureteric orifices the area assumes a triangular shape and is the primitive vesical trigone (Fig, 243). By the 2 1 mm. stage the vesico-urethral canal shows a subdivision into a dilated upper portion, the bladder, and a relatively narrowed lower part, the primitive urethra (Fig, 256), The trigone IS now an equilateral triangle which extends from the ureteric orifices to the newly established internal urethral orifice, but it does not include all of the presumed mesodermal contribution to the urogenital sinus, some of this mesodermal contribution extends down the posterior ivall of the primitive urethra to the mesonephric orifices in the region of the Mullerian tubercle. Such an origin of the trigonal region distinct from that of the remainder of the bladder, though not universally accepted by embryologists, appears to be supported by adult diffeiences in these two regions Thus the trigone is more vascular, possesses a richer innervation, its mucosa IS more firmly bound down than in the remainder of the bladder, and it possesses a special trigonal muscle sheet which is, significantly, continuous with the ureteric musculatuie (Wesson, 1920). It must, however, be stated that the developmental changes in this region are not completely understood and the possibility that epithelium of urogenital sinus (i.e., endodermal) origin spreads on to the trigonal region after absorption of the common excretoiy duct has to be admitted (See page 253 for discussion of the embryological significance of the various

epithelia.) Further, unless theie IS medial migration of the mesonephric mesoderm during its absorption into the bladder, there should be a persistent vertical strip of endoderm in the midline of the trigone

The upper part of the bladder is continuous with the allantois which, in human development, undergoes early retrogressive changes normally resulting m the complete obliteration of its lumen. Its connective tissue persists to form the urachus which passes from the apex of the bladder to the umbilicus. Whether or not the allantoic endoderm contributes to the lining of the definitive bladder has not yet been decided Abnormalities in closure of the intra-embryomc portion of the allantoic lumen result in such conditions as

Fig 257 — Abnormalities in development of urachus A — patent urachus (vesical fistula), B — urachal sinus, C — urachal cyst

are illustrated m Fig. 257,

In later development the primitive urethra in the female forms most of the definitive urethra (Fig. 247) In the male, however, it forms only that part of the definitive uret ra extending from the internal urethral orifice to the entrance of the common ejaculatory tic (Fig. 246)


The fate of the definitive urogenital sinus differs in the two sexes and is intimately to the developmental history of the external gemtalia Already at the 16 mm. definitive urogemtal sinus is divided into an upper portion in the pelvis (pars pelma) tv ic widest in the coronal plane and a lower portion related to the base of the genita or p tubercle (pars phallica) elongated in the sagittal plane; the latter part is separate ro ectodermal cloaca by the urogenital membrane (Fig. 256).

  • Ghwalla (1927) doubts if the mesonephric duct contribution to the vesic(>ure ra ^

and he describes the complete closure of the ureter from the mesonephric duct by the ureter

which IS probably derived from the mesonephric duct A new opening between the lu u later develops above the original site of closure For discussion see Gyllensten, 1949



Pelvic Portion of the Definitive Urogenital Sinus In the male the pelvic portion of the sinus become:, the lower part of the prostatic urethra and the membranous urethra In the female it maj contribute slightl> to the lower end of the definitive urethra and also to the development of the lower one fifth of the vagina (Pig 253) The endoderm of this portion of the urogenital sinus and of the prtmitiv e urethra gw cs origin to the glandular rudiments of the prostate m the male and its lioroologue in the female (page 2^9)

Prostate Gland In the male At about the 55 mm stage (Johnson, 1920) a senes of solid buds arise from the endodermal part of the pnmiliv e urethra and from the adjacent upper pelvic portion of the definitive urogenital sinus (Pig 246) These buds grow into the dense surrounding mescnch>-mc which diflcrcntiatcs into the muscular and connective tissue of the gland The buds arise from all sides of the m«hra* both above and bclowl^vc po ition of the prostatic utricle and are arranged into five groups (Pig 2^8) anterior middle (postcro superior) posterior and two lateral (Lowslej 1912) The posterior lobe rudiment arising from the pars pelv ma of the urogenWal sinus develops a separate capsule and appears to repre sent a special functional part of the gland Tins lobe is rarclv involved in prostatic hvpertrophj

which chief!) involves the lateral and mi ddle lobes but is more frequenti) the seat of malignant changes than the other parts of the gland (^oung 1937)

In the female Solid epithelial buds anse from the definitive urethra and from the adjacent pelvic part of the definitive urogenital sinus in embrvos of 60 mm (Johnson i9'>o) these are the female homologuc of the prostate The buds ansing from the p npiitiye uret hr a for m the ure thral g lands whilst those ansing from the urogenital sinus form the p ara urethra l glands of Skene The two sets of glands together correspond to the entire glandular male piostate In some pseudohermaphroditc conditions the female para urethral glands maj undergo hypertroph) to form a Jemale prostate gland


In embryos m the indifiercnt neuter phase of sexual development the surface area around tlie external aspect of the cloacal membrane shows three small protuberances (Fig 259) In front between the anleiior margin of the membrane and the infra umbilical

It should be noted that if the posterior wall of the prosutic urethra arising from this portion are also mesodermal li is generallv accepted prostate « endodermal

IS of mesodermal origin the glands however that the whole glandular



abdominal wall, is the genital tubercle, and on either side, flanking the membrane, are the genital (future scrotal or labial) swellings. The ectodermal area between the swellings IS the shallow ectode rma l cloaca or proctodaeum. By the i6 mm, stage, when the uroratal septum has reached the cloacal membrane, the latter IS divided into a posterior part, the anal membrane, and an anterior part, the urogenital membrane. The anal membrane lies in the floor of the posterior part of the ectodermal cloaca, now called the anal pit. In later development the anal membrane breaks down so that continuity is established between the anal pit and the Fig. 260. Caudal appendage (“tail”) caudal (rectal) part of the hindgut The persisting

infant (Reproduced by the courtesy ectodermal wall of the anal pit together with the most of Mr P J Blaxiand, F R C S ) caudal portion of the endodermal rectum form the anal

canal round which the voluntary (Figs. 397 and 398) and involuntary sphincters are developed Failure of the anal membrane to rupture, or of the anal pit to develop, results in one or other of the forms of imperforate anus (Fig. 272) Rarely, the tail may persist and appear as an appendage caudal to the anal membrane (Fig. 260)

The urogenital membrane lies at the base of the anterior part of the ectodermal cloaca now called the urogenital sulcus As the phallic portion of the urogenital sinus elongates in the sagittal plane it encroaches on, or is drawn into, the under surface of the genital tubercle At the same time the endodermal lining of the urogenital membrane proliferates actively, 'especially in its anterior part, and the cavity of the phallic portion of the sinus is more or less obliteiated. The proliferation m the part of the sinus related to the genital tubercle forms a solid urethral plate of epithelial cells Shortly after the 16 mm. stage the posterior part of the urogenital membrane breaks down and a communication, the primitive urogenital orifice, is established between the phallic portion of the urogenital sinus and the urogemtal sulcus The anterior portion of the latter extends on to the ventral aspect of the genital tubercle as a urethral







Fig. 261. — Development of the external genitalia B — 21 mm X c. 15 5, C — 58 mm X c 7

in the male. A — 14 5 ntm X c ^ (After Otis 1906, and bpaulding, 19

15 .

urogemtai. s^sn^^

25 '

^roo\c on ihe surface of the urethral plate I* >s important to renhre that this urethral groo\c ts continuous with the urogenital orifice Tlie further development of this region fna> best be considered b\ separate descriptions for the male and female

Male With further crowth the j,cnital tulx-rclc Incomes elongated and is transformed into the calindncal phallus (1 ic aGt) At tlie same time the genital s\\elhnt,5 which can now lie railed scrotal liccomr more dehnite The urethral groove extends forwards on to the ventral aspect of the phallus but does not <pvitc teach to the tip vvhcrc a small ectoslcrmal tag is freqoentU attached The primitive urogenital orifice ami the urethral groove arc liounded either side bv urflhral folds

i — \nienor vif'v of a iprtimrit offciopia vciicae

Fio 3G3 — Mnortnal devdopment of penis a It C an 1 D t) ow difTcrent vaneucs of hvpospadiai ai tern in turfaee view \ fl C and D are the rofrnpondinf laCjiUal s ciinni

which liecome mort distinct At about the mm stage the male genitalia lake on approximatrlv ihcir final form as the result of fusion of the urethral folds m the middle line from the posterior ctlgc of the iimgcmtal orifice towards the tip of the phallus fonning a median raphe oscr the resulting /u6ufar uKthra As the edges of the urethral folds fuse progtcssivel\ from liehind forwards the primitive urogenital onfice ts thus graduallv reduced m sire and earned as an irreguhrlv slnpetl opening on to the under surface of the phallus (1 ig 261) vvhere it lies Ivlow the Urethral plate The glans /fms has now liecome defined b> the develop* ment of 1 circular coronan sulcus around the distal part of the phallus The urclhnl groove and folds do not extend licvond the coionarv sulcus and vvhen the folds have liecomc complete!) united a closetl pmit urtilira is formed A cord of ectmlermal epithelial cells grows through the glans to reach the distal cxtrtmil) of the closed urethra and later liecnmes canalized to form the tcnmnal (glandular) portion of the urethra If the process of fusion of the urethral folds does not extend the whole length of the phallus an abnormal condition (h/ospadias) m which the definitive urethral orifice IS on the ventral (under) surface of the phallus results (Fig 2C3) On this mtcrpretation of development the penile urethra arises as the result of fusion of the urethral folds ami is largeU 01 cndodcrmal original though there may l)C some ectmlcrm in its floor

The bulbo urethral glands arise from a portion of the penile urethra of presumed cndodcrmal origin and they loo are regarded as endodcrmal derivatives After the penile urethra has been est ibhshcd lU posterior extremity sldates to form a bulb and later connective tissue surrounding the urethra becomes condensed to form the corpus ffltfrnoium urethrae m vvhich numerous wide and convoluted blood vessels showing arteriovenous anastomoses develop Small glands (ofLiltre) develop m the penile urethral wall At first the glans penis is naked but at about the 70 mm stage (Hunter, 1935) a reduplication of the ectoderm, the prepuce comes to overhc Jj and Will eventually cover n completely This reduplication is adherent by epithelial fusion of the opposed layers until late in foetal hfe

Fir 264 — Abnormal dc vclopmcniof penu and bladder A Fpispadias ft Sasjiiiaf section of ihc pelvis in epispadias C Sacitial section of pcUis in ettopia vcsicae (ex Iroversion of bladder)



The description given above is that generally accepted but the manner ol development of the penile urethra and bulbo-urethral glands in the male is still controversial. Barnstein and Mossman (1938) have studied the development of these structures in the squirrel and shoiv that the urethral plate starts as an ingrowth of ectoderm. This line of ingrowth extends distally along the ventral surface of the phallus and results in the formation of an ectodermal urethral groove As the plate extends distally its older portion thickens and becomes separated from the surface ectoderm posterior to the groove This results m a distal migration of thegioove, leaving behind it, and connected with it, a thickened urethral cord of ectoderm leading deep through the perineal tissues to its junction with the phallic portion of the urogenital sinus This cord becomes canalized from the urogenital sinus distally to form the penile urethra The lumen reaches the surface only after the urethral groove and plate have reached the tip of the phallus and the plate has been completely transformed into a cord According to these observations, the whole penile urethra is ectodermal with the possible exception of a little endoderm at its proximal end where the first anlage of the urethral plate had its connexion with the urogenital sinus. The bulbo-urethral glands develop early as diverticula of the proximal



Fig 265 — Differentiation of the external genitalia of the female A — 15 mm X c I 5 )

B — 23 mm X c 15, C — 65 mm X c 3 (After Spaulding, 1921, and Fischel, 1929)

end of the thickened portion of the urethral plate and are, therefore, ectodermal m The median raphe of the penis, scrotum and perineum is probably not the line of fusion 0 urethral folds but merely a remnant of the line where active ingrowth of the ectoderm ga rise to the urethral plate , -g

In addition to the abnormality known as hypospadias, which results from non c 0 or partial closure of the urethral groove, a condition called epispadias is occasionally ^

it the dorsal wall of the urethra is partially or completely absent (Fig. 264). This a is due to a failure in the development of the mfra-umbilical mesoderm and, in (.j^g

results in ectopia veswae (Figs 262 and 263) m which the bladder mucosa is expose

anterior abdominal wall. ternal

Female. Up to approximately the 25 mm stage (Fig 265) the appearances genitalia of the female resemble very closely those of the male except that the uret ra is shorter. Wilson (1926), however, found that only after the 50 mm. stage cou ^ubeiclc

determined from external characters without error. Soon after the gen™,.

becomes bent caudally and can be recogmzed as the clitoris It is not ^i^ent of

the urethral plate to any marked extent and consequently there is no fema e eq



ibe pemlc portion of the male urethra The ^mtal or Jabial swelli ng? - gr . o n together m front of the anus and posterior to the urogenital onfice to form the.) 30 sjenor c^missure The lateral portions of the labial spellings then enlarge to form ihitjab\ajriapra The urethral lold^ dankm the urogenital orifice do not fuse but persist as the labia minora , thus the phallic portion and the <Teater part of the pehic portion of the un^enital sinus are esposed on the surface as the sestibule The \agina and urethra open scparatelv into this the former onlv partially because of the presence of the h>-men \ pair of glands prcsumabH of endodermal ongin arise from the \cstibule These are the ^eater leslihular {Bartholin s) glands the female

homologues of the bulbo u rethra l glands Small glands (lesser vestibular) develop m the anterior part of th^ vestibule and are interpreted b) John son (1920) as representing the glands of Litire of the male The precise junc tion between the ecto derm md endoderm is not identifiable m the later stages of develop ment but IS generally taken to be at the free edges o f the labiaminor a

EPITHZLIA IN THE UROGENITAL SINUS The epithelium lining the difTercnt portions of the genital and urinar> tracts IS of diverse origin, that of the mesonephric and paramesonephric ducts is mesodermal, that of the bladder and a large part of the urethra IS endodermal with probably some meso dermal contribution in the trigonal region while

that of the penile urethra is at least m part ecto dermal Nevertheless the epithelia limng the

Fic »66 — Adi section of the po tcrior abdominal V all in a 6 mm humm embryo to show the relationships of ihc gemto-unnar^ apparatus and Its associated ducts The lines of peritoneal reflection are also shown

ducts of diverse origin are frequently histologically indistinguishable There can be little doubt that there is some intermingling t>f the epithelia in the linings of the various urogenital organs the vagina for example probably derives a large part of its limng from the definitive urogenital sinus which is in its turn invaded by epithelium from the ectodermal proctodaeum Occasionally patches of specific epithchum appear at a distance from their source a condition w hith may be due to early migration forming embry omc rests or mav result from an actual change m nature of the cells (metaplasia) It frequently appean in conditions of abnonnal hormonal stimulation The response of the different tissues to hormonal





stimulation (e g., by oestrogens) only in part reflects their embryological origin (for details see Zuckerman, 1940, and Burns, 1942).


The testis and ovary come, in late foetal life, to occupy a position different from that in which they are found in the embryo The change in position of the testis is more marked than that of the ovary involving, as it does, its passage from the abdominal cavity through the abdominal wall into the scrotum which develops by the enlargement of the genital fold The

descent of the gonads may be considered in two stages —

(a) That common to testis and ovary and closely related to changes in the mesonephros.

(b) That peculiar to the testis, its passagefrom an intra-abdominal to an extra-abdominal position.

Both of these stages

are usually called “descent,” but Felix (19*2) and others would restrict the term to the passage of the testis from the intra-abdominal position as they believe that tiue descent plays only a minor part in the ear ler


Testis. In embryos of 26 mm the gonad (Fig 266) is attached to the posterior abdominal wall by the gemtal and common urogeni a mesenteries The crania extremity of the gona IS attached to the atro

Fig 267 — A dissection of the posterior abdominal wall in a 70 mm male human embryo showing the position of the testis On the right side the peritoneum has been removed from the front of the testis to show the vas deferens and epididymis The lines of peritoneal reflection are indicated

phying mesonephros by a suspensory ligament which later disappears ‘^^^^^^p^^enTous

of the gonad, which does not pass into the true pelvis, is continued by a ig band into the urogemtal mesentery. The latter, - at this level, shows a swe projects towards and fuses with a corresponding swellings



the crista inguinaliS:

piujci-i-a tiiiia iu»cs Wllll a COrrCSpuIlUIllg riic w... o , mPUlWl

deep aspect of the anterior abdominal wall. As the result of this fusion a ban , formed. fold (Fig. 241), which reaches from the urogenital fold to the anterior abdomina band, the The mesenchymie in the inguinal fold becomes condensed to form a developing

gubemaculum, which passes obliquely from the lower pole of the testis, throug ^jgsue of the muscular layers of the anterior abdominal wall, to terminate in the subcutaneou^^ saphenous scrotal swelling. Additional terminal strands extend to adjacent regions (near



opcnmg root of penib abo\e the inguinal ligament the perineum and pubic spine) The lo%ver pole of the testis is apparently held m position by the gubernaculum With the degeneration of the mesonephros and possibly also the degeneration of the cranial part of the testis itself the latter gradually comes to he at a relatively lower level on the posterior abdominal wall This change in position is accentuated by differential growth of the posterior abdominal wall and related structures During this stage of 'descent the suspensory ligament disappears and the mesorchium and urogenital mesentery become very thinned, the original blood supply from the aorta being however, still retained (Fig 267) By the third month of foetal life

(70 mm ) the testis is lying retropentoncally in the false pelvis near (he an^le between the antenor and posterior abdominal walls Just in front of its lower pole the peritoneum herniates as a diverti culum the proussus laginahs along the ventral aspect of the gubernaculum even tually reaching the scrotal sac through the muscle layers of the anterior abdominal wall The region around the processus vagmahs and guber naculum ma\ now be recognized as the ingu inal canal The testis remains at the abdomi nal end of the inguinal canal until the seventh month of foetal life During the seventh month the testis passes through the inguinal

canal lying behind but in aginating the processus \ agmalis Normally itreaches the

Fig '’68- — \ dissection ofamalehiinian foetus near Tull term to show the descent of the testis and the formation of the tunica \ a?inalis The testis on the left side of the specimen is sbov n at a later stage of descent than that on the right

scrotal sac by the end of the eighth month (Fig 268) The descent of the testis is accompamed by a corresponding shortening of the gubernaculum but the role of the latter m the mechanism of the descent still controversial The degenerating mesonephros and the mesonephric duct (now called the vas deferens) accompany the tcstis durin^, its descent The lower portion of the processus vaginalis persists as the luntea vaginalis lestis but the upper part normally becomes obliterated by apposition of its walls at or shortly after birth (Mitchell •939) If It remains patent a congenital inguinal hernia usually results Variations in the degree of the persistence of the processus vaginalis are shown in Frg 269 For a discussion of the morphological aspects of the descent of the testis see Wvndhain (' 943 ) ^



Abnormalities in the Descent of the Testis. The testes may be retained within the abdomen (cryptorchism) or may only partially descend, i.e,, come to he at the abdominal end of the inguinal canal or at the pubic spine, or a testis may descend but occupy an abnormal location (ectopia testis) (Fig. 270) These abnormalities are more common on the right side. Hinman (1935) states that one in every 25-30 boys under fourteen years of age and one in every 250 men over twenty-one years of age have imperfectly descended testes. Of these approximately 85 per cent eventually descend into the scrotum Failure to descend may be due to conditions connected with the mesorchium or gubernaculum or may be due to abnormalities of the testis itself The presence of a congenital inguinal hernia or of abnormalities in the tunica vaginahs often accompanies failure of descent (Fig 269).

The biological reason for the descent of the testes is unknown It has been shown, hoivever, that normal spermatogenesis does not occur m a human testis retained m the abdominal cavity. It IS thought that the mtra-abdominal temperature is not the optimum for the production of mature spermatozoa (Moore, 1926). In the different mammalian groups there is some coirelation between body temperatures and the descent of the testis (Wislocki, 1933) In general, animals with low body temperatures retain the testes permanently within the abdomen ivhereas those with higher temperatures show periodic, or permanent, descent

” i


Fio 270 — Diagrams lo show incomplete descent and ab normal location of the tes tis A — abdominal testis B — superficial inguinal tes tis C — external abdominal ring testis D — perineal testis E — crural testis F — abdominal rings G— pubopenilc testis



The sex of the human embryo js determined at fertilization and depends on tvhether or not the sperm which fertilized the ovum possessed an \ chromosome This interpretation is strongly supported by the phenomena of sex linked inhentance and by the identity of sex in monozygotic (monovular) mins Certain abnormalities however show that the difference between male and female is not an absolute one and there is a voluminous literature (\oung 1937) on inlmex (AermaphrodiU) conditions These condiuons are to be explained by abnormal genu balances between the \ chromosomes and autosomes In the classical a hermaphrodite is an md.t.dual poKessing the gonads and eiitertial_genitalia of both sexes and capable of living the full reproductive life of both m^e and female There is no valid endenee that sueh a human indiv tduaritas ever existed The

rb >'>' '"""•m can be

classified as true or as pseudohermaphroditism

sexesI”p'e""”eTxtm^Vev’‘'h “ *e' "h'fh ihc gonads of both

. . ^ characters may be m^e female or intermediate It may Be

4 n

otteto r;nd"'o°'“' ■' 'oon’il'no'i one organ, a so called

ovotestis ) and one gonad on the other

W Bilateral -Both ovary and testis on each side or bilateral ovotestis

True hermaphroditism is ver\ rare and in the human theic are only twenty proven ca s (\oung 1937)

Pseudohermaphroditisra This IS a condition which IS always congenital m •ngin the individual possess in ..onads of one sex whilst the external genitalia and often the secondary sexual characteristics are of the opposite sex or approximate to them In mam such cases the sex has been wrongly interpreted at birth and the true sex of the individual is onlv manifest at puberty In other cases the true sex of the individual can only be determined by an examinaoi^ans i( 15 estimated stat l internal sexual

in 1000 persons it mu u ^ some d^ree of pseudohermaphroditism occurs m one

W External

glands and ,, in which the external genitals are male and the sex

<he mtemal genital, are female



(b) External female hermaphroditism m which the external genitals are female and the sex glands and internal genitals male

(c) Internal male hermaphroditism in which m addition to testis and male external genitals a uterus, uterine tubes and vagina are present

{d) Internal female hermaphroditism m which in addition to ovaries and female external gemtals there are male and female internal sexual canals, 1 e , vas deferens and uterus.

(e) Complete male hermaphroditism m which the external genitals and other accessory sex organs are female but the sex glands are male.

(/) Complete female hermaphroditism m which the external genitals and other accessory sex organs are male but the sex glands are female

(g) Various combinations of the above conditions


(a) The metanephnc tissue, of each side may become completely united to form a single mass resulting in fused kidney, or at the caudal extremities to form a horse-shoe kidney.

(b) The metanephnc tissue may fail to develop and hence there will be unilateral or bilateral absence of the kidney.

(c) The ureters may be duplicated owing to the development of more than one ureteric bud or the division of the original single bud.

(d) Congenital polycystic kidney and solitary cysts of the kidney are described on page 233 The cysts arise from renal vesicles which have failed to fuse with connecting tubules.

2. Gonads and Genital Ducts.

(a) The different types of hermaphroditism are described on page 257

(b) The testis or ovary may be atrophic or absent on one or both sides due to failure of the gonad to deve op

(c) Supernumerary testes or ovaries may be duplication of one or both of the gonadal masses du g development

IG 272 — Abnormal development of urogenital pfjnipcr A — The anal membrane has persisted to give rise o

forate anus B — The rectum has failed to P rise to

rectal septum has failed to complete its yagma is incom

persistent cloaca or recto-urethral fistula in between

pletely separated from the gut so that a comm fistula

nvo structures persists, giving rise to a recto-vaginal fistula




Indtffertfil stag*


Probably tiisapprars


Probably disappean


Genital gland


Seminifetous tubules

Germinal cords

Pfluger s lubes

D sappear ^

Ductuh aber \ cephalic

ranies superiores /

EfTerent ducts of \ inter

epididymis / mediate

Ductuliis aberrant "I

inferior and ^ caudal

paradid mis J

^ upper 1

' Collecting

I middle

tubules of

• lov er

J mesonephros


middle J

lovser ■>


^ I


V Disappear

' cephalic C Duetuli

X aberrantes

I b superiores

I tnief f Tubules ol

mediate \ epoophoron

r Ductulus

I aberrans

caudal inferior and

I tubules cf

1. paroophoron

Duel of epididsms \as deferens 1 appendix of epididymis common j e^aculatorv duct seminal vesicle I ingone of bladder |

Mesonephric duct (Uolllian duct) initially pronephric duct

Straight lube of epoophoron and Gartner sduct tngoneofbladder

Appendix testis

’’ Part of utnculus prostaticus ' (uterus masculinus or vagina masculina

Paramesonephne duct (Mullerian duct)

Uterine tubes uterus upper four fifths of vagina

’ Linculus prostaticus

Sino vaginal bulb from urogenital sinus

Lower one fifth ofvagina

Bladder and prosiaiic urethra above the orifices of the ejaculatory ducts (except trigonal region) dehnicive urogenital sinus

Pnmiiivc urogenital sinus

Bladder and greater part of urethra (except trigonal region) definitive urogenital Sinus

Frostatic part of urethra belo v (he

0 ifices of the ejaculatory ducts membranous uiethra penile uie thra (except urethra of glands)

Definiiive urogenital sinus (lower pari of primitive urogmiUl sinus after the vesicivureihral canal has separated from it)

Vestibule and (*) lov cr part of urethra

Prostate gland

Urethral glands and glands of pars pelvina of urogeiutal sinus

Urethral glands and paraurethral glands (Skene s tubules)

Penile urethral glands (glands of ' Littti) bulbo urethral (Cowper s) glands

Glands of pars phallica of uro

Lesser vestibular glands greater vestibular (Bartholin s) glands

Gians pen s

Gians of phallus

1 Gians clitoridis

( ’) Floor of penile urethra

Lips of urethral groove

Labia minora


Genital sv citing

Labia majora

Gubernaculum testis


Ligamentofovary round ligament of uterus

Vo established homologue

Junction of siiu>.saginal bulbs and urogenital sinus




{d) Abnormal descent of the testis and cryptorchism are described on page 256

(e) Abnormal fusion of the paramesonephric ducts may give rise to double vagina, uterus didelphys, uterus duplex or uterus subseptus (Fig. 255). Absence of one paramesonephric duct results in uterus unicornis.

3. Cloacal Region and Parts Derived from it.

(a) The urorectal septum may fail to develop, resulting m persistent cloaca (Fig 272)

{b) Mesoderm may fail to migrate from the posterior part of the primitive streak close to the attachment of the allantois between the ectoderm and endoderm m the future suprapubic region so that these two layers coming into contact fuse, later break down, and give rise to ectopia vesicae (Figs 262 and 264).

(c) Part of the intra-embryomc portion of the allantois may persist and give rise to a urachal fistula or urachal cysts (Fig. 257).

{d) Failure of rupture of the anal membrane results in imperforate anus (Fig. 272)

(e) Failure of establishment of a commumcation between vaginal cavity and urogenital sinus results m imperforate hymen which at puberty prevents discharge of menstrual blood {cryptomenorrhoea ) .

4. External Genitalia (see also pseudohermaphroditism, page 257)


(a) The phallic tubercle may become divided into two giving rise to double or bifid penis.

(b) The urethra of the glans penis may fail to become canalized and the terminal part of the urethral folds may fail to fuse. Minor degrees of the latter give rise to hypospadtasi extreme degrees to congenital perineal urethral fistula or complete hypospadias

(c) Rarely, a urethral groove is found in the upper surface of the penis, this condition IS called epispadias and is often associated with ectopia vesicae (Fig. 264).


Congenital hypertrophy of the clitoris or labia minora, or both, may result from stimulation of the foetal genital organs by maternal oestrogens which have passed the placental barrier in excessive amounts


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"nd®i"dL„VkSl;’ iT'zrii



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Iv man and other %ertcbrates the ncraous s>stcm and the neuro epithelium of the organs of special sense are derued from the cmbr>omc ectoderm * The central ner\ous s\stem— brain and spinal cord— takes ongin from an elongated area of ectoderm the neural plate %\hich is situated m the avial region of the embr>o m front of Hensen s node and the pnmitive streak The peripheral nervous s>stem arises from cells which are denved m part from the neural plate in part from a specialized band of ectoderm the neural crest which flanks each lateral margin ofthc neural plate and to a minor extent m the head region from localized ectodermal thickenings called placodes

ESTABLISHMENT OF NEURAL TUBE The fundamental form of the \crtcbrate central nervous s>stem is a hollow tube At an early stage as the result of diflercntial growth and expansion of its walls this simple neural tube shows a division into a c>lindrical and elongated caudal portion which becomes the spinal cord and a much more specialized shorter and broader cephahe portion which becomes the brain The central ta\at> of the developing brain aoon shows three segmentallv arranged dilatations separated b> two annular constrictions These dilatations are the pnmarv brain

vesicles Their cavities become the subsequent cerebral ventncles and aqueduct Their

walls represent the three principal subdivisions of the vertebrate bnin The rostral dilatation IS called the forebrain vesicle and its walls form

the troseneebkalon The intermediate dilatation tm o sntricle

1 11 1 n /■ . CAM KA TER ^AL S

IS the midbrain V estcle its walls form the mrsrn ’ latera l ent

ctpkalon The caudal dilatation n the hindbrain "" ~

vesicle and its walls form the rhombencephalon /e ^

The mesencephalon shows no fundamental fS /f^ (I

change in subsequent development but each of /£ U

the other two vesicles undergoes marked modifi // ju p ‘ \ i\

cation The front part of the prosencephalon I \ j j ln\(l t 1

gives ongin on each side to a lateral oulgrovwh \ \ / / V/

the telencephalic vesicle (Fig 273) In 'sub

sequent development the walh of P^d eni.epmai.on-^

become the cerebral hemisphere The wall of n ^ mesencermalon*" aK

the caudal part of the original prosencephalon \r\^

IS novv called the i/icnr<’/A<j/on^^rom this portion Jy isthmus*" 1 \ J

of the brain in all vertebrates an optic evagma yX [/ \ * r

tion grows out on each side to form the neural Y| [j metehceph loh \ s / /

components of the e)e ball and the o^c nerve ^1? If

The rhombencephalon is subdivided m later 11 « a |li( b

development into a more rostra l metence^ ialon mtelenlephalon

continuous through a narrowed tsthmu> witb' ourmvemtrcle

the mesencephalon and a more c^dal myelfn draviongi to show two stag« 

I f 1 « m oevciopnieni of the rcmonal difTrrentiation

«/-Aj/on continuous With the spinal cord {Fig ttfihebram ^ ai auicrenuauon

273) The metencephalon giv« origin to the

I« IS possible that some of the taste buds are of endodermal onpn \an CatSDeobaut fiQiai hat P«««ies that conmbute to th^nervoJ St nfof






pons and the cere bell um whereas, the myelencephalon develops into the medu lla oblongata. In the higher vertebrates the boundary between spinaljord and medulla is not sharply de fined as the upper segments of the spin al c ord are assimilated to a v ariable exte nt into this part of the brain. The cav ities of the telencephahc vesicles become the la teral ventricles, _That__of the original prosencephalon persists as the Illrd ventricle. The IVth ventricle represents the cavity of the orig'inal_j:hombjencephalon^(Fig

273) In the human embryo the neural plate firs t appears, in the late prespmite staged — as a" thickened ectodermal area which becomes distinguishable by an increase in the height of its constituent cells. The plate overlies the notochordal process and the medial edge of the paraxial mesoderm; anteriorly it terminates at the same level as the notochordal plate, 1 e., at the posterior edge of the future buccopharyngeal membrane The neural plate soon becomes depressed axially to form a shallow longitudina neural groove (Figs 45 and 49 ®) ^

time of the appearance of the somites t e neural plate has thmkened , considerably and the neural groove ' has deepene (Figs 120 and 274B); antmorly t e margin of the plate has become more sharply defined from the adjacent ectoderm at the so-called neuro-ectoderm j or neuro-somatic juncppn The plate'^lS-tiow-^k'^gate ^omewL

shpper-shape^rea, which IS Imoa e

b.-lobed antmoriy;'sl.ghtly nWf " Its intermediate portion/ but shghtl? expanded befcaudally on either side of P

With the increase in embryonic discr and

growth changes at Hensen’s node and^^^^

primitive streak (page 49 )’

Fig 274 --SchemaUcsect.ons^throu|h^^^^^^^^^ groove, neural tube and embryos. The

successively older (A-F) gnd dermatome

differentiation of the myotome ana u




plate also extends backwards so that the blastoponc opening comes to he within its caudal extremity In subsequent somite stages the elongation of the neural plate keeps pace with the increase in length of the growing disc and, at the same time the anterior bi lobed part extends forward as bilateral elevations which become further accentuated b> the formation of the head fold (Fig 84)

B> the 7 somite stage (Fig 275) the two lateral margins of the neural groove meet dorsally m the middle line m the region of jhe fourth t«3_theji> th»8Qimtes>nd fuse to form the neural lube (Figs 122, 123 and 274C)

At this stage the cephalic two thirds of the neural plate and tube i c as far caudal as the fourth somite constitute the pnmordium of the future brain ^Whe portion of the plate and tube behind this level represents the upper cervical region of the future spinal cord The part of the neural plate from which the remainder of the cord will develop has not yet appeared B> the lo-somite stage (Fig 98) closure of the neural groove has progressed anteriorly in front of the somite region and postenorly to the level of the tenth somite The still unclosed ends of the central canal of the neural tube where It communicates freely with the amniotic cavity are called the anterior uxd posterior neuroporen (Figs 98, 99 and 276)

The 14 somu^^ge embryo shows further progress in the closure of the neural tube (Fig 99) By the 2o-somite stage (Fig too) the anterior neuropore is completely closed and this is soon fbllowed (25 somite stage) by closure of the postenor ncuroporc

In late somite stages therefore the central nervous system is represented by the walls of a hollow tube which is bent in conformity with the dorsal convexity of the embryo and is dilated cramally (Fig 163) \rost of this tube lies dorsal to the notochord but its antenor extremity projects beyond the notochord above the stomatodaeum Its caudal portion is m communication for a time with the

hindgut by means of a small opening the_nea i:enteric^ n£l, presenting the original blastopore and notochordal canal (see page 49 and Fig 48} Smceih^neural plate and, later the neural tube are conunuouslv being added to at their caudal extremity until the complete embryonic axis is laid down differentiation of the neural tissue of the caudal part of the spinal cord IS not completed until the period of somite formation ceases


Before describing the developmental changes which the neural tube as a whole undergoes to form the brain and spinal cord a bnef account will be giv en of the histogenetic change by



which the columnar ectoderm of the tube is converted into nervous tissue. These changes are essentially the same in all parts of the tube.

The neural tube is initially formed by a single layer of columnar cells, the neural or medullary epithelium (Fig. 277, I) This epithelium proliferates so that the wall of the tube becomes several layers thick (Figs. 120, 274, B and C, and 275). The nuclei, however, soon tend to group themselves nearer to the central canal so that the appearance is that shown schematically m Figs. 277, II, and 274, with an inner nucleated (germinal) layer (A) and an outer non-nucleated cytoplasmic layer (B and C). It was formerly believed (Hardesty, 1904) that the cytoplasm of the cells m the outer layer (B and G) united to form a syncytium but this IS now generally considered to be unlikely (Harrison, 1910; and Sauer, 1935) With further development the cells of the neural tube become differentiated into either neuroglial (sustentacular) or nerve cells




Certain of the medullary epithelial cells remain, for a considerable period, attached by their cytoplasmic processes to the so-called internal and external limiting membranes of the neural tube (Fig 277, II and III). These are the spongioblasts which, in later development, separate from the limiting membranes to give origin to aslrocytoblasts and astrocytes (Fig. 277, III). Other medullary epithelial cells lose their attachment to the external limiting membrane, but remain attached to the internal limiting membrane forming the ependymal cells which line the central canal of the spinal cord and ventricular system Yet other medullary cells lose their attachment to both limiting membranes very early and group themselves in a layer (A) where they become rounded and form so-called germinal cells (Fig 277, )

Unlike the spongioblasts and prirnitive ependymal cells which give rise on y to sustentacular cells of the adult nervous system, the germinal cells give origin to generations of cells which, by su seq^^^^ differentiation, may become either definitive nerve cells or further cells ot the susten ac variety. Fig 277, IV, shows schematically the stages m the differentiation of a into sustentacular cells In this process the germinal cells separate from the „2]

as undifferentiated cells (M), called medulloblasts (Bailey and Cushing, 1926; en e , which may give origin to neuroglial cells of either the astrocyte or oligodendrocyte former, which differentiate earlier, appear to be concerned with the nutrition an support of the developing nerve cells The oligodendrocytes, which are relative y ate in




Fig 276 — Anterior view of reconstruction of cranial portion of neural plate in a lo-somite human embryo (after Corner, 1929) The anterior neuropore is still widely open The pnmordia of the optic areas are outlined The area of the fusion represents the position of the future optic chiasma X c 95

1- — e, — , T. tbp nerve fibres

tiating, may be concerned with the development of the myelin sheatns o

within the central nervous system

nervous system oHial cells

Microglia. In the adult central nervous system, m addition to t ^ of ectodermal origin (ependymal cells, astrocytes and oligodendrocytes), these

sustentacular cells, collectively called microglia. Rio-Hortega (1921), w o gyidencc

cells in detail, considered them to be of mesodermal origin n There is, owever, s jjgj.yous to support their derivation from neural crest cells Microglial cells do not appear



™tcm unul It has been .ntaded hi Mood sesseb and the} maj be demat. ves of the connectne tissue cells of the sasculat adscntitia or eten be dented from the blood hisnoQ-tK It has been suggested that certain areas of the nenons system arc more actiteli intaded b> so-called fountains of micro lia than others (Penfield 1932)


In th»- tv all of the neural tube the nerve cells arise bv the dmsion of certain of the germinal cells in the epend^mial la^er (Fig 278) In the earlier stages of dev elopment when such a cell dmdes one of the daughter cells remains as a germinal cell in the cpendjTnal lajer (A) the other in apolar neuroblasl passes into ^ 3,^.

the zone immediately external to this j jj ^ — ' -**- .

layer The apolar neurohlast is \ I

similar to and may be identical with 1

a mcdulloblast (Fig 277 IV) The *1 1

apolar ncuroblast dev clops processes J

at opposite extremities to form a /* f /"o^ ' /

bipolar neuToblast (Iig 278) Subsc • I

qucntlv one of these processes retro- ^ y

grosses and a uni/io/ar nmoWaJt results

In the next stage the cell m the ^ ^

region of the retrogressed process

develops numerous small cvtoplasmic .iL _

outgrowths (primordial dendntes) m I 1 ,

this IS the stage of the multipolar | N JC, ^

neuroblasl which bv growth and I * ^

further dilTerenttation becomes a 1 • 7“ ” Vc-J 1

nerve cell Ibese stages m the r " '1% //

development of the nerve cells occur / * * / 1 ^

in the mantle or nuclear layer (B m — — J • \

Fig 278) ofthe neural tube which if

external to the ependymal or germinal /trf * i ' II

zone (A) but does not reach to the j j \ jj

surface of the tuhe The peripheral > '•h.Zy jf

area devoid of nuclei of developing

nerve cells but containing neurogbal //

ceils and processes of the nerve cells

IS called the marginal ^one (C m Fig *77 —Schematic stages m the development of gUal elements t., .k_ .L _ J t the w»l* of the neural tube ME — medullary epithelium

27 ) In the adult the ependymal jlm and EL\( — internal and external hmiung membranfs layer persists as the epithelial limng C — germinal cell E— ependymal cell S-^pongioblast

of the cavities of the central nervous

_ t J ^ Ot)B — oh«)dendrtblast ODC — obgodendrocyte MG —

system including the coverinp- of the microglia ART— artery A— ependymal zone B and C — choroid plexuses the mantle laver mantle and marginal zones becomes the grey matter and the

margmaJ layer becomes the while matter of the central nervous syxtcm In certain regions however notably the cerebrum and cerebellum the marginal zone is secondarily invaded by nerve cells from the mantle layer to form asupcrficiallayer of grey matter or cortex

The cytoplasm of a multipolar neuroblast is imtially homogeneous but at about the 5 mm stage neurofibnllae can be identified m some of them At a considerably later stage chromophJ substance (Nissl s granules) appears While these changes are occumng the dendntes become more complex and establish contact with adjacent nerve cells or their processes The axon grows actively and may extend to other parts of the wall of the neural tube (association neuron) in w hich case u passes usually by w ay of the marginal zone or it may grow through the marginal



zone, pierce the external limiting membrane and pass, as a motor fibre, to an effector organ. The axon of an association neuron may remain as a naked cytoplasmic process (non-myelinated fibre), or it may develop, possibly under the influence of the oligodendrocytes, a myelin sheath (myelinated fibre). The axon of a motor neuron always acquires a neurolemmal sheath as soon as It leaves the surface of the neural tube, but such a sheath is never found within the central nervous system The axon of a motor neuron usually also develops a myelin sheath (Fig 278, NC 2) which IS found on it both within and without the central nervous system. The myelin sheath of an axon within the central nervous system first appears near the cell body and extends to near the termination of the axon; if such a fibre passes out of the central nervous system,

as a motor fibre, the myelin sheath on this peripheral portion is regularly segmented by constrictions which are called the nodes of Ranvier. Nodes can also be identified on central fibres but they are not so obvious The occurrence of these nodes is possibly due to the fact that the peripheral myelin sheath is laid down under the influence of the neurolemmal cells, and the central myelin sheath under the influence of oligodendrocytes, each segment of myelin representing the activity of one of the non-nervous cells.


In the human central nervous system myehnation commences in fouil ^ month.



Fig 278 — Schematic stages in the development of a motor neuron AN — apolar neuroblast, BPN — bipolar neuroblast,

UPN — unipolar neuroblast, MPN — multipolar neuroblast, NC — nerve cell with naked axon, NC i — nerve cell with neurilemmal sheath on peripheral part of axon, NC 2 — nerve cell with medullated axon, other abbreviations as in Fig 277

nf foetal life (loo-mm. stage), but it is not completed until the sespntLor .third year a fter b irth It does not occur simultaneously along the who e length of a fibre but begins close to the nerve cell, and then spreads along the fibre to near its termination The sheath appears at widely varying times in different re systems In general it appears hrs in those fibre systems that function earliest or are the oldest phylogenetically. There is much evidence (Langworthy, ^^9^7 and 1929) that tracts become myelinated at about the time they become functiona , myehnation is certainly not an essential corollary of function” (Windle, i94o) Myelination in the Spinal Cord. The cervical part of the cord is the first to develop myelin and from here the process of myehnation extends in a caudal The intersegmental fibres in contact with the anterior grey columns are the first to e myelinated and, a little later, the ventral commissural fibres. The ventral root r myelinated before those of the dorsal root. The posterior columns of white matter be myehnated at the sixth month of foetal life, the spmo-cerebellar and spmo-t a ami ^ at the seventh month The descending motor tracts (pyramidal and rubro-spina j on y



to acquire their m^elm sheaths at full term and the process is not complete until the second year of post natal life

Myelinatioo vn the Brain The cranial ner\es of the rhombencephalon (pons and medulla) and mesencephalon (midbrain) first shmv signs of myelmation at about the sixth month of foetal life the motor fibres being mielinaled before the sensory The \estibular nerve is the first sensory root to be myelinated the cochlear 1 distinctly later Myelmation does not begin in the optic nerve until about full term Of the brain tracts the medial longi tudmal bundle is the first to show my chnation (sLxth month), but is soon follow ed by the \ estibulospinal reticulo spinal and tecto-spinal tracts No eflcrcnt thalamic pathways are myelinated as far as the thalamus until the eighth month The cerebellar connexions are also myelinated in the eighth month The cortico ponto cerebellar connexions become myelinated at about the same time as ^ the pyramidal tract In the cerebral cortex projection areas become myelinated before correlation areas (FIcchsig 1876) On the basis of the time of myelmation of the fibres It is possible to classify the cerebral cortex into a *

number of distinct mychnogenetic zones The study of the time and sequence of myelmation of the central nervous system has proved to be of great value in the study of the ongin coune and termination of fibre groups within the central nervous system


As has been noted earlier the peripheral nervous system is in part derived from cells of the neural tube which give ongin to the motor nerve fibres of the spinal and cranial nerves The sensory cells and fibres of the peripheral nervous system (wxth a fevv exceptions vvhich will be mentioned later; and probably many of the peripheral cells of the autonomic nervous system are denved from the neural crest The neural crest anses as a stnp of specialized ectoderm flanking the neural plate and interposed between it and the somatic ectoderrn (Fig 279^) \Nhcn the neural plate becomes depressed to form the neural folds the pnmordium of the neural crest IS found at the ncuro somatic junction (Fig 279BJ \\ ith the closure of the neural folds to form a neural tube and the associated fusion of the somatic ectoderm donal to this tube the neural crest of each side appears as a column of isolated cells along the dorsal aspect of the neural tube (Figs 274 and 279C) Subsequently the neural crest cells migrate venlro Uterally and come to he along the dorso lateral aspect of the neural tube (Fig 279D) where at the iCKsomite stage they form an mierrupted column of cell on either side of the developing nervous system reaching from the future mesencephalic region to the level of the sixth somite (Baxter and Boyd 1939 Theilcr iqj 8 and 1949) In the somite region the neural crest cells which in part give origin to the postenor root gangba be between the neural tube and the somite (Fig 274D) Further neural crest cells develop with the caudal elongation of the neural tube and this further production continues until the closure of the postenor neuropore The neur^ crest tissue from before backw ards may now be subdivided mio the following pnmonba (i) Tngeminal (2) Facial and Auditory (3) Glossopharyngeal and Vagal complex (4) Occi pital and fs) Spinal These pnmordia with the exception of the occipital which appears

o 2(9 — Traniverv lecuons of four early human embryos to show ongio of neural ernt Based on A— Heuser pre soiiute B— Payne 7 somite C — Comer lo-somite and D — Heuser 14 somite embryos



to retrogress, give origin to sensory cells of the cranial nerve ganglia and, by segmentation of the spinal pnmordium, to the chain of spinal posterior root ganglia.

While It is generally agreed that most of the cramal and all of the spinal sensory ganglion cells arise by differentiation of neural crest cells, there has been much discussion on the possible additional potentialities of these cells. There is evidence, derived especially from experiments on the development of lower vertebrates, that the neural crest cells can differentiate into the following cell types (Fig 280) —

(i) Unipolar dorsal root ganglion cells, and the equivalent cells of the sensory ganglia of the Vth, Vllth, IXth, Xth and Xlth cranial nerves, through the stage of bipolar neuroblasts The central process of the T-shaped axon of the unipolar sensory neuron grows into the dorsal portion of the neural tube to form a fibre of a posterior or sensory nerve root. The peripheral process joins the ventral root, or, in the cranial nerves, the corresponding motor root, to


constitute a mixed spinal or cranial nerve Eventually such peripheral processes from the ganglion cells grow out to innervate sensory receptor organs

(2) Some, at least, of the persistently bipolar cells of the auditory nerve (page 3^3) •

(3) Sympathetic neuroblasts (page 327) which may differentiate into either sympathe ganglion cells or chromaffin cells

(4) The neurolemmal sheath cells of all peripheral sensory and acceptance of this origin for the neurolemmal cells is due chiefly to the wor o (summarized m 1937).

(5) It has been suggested by Harvey and Burr (1926), on the basis of oiigm amphibian larvae, that the leptomemnges (pia and arachnoid) are of neura cr

This interpretation, however, has been contested by Flexner (1929) Stone

(6) Descriptive and experimental work on lower vertebrates by many workers

1929, Harrison, 1937; and Horstadius, 1950) strongly suggests that cells,

head region may give rise to mesenchymal cells of the head and to branc 1 Mesench^mrie of neural crest origin constitutes the so-called rnesectoderm.



(t'J Recent experimental work (summanzed by du Shane 1948 Rawles 1947 and 1948) demonnrates that the connective tissue pigment cells (mclanoblast, etc ), at least in the lower vertebrates arise from migrated neural crest cells Boyd (1949) has given descriptions of these cells in the human embrvo

^8) On the basis of m\ estigations on primitive vertebrates (Cyclostomes and Euselachii) Ckmel (1942) concludes that the neural crest originally arose as an evagmation of the dorsal part (alar plate) of the neural folds or tube He regards the optiu vesicle as being the anterior extremitv of this evagination and therefore homologous with the neural crest


In somite stages when the neural tu be has closed in the future bo^y region of the ej^ryo (Figs 50 and a^AC) iKe'heural cahaT^a dorso Central cleft with thick 7 ateraTw alls and

Fio a8i — Drawings (after Screeter 1919^ ot graphic reconstructions of the spinal cord in human cm br >05 V — 30 mm B— 67 mm

Fits 8 — Schemes to shot successite stages m the development of the alar and basal laminae m the spinal cord region Alar laminae black basal laminae red

a xhm floor and roof The neural crest cells arc situated on the dorso lateral aspect of the tube butanterionootfibreshavenolyetappearcd By the end of the somite period the ventral part of each lateral wall has increased m thickness owing to the multiplication of the cells m the mantle layer and the fibres of the anterior spmal roots have appeared (Fig 274 D and E) The spinal cord now has the form of a tapenng cylinder curved in the plane of the embryonic axis Owm^ to the ventral flexure of the developing head end of the embryo there is an acute bend ihccemcal flexure at the junction of the spinal cord and the rhombencephalon (hindbrain) (Fij, 288; In post somite embryos and until the beginning of the third month (30 mm stage) the cord extends the whole length of the embryo into the developing coccygeal region (Figs 251 andsSi) Inlaterstages however thecarulages and bones of the vertebral column whichhave developedin (he mesoderm surrounding the cord grow morerapidly than the cord itself, so that bv full term the original coccygeal end oflhecord lies at the level of the third lumbar vertebra



This lesult IS contributed to, apparently, by some dedifferentiation of the caudal end of the central nervous system. Successive stages in the upward retreat of the spinal cord are shown m Figs. 281 and 283 As a result of the disproportion in the rate of growth of the vertebral canal and spinal cord all the spinal nerves below the upper cervical region pass out laterally with increasing degrees of obliquity in a cramo-caudal direction and the spinal cord itself is absent from the lower part of the vertebral canal. This region is occupied by the lower spinal nerves and by the filum terminale, which marks the tract of retrogression of the spinal cord proper As far as the middle sacral region the filum terminale and the related nerves are enclosed within the subarachnoid space. Caudal to the termination of the latter, the filum terminale lower sacral nerves and the coccygeal nerve receive only a prolongation from the dura matei

Fig 283 — Four successive stages in development of the caudal end of the human spinal cord ( Streeter, 1919) They show the formation of the filum terminale and the progressive obliquity o first sacral nerve which is caused by the differential growth of the spinal cord and vertebral co , From left to right in the figure the sizes of the embryos from which the reconstructions were are: — 30 mm , 67 mm ,111 mm and 221 mm

At full term the spinal cord is approximately 15-17 cm. in length, terminating at t e e of the third lumbar vertebra, and weighs 3 to 3-5 grams vstem

As has already been stated, the spinal cord region of the developing central nervous imtially possesses a pair of thick lateral walls, thin roof and floor plates, and a narrow c ^ lumen The mantle zone in the ventral half of each lateral wall of the spinal cord soon e ^ thicker than in the corresponding dorsal half As a result, the ventral half ® *■ ® becomes the cord becomes compressed and the thickened ventral half of each latera wa marked off from the dorsal, thinner, half by a longitudinal furrow, the sulcus hmiatu { .

and 298). The thickened ventral portion of each lateral wall is now calle t e a and the dorsal portion, which later will also become thickened, is the alar lamina. limitans marks the junction of the two laminae on the lateral wall. brain stem)

The basal laminae of the neural tube develop into parts of the spinal cor essentially

which are essentially motor in function while the derivatives of the alar laminae a



sensory ind coordmati%c Cons^quentlj the sulcus limitam marks ihc boundary between the pnmanl^ rnotor and pnmanlv sensory portions of the central ners ous S)-stcm Tlic rclativ cl> carl) de\clopment of the bisal laminar » in expression of the earl> (iifTcrcntialion of the rnotor cells of the cord compared with those densed from the ilar lamimc

The sulcus limitans extends the whole length of the spinal cord and well fomard into the brain reqion It ssas considered by His (1888) to reach to the extreme interior end of the tube but Kmi^sbury («9'*2 and 1930) and others consider that it does not extend further forsMrd than the region of the mesenceplnhc (midbrain) flexure If the htter intcrpretition is correct the bisil laminae do not extend the whole length of the deteloping nenous system but terminate antenorh in that portion of it w hich liecomcs the basis peduncuh and ennse qucntly the prosencephalon (fore brain) will be developed from the alar laminae ilone

The roof ind floor plates of

the developing spinal cord at Fic 384 Sm-u nihrous' the irmal cord m the lower cervical

least in the higher vertebntes r cionofa 14 men human emhr>o x c 58

appear to be essentially non

nervous and are formed bv

ependymal and neuroglial cells which do not give rise to neuro* blasts Their narrow marginil zones hov>evcr become the path way for commissural fibres The basal and alar laminae ire formed by the prolifcntion of the germiml cells of the ependy mal zone By difTerentntion the resulting ncuroblasts become the motor cells of the anterior horns of grey matter (bisal lamina) and the receptor cells of tlie posterior horas (liar lamma) U should be noted that the cells differentia ting in the alar laminae arc the second afTcrent neurons m the sensory pathway T he first neurons in this pathwav have their cell bodies situated in the posterior root ganglia and are derived from the neural crest Increase m size of the laminae

^ or;n£:^ ^^5

,S comp^eteiY ,^^gs 28a, caudal 1?°^"° so ^

^ediausep does uot J ^e^aius tta S

. POST /< '- — ...r, in size, DU _Toptueut a^








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i- vcbte®^'" V. the spia^^ ^ V c 27

yegion ot a 3 ancHES


V. the spinal cot 12

tg 2o 7* f o q*^ inti'

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alls ID tl^e Jer part of terminahs^ and ^^^.^^Wnoliaa, »

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theft tfte basal

t 924 rV ^eing tojects

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i^mcft eveutu Y d gtoove, ftssure, rs v

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number of cord mcreases

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numberof^® Tfteseb^ ^^al ing ' the ong'Dal ^bat

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ne becomes t^^ ^^tter,

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form tbe;V d.b^S

^he poster hecom ^g^tral

of gt^J ^ \ lateral herepDa' into dorsab

columm § hs m tb oaps troD °^'^^lertofott^'^lt occarf of gt^^ ^ Z of tb^ ; fourteeotb cftaractf'®^' w. hytftef ^ tbe telauvefy"^" 2 ^. stage) ^

V (80 2' groups 2. the

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tmbno! ccIliJimihrinappcinncclotho5croundintIicclomIroolKini;hiln'c:l.ccndccril»d

in of die spin'll cord md even m the central c-m-il nie origin and file of these cells

11 not set csnhlislicd (see Hiitnplires, mu ind mt 7 for deliili) lor dcscliipmrnt ofspiml mcnint’cs s« Scn'cnit, *Oji

lie aoi — Krconitniction of the rxtrrmi firm of the rn5hi half of the eranial pan of the central nerhout i>-*tem in an iimm human emboo (after llcclnletter igip) arrow-* it in fur ann The thin rhomi ncrplialic roof i* not ihown xc lo


In describing tlic dcvelopincm of the bmn there -ire idvantigcs in giting sepiratc descctpu<ws of sts -sppeaTaoce awi vte ooT»fig\n'»\ion atid of considering the

former first The whole of us development, as will be seen is complicated b> the presence of the brain flexures In the development of all mammals but especially in that of man there IS an early cervical flexure at the junction of the rhombencephalon and the spiml cord This flexure has its concavity directed ventrally Later a second ventral mcscnccpinhc flexure occurs m the midbram region A third flexure with i dorsal concavity then develops m the



Fig 292. — Reconstruction of the external form of the right half of the cranial part of the central nervous system in a 15 mm human embryo (after Hochstetter, 1919) The roof of the IVth ventricle has been removed X c 13.

X c 9



rhombencephalon approximately bemeen the mctencephalon and the m> elenccphalon this IS the pontine flexure Much later a telcncephahc flexure appears m the forebram region and has a maiV-ed effect on the final development of the brain This last flexure is much more marked m human development than in most other rnammals


In the primordial brain region of early human somite embryos as m other vertebrates three primary subdivisions of approximately the same cranio caudal extent can be recognized The most cranial of these mcliidis the broad bi lobed region of the neural plate which extends in front of the level of the

notochord and becomes the prosencephalon (Fi^s 275 and i6a) Close to the lateral margin of this region on each side a shallow depression the optic sulcus which in subsequent development becomes the optic evagma tion or vesicle can be seen Behind this presumptive pro encephalie region is a narrower area which ex tends to the level of the first somite and is related laterally to the thickened ectodermal area called the otic placode this narrower region forms the mesen cephdon and the cephalic part of the rhomben cephalon The remaining portion of the primordial brain region is related laterally to the first four somites of each side and it will become the caudal part of the rhomben cepVialon By the 10 somite stage closure of the neural

Fig 294 — Recoourueuon of ihc cxiernal form of ibe right half of ihc cranial pan of ihe cenirai nervous syst m in a 53 mm human embryo tafier {lochsirtter igiq) The roof qf the IV th ventricle has been retROved X c 4 5

groove has extended rramally as far as the level of the otic placodes so that the rhomben cephalic region of the neural plate has become converted into a tube The optic sulcus is now much deeper (Fig 276) and the neural plate, in the still exposed anterior portion is thickened 2nd can be recognized as the primordial thalamic region In older embrvos (Fig 99) closure has extended well in front of the otic placode and by the twenty somite stage the untenor neuropore is closed (Fig 101) and the original opuc sulcus of each side has become a lateral diverticulum the opM lesule of the prosencephalic cavity The remon of final closure of the anterior neuropore is probably represented in later stages as the lamina terminalis (Figs 163 and 273} As soon as the anterior neuropore ts closed the cavity of the neural tube m the brain ref ion shows three dilatations one in the forebram the prosencephalic cavity, one in the midbrain the mesencephalic cavnty and one m the hindbrain the rhombcncephahc cavity



The constricted region joining the mesencephalon to the rhombencephalon is called the isthmus.

The external form of the human brain shortly after the closure of the antenor neuropore is shown in Fig. 288. In the mesencephalic region there is a marked mesencephalic (midbrain) flexure and, at the junction of the spinal cord with the rhombencephalon, a less well marked cervical flexure On the ventro-lateral surface of the rhombencephalon a series of segmental elevations, the neuromeres, can be distinguished The optic vesicle appears as a diverticulum of the

prosencephalon By the 5 mm. stage (Fig Fig 295 —Reconstruction of the external form of the 380) both the mesencephalic and cervical

right cerebral hemisphere in a human embryo at ^ ^ j 1 +1,0

the 4th month of foetal life (after Kollmann, 1907). flexures have become accentuated and

X c 3 7 optic vesicle has become converted into an

optic cup (see later, page 316) With furthei development a third, pontine, flexure, which is compensatory to the mesencephalic and

cervical flexures, becomes apparent in the rhombencephalon (Fig 290), and at the same tune the roof plate of the rhombencephalon becomes thinned and stretched in a lateral direction At about the same time another diverticulum, the cerebral, or ielencephalic, vesicle, appears on each side of the prosencephalon below and antenor to the optic cup, the proximal part of which has become narrowed and elongated to form the optic stalk. By the ii ram stage (Fig. 291) the pontine flexure has become well marked and the rhombencephalon can now be subdivided into a caudal part, the myelencephalon, which is continuous caudal y with the spinal cord, and a cranial part, the metencephalon, which is joined anteriorly to the mesencephalon by way of the isthmus. The mesencephalon appears as a slightly dilate

portion above the mesencephalic flexure; its cranial limit IS marked on the dorsal surface by a small evagination, the pineal primordium, which develops from the posterior part of the roof of the prosencephalon The forebrain now consists of two laterally placed cerebral vesicles and a central portion, corresponding to the original prosencephahc vesicle, most of which becomes the diencephalon The optic stalk can now be called the optic nerve and is attached to the side of the anterior part of the diencephalon Behind and between the attachment of the optic nerves a small median diverticulum of the diencephalic floor makes its appearance, this IS the primordium of the neural, or posterior, lobe of the hypophysis cerebri

At the 15 mm stage (Fig. 292) the myelencephalon can be recognized as the medulla oblongata to which are attached the caudal cranial nerves (glossopharyngeal, vagus, accessory and hypoglossal). The pontine flexure has become still more marked, but the eminence of the pons itself is not yet established. The dorsal portion of the metencephalon IS now thickened laterally, on each side,



to form the primordium of the cerebellum but the remainder of the rhombencephahc roof 15 extremel) thin The abduccns faaal and acoustic nerves are attached at the junction of the metencephalon and the myelencephalon The trigeminal nerve is joined to the most projecting part of the ventral surface of the metencephalon The mesencephalon has become further dilated and projects slightly over the cerebellar rudiment The cerebral vesicles have enlarged considerably and can now be rect^mzed as the cerebral hemispheres The hemispheres extend backwards on the lateral aspect of the diencephalon They also project anteriorly and superiorly beyond the level of the dicncephalon so that their medial surfaces come to face each other but remain separated by mesenchymal tissue which will later form the falx cerebri A small olfactory bulb is apparent at the antero inferior extremity of each

Fic 297 — V entrsi aspeci of a rcconsinicuon of the brain of a 68 mm human embryo (after Hochsteuer 1919) X c 4 7

hemisphere The postenor lobe of the hypophysis attached to the ventral or hypothalamic portion of the diencephalic floor is now embraced by the anterior lobe which is derived from Rathke s pouch an upgrowth from the stomatodaeal ectoderm (page 892) With further develop ment the cerebral hemispheres enlarge and grow progressively backwards over part of the lateral wall of the dicncephalon {Fig 293) and later over the dorso lateral aspect of the mesencephalon (Fig 294) Eventually their caudal extremities come into contact with the dorsal surface of the developing cerebellum from which they remain separated by a condensation of connectiv e tissue w hich forms the tenimum cerebelh

The expansion of the cerebral hemispheres is not uniform so that they change their shape « th^ enlarge As their expansion is chiefly upward backward and forward the infero lateral portion of each hemisphere becomes relabvely depressed and can be recogmzcd in



subsequent stages as the insular region. The area immediately behind the insula expands and grows actively m an antero-inferior direction, below and lateral to the insula, to form the temporal lobe which later comes to he lateral to, and below the level of, the diencephahc floor region which may now be called the hypothalamus. The area above and behind the insula can be recognized as the parietal lobe and that above and m front of the insula as t\it frontal lobe. The occipital lobe is formed by the continued backward expansion of the hemisphere after the formation of the temporal lobe (cf. Figs. 293, 294 and 2295),

During the time that these mam subdivisions of the hemispheres are being established other important changes are occurring —

(A) The primordial olfactory bulbs have grown actively (cf. Figs 292-295) and come to extend forward on the ventral aspect of the frontal lobe. The distal portion of each bulb becomes dilated and thickened to form the defimtive olfactory bulb, while the proximal portion remains thinner and can be traced back, as the olfactory tract, to the medial and lateral aspects



' / / ! - ;












Fig 298 — Medial surface of a reconstruction of the right half of the cranial part of the central nervous system in an 1 1 mm human embryo (after Hines, *922) The arrows indicate the mesencephalic and cervical flexures A = limit of the lamina terminalis X c 14


of the temporal lobe (Fig 295). That part which passes laterally crosses, in its course, lower part of the insula

(B) The mesencephalon becomes relatively much smaller and its roof, the tectum,

between the postero-medial surfaces of the cerebral hemispheres and the upper sur ace ° ,

developing cerebellum (Fig. 296). The developing pineal gland lies immediately cranio

to it.

(C) With increasing development of the pontine flexure, the dorsal metencephalon becomes approximated to that of the myelencephalon (Figs. 301 an

The cavity within the rhombencephalon can now be recognized as the IVth J’jateral

extremely thin roof of this cavity becomes increasingly rhomboidal m shape wit ^ angles overlapping the lateral walls of the cranial part of the medulla (Figs. 392),

The developing cerebellum, which initially projects solely into the ventncle

soon becomes apparent on the surface at the cramal attachment of the roof oi the j^^arkcd

and just behind the mesencephalon (Fig. 251). By the 50 mm. stage it forms ^ ^

extraventricular swelling on the surface of the dorsal aspect of the brain stem (




As already described ihe casity of the cranial end of the neural tube after closure of the anterior neuroporc, shoivs three dilations corrcspondinj, to the three primary subdivisions of the brain By the 5 mm stage (Fig 163) the caudal one of these three cavities has a very thin roof and can be recogmzed in all subsequent Stages as the IVth ventricle Its ventro lateral walls constitute the rhombencephalon and on each side their ventricular aspects show up to seven segmentally arranged elevations (Fig 298) correspondingtoeqmvalentones on the external surface of the wall (Figs 288 and 289) These elevations are the ncuromeres and they are separated by mterncuromcnc clefts They disappear in later development and it has not yet been determined whether they represent a fundamental segmentation of the rhombencephalon or arc merely an expression of developmental mechamcal stresses in this region (see Adelmann

Fio gg — Ntedial surface ofa reconsinjciion of the right half of the cranial part of the central nervous s>stem m a 14 mm human embryo (after Hines igaa) The arrows indicate the principal brain flexures X c 13 5

•925) The intermediate of the three dilatations of the neural tube is situated in the mesen cephalon and hes above the mesencephalic flexure (Figs 298-300 and 302) The cranial dilatation which possesses on each side an optic evagination soon shows a division (10 mm stage Fig 298) into a postero-supenor median porUon called the diencephalon, to which the optic stalks are attached and an antero infcnor pair of laterally directed cvaginations situated m the developing cerebral vesicles and representing the future lateral ventricles The telen cephalon is formed by the two cerebral vesicles together with the most antenor portion [teUncepkalon medium) of the original proscncephalic cavity The cavity of the dienccphalon together wnth that of the telencephalon medium, can now be called the Illrd ventricle Postcrocommunicates freely with the mesencephalic cavity antero laterally, immediately Mhind the lamina tcrmmalis it opens on each side into the corresponding lateral ventricle by a large aperture the future tnlerienlnettlar foramen

Each sulcus Imiitans passes from the spinal cord through the rhombencephalon dorsal to

(Ftgs =98-300) IVhether it eatends ■utn the diencephalon is still undecided (page 373) but a groove called the hypothalamic



sulcus, on each lateral wall of the Illrd ventricle, may be the forward continuation of the corresponding sulcus hmitans to the region of attachment of the optic stalk (Fig. 298). By the 14 mm. stage (Fig 299), owing to the thickening of the rhombencephahc basal laminae, the neuromeres have disappeared With the development of the pontine flexure, and the compensatory lateral extension of the lateral part of the IVth ventricular cavity, the latter becomes rhomboidal in shape (Fig. 301) Projecting into this cavity, on each side, from the anterolateral margin of the metencephahc roof, is the primordium of the cerebellum, which at first is mainly intraventricular (Figs 292 and 302) As development proceeds each interventricular foramen becomes relatively smaller (cf. Figs 299 and 300), and through it can be seen bulging, into the floor of the lateral ventricle, the-primordium of the corpus striatum The lateral wall of the Illrd ventricle shows two shallow sulci {hypothalamic and epithalamic) which separate the primordium of the thalamus from the hypothalamus and epithalamus respectively (Figs. 299 and 310) In the lower part of the hypothalamus, at this stage, the lumen of the optic stalk







mesencephalic FLOOR (TEGMENTUM)










r: ■





^.MEDULLA oblongata


Fig 300 — Medial surface of a reconstruction of the right half of the cranial part of the central nervous system in a 43 mm human embryo (after Hines, 1922; X c 6

is Still visible and below it a thickemng in the lamina terminalis indicates the position

developing optic chiasma v, d ff entiation

During subsequent stages of development further progress is made in t e 1 Illrd of the brain cavities so that by the 40 mm stage (Fig 300) the configuration o ventricle has become more like that of the adult The interventricular forarnen is smaller and the thalamus occupies the greater part of the i^-te^al wall of the diencep separated, dorsally, from the reduced epithalamus by the epithalamic sulcus, anterior

from the hypothalamus, which is still quite extensive, by the hypothalamic sulcus ^ medial commissure can now be identified in the thickened lamina terminalis and the exp surface of the cerebral hemisphere is much larger. , rnesencephalic

The mesencephalic cavity, at the 40 mm stage, is still widely dilated, ut le trans floor has become thickened to form the tegmentum of the midbrain. Longiti^^i^^^ hindbrain verse fibre tracts have developed in the marginal zone of the basal laminae o an

to produce the pons and medulla. The cerebellum has increased in size, no


extra as well as an imia ventricular portion and the lateral recess of the IVth ventncle extends outwards and \entrall> on to the lateral surface of the medulla (Fig 297)



The rhombencephalon which becomes subdivided into m^elencephalon and meten cephalon gives origin to the medulla the pons and the cerebellum Soon after the closure of the anterior and posterior neuropores the roof plate of the rhombencephalon becomes attenuated and at the same time increased m extent Thus the alar laminae in this region become separated and each of them comes to he dorso lateral to the corresponding basal lamina (Fig 303A and B) This process results m the rhombencephalic roof plate becoming rhomboidal and \er> extensive but corresponding!) thin The cephalic portion of the rhombus forms the roof of the metenccphalic part of the IVth ventricle whereas the caudal portion roofs the m>clcncephahc part Each sulcus limitans lies m the floor of the expanded IVth ventricle (Figs 301 and 303) so that, in this region the primary motor centres in the basal laminae become situated medial to the sensory receptor nuclei of the alar laminae

MEDULLA AND PONS The medulla is derived from the m>eIcnccphalon The pons arises from the ventral portion of the metenccphalon but as will be explained it receives a cellular contribution from the alar part of the myelencephalon The develop ment of the alar and basal laminae ts somewhat different m the m>elencephaIon and metenccphalon In the former the lateral part of each alar lamina proliferates and the resulting cells migrate downward and fonxard (Figs 303B and 304) as the bulbo pontine extension and come to he m the thickened marginal zone ventro lateral to the derivatives of the basal lamina The more caudal of these cells form the ohiarj nucUar complex the more cranial contribute to the developing pontine nuclei of the basilar (ventral) portion of the pons The tegmental (dorsal) part of the pons is derived from the basal laminae of the original metcnvephalon

After the separation of the bulbo pontine extension from the m)clencephalic part of the alar lamina the remaining cells of the latter m the floor of the IVth ventricle differentiate into three groups of receptor nuclei 303®) * The most lateral of these groups is the somatic afferent group associated with the fibres of the Vlllth nerve and with the descending bulbo spinal fibres of the Vth nerve The most caudal ot the cells of this lateral group approach those of the opposite side at the spinal extremity of the IVth ventricle and later differentiate into the gracile and cuneale nuclei The intermediate {special usceral or branchial afferent) group of cells of the alar lamina of the mjelencephalon receives afferent fibres from the branchial region by way of the I\th and Nth nerves In later stages these cells migrate vcntrally and form the nucleus of the tractus sohianus The most medial {general ttsceral afferent) group of myelencephalic alar laminar nuclei lies just lateral to the sulcus limitans It contributes mainly to the dorsal sensory nucleus of the vagus nerve

of Che .ubdmsioiM (componenti) of the spinal and cranial nerves the reader reierrcd to textbooks of neurological anatomy

Fig 301 —The dorsal aspect of the floor of the I\ th ventricle of a 10 mm human embryo (after von MolIendorfT 1928)



The cells of the basal lamina of the myelencephalon also differentiate into three groups The most medial of these groups {somatic efferent column) gives origin to the fibres of the hypoglossal nerve which supply the derivatives of the occipital somites and leave the medulla medial to the olivary nuclear complex. The intermediate {special visceral efferent, or branchio-motor, column) group of cells contributes fibres to the muscles of the four posterior branchial arches by way of the IXth, Xth and-the bulbar portions of the Xlth cranial nerves. Its caudal portion possibly differentiates into the nucleus of the spinal accessory nerve. In later development this branchiomotor column migrates ventrally from the ventricular floor to form the nucleus ambiguus The

most lateral {general visceral efferent) group of cells, which lies just medial to the sulcus hmitans, gives origin to the general visceral or splanchmotor fibres of the




















vagus and glossopharyngeal nerves A portion of this nucleus, in later stages of development, becomes fused with the corresponding portion of the general visceral afferent group to form the dorsal nucleus of the vagus All the motor fibres from the cells of the special and general visceral efferent nuclei leave the medulla dorso-lateral to the olivary nucleus and in relation to the incoming sensory fibres.

In the metencephalon

the roof plate is initially thin but, as it is triangular in shape, with the apex of the triangle situated cranially, the alar laminae of this part of the developing brain approach each other as they are traced forward. The dorsal portions of the alar laminae become thickened m subsequent development to o^

the rudiment of the cerebellum (see later) The ventro-medial part of each contributes some cells (Fig. 303) to the developing pontine nuclei and t e q’jje

differentiate in situ into lateral somatic sensory and medial viscero-sensory n^^ (-ochlear caudal part of the lateral somatic sensory portion contributes to the vesU nerve. The

nuclei while the cranial part becomes the pontine sensory nucleus o t mainly

viscero-sensory nuclear group, which lies adj’acent to the sulcus hmitans, 1 ^ , contains

into the special visceral afferent component of the Vllth cranial nerve, u p some general visceral receptor cells. , . the pons,

The basal lamina in the metencephalon which forms the tegmen a p




Fig 302 — Medial surface of a reconstruction of the right half of the mesencephalon and rhombencephalon of a 23 mm human embryo (after Ingvar, 1919)



gi\cs origin to three groups of motor cells corresponding to those in the rnyclen cephalon The medial of these groups (somatic efferent) becomes the nucleus of the Vlth nerse the intermediate group differentiates caudallj into the special \nsceral efferent (branchio motor) nucleus of the Vllth nersc and cnnnlly into the corresponding nucleus of the Vth nerve The most lateral group of these ceils is represented m hter stages by the general sasccral efferent component supinor saUtar^ nucleus of the Vllth nerve The basal pontine nuclei are formeti by cells which have migrated from the alar laminae of the myelcnrephaion principally but also from those of the metencephalon In later stages their axons grow transversely in the marginal zone to enter the tlevelop mg cerebellum of the opposite side They thus give origin to the transverse fibres of the pons and to the middU ctubtUar ptJuncU (brachium pontis)

CEREBELLUM The cerebellum is derived from the dorsal part of the alar lamina of the metencephalon (fig 301) Tins part of the alar lamina of each side form* the so called rhmbte lip By the 13 mm stage (fig 30jA) the cranial part of each rhombic hp has become thickened to form the pnmordium of the cerebellum Each hp projects partly into the IVth ventricle (intraventricular portion) and partlv on the surface of ilie metencephalon above the attachment of the thinned roof plate (extraventricular portion Fig 292) The projection into the ventricle soon becomes verv marked (Figs 293 300 and 302), and by progressive extension medially m the attached margin of the roof phte, the rudiments of the two sides fuse in the middle line caudal to the roof of the mesencephalon forming a dumb bcH shaped single cerebellum Shortly after this fusion the extraventricular portion of the cerebellum becomes larger at the expense of the intraventricular part This so called eversion of the cerebellum (Fig 305B and C) is probably due to growth changes in the neighbourhood By the 80 mm stage the mam mass of the cerebellum is extraventricular m position The lateral parts of the cerebellar rudiment increase rapidly m size to form the hteral lobes and at about the 100 mm stage (Fig 305D) fissures develop on its surface The tirst of these to appear is the postero lateral fissure which separates off the nodule and the flocculus from the lemis and hemispheres respectively (Fig 306) It demarcates the most prmutivc portion phylogenetically oftheccrebellum which has its principal connexions with the vestibular nuclei (Larsell 1937 and 194.7 and Dow from

the remainder Later secondary fissures appear, at first

FiO say — A scheme to show migralion (stippled) of alar lamina cells of the thomb'c lip region to form the oJite and the bulbo pontine extens ons (Based on a reconstruetion of a 23 mm human embryo by Essick }

{ ir 3( } — \ sc> erne to ihosv ihe Jev elopmrntal history of the alar and basal laminae m the myrleneephalon (medulla) and meienrephalon (pant) The right halves of U and C are ai a liter stage of development than ihe left halves




chiefly in the vermis but later extending in a complicated pattern into the hemispheres and these give rise to the/oha of the adult cerebellum.


The cerebellar primordia at first possess the characteristic three layers (ependymal, mantle and marginal) of the primitive neural tube. Soon, however, a thin superficial cortex is formed by the migration of cells from the mantle layer at the region of its junction with the roof plate (rhombic lip). These cells spread below the external limiting membrane on the superficial aspect of the marginal layer (Fig. 307A). In later stages (Figs. 305, D and E, and 307, B and G) cells of the mantle zone multiply to form the dentate and related deep cerebellar nuclei and, at the same time, some mantle zone cells migrate towards the surface into the marginal zone to form the Purkinje cells. The definitive cerebellar cortex IS formed by the Purkinje cells together with cells which migrate deeply from the superficial cortex and differentiate to form the granular and Golgi cells Thus the definitive cerebellar cortex arises partly from the mantle layer and partly from the superficial cortex. The latter normally disappears m later development so that the molecular layer of the adult cortex consists only of dendrites and axons of the nerve cells (Fig. 307G). The axons of the Purkinje cells pass to the dentate nuclei and the fibres from the latter grow forward into the mesencephalon constituting the major part 0 the superior cerebellar peduncles. The afferent connexions of the cerebellum come from a number of sources. The earliest of them is derived from the vestibular nuclei and from t e vestibular nerve itself (Larsell, 1935 j 1938) and IS soon joined by fibres from t e pontine nucleus of the Vth nerve and later y anterior and posterior spino-cerebellar trac s. Finally the development of the ponto-cerebeliar fibres and of the cortico-pontine tracts bring the cerebellum into functional connexion wicn

the cerebral cortex. A study of the p y genetic history of the cerebellum and tee


jresent the position of the median p


of ils de\c\opmcnl demonslrate that u arises as a specializajion of ihc \cstibular s>-stem of nuclei (Dow, 194a Stefnnclli 1930 and Larseli 19177


Soon after the closure of the neural tube m the rhombcncephalic region the roof plate here becomes stretched and thinned (Figs 163 303 and 335) These clnngcs arc accentuated b> the formation of the pontine flexure (Fig 338) The roof plate which is rhomboidal in shape, consists at first onb of epcndvmal cells llarntna choroidea tptthelialis) but it is later reinforced exiemalh b\ pia mater to form the tda thotoxAta of the I\ th ventricle At about the 20 mm stage (Fig 302) folds of the tela project into the \cntncuhr ca\nl> to form the rudiment of the choroid pl/cxis ^\lth further accentuation of the pontine flexure the lateral recesses of the \cntnclc are produced Blood vessels extend into the folds of the tela from ihe pia through the choroidal pssure of the I\ ih vcntnclc which marks the line of invagination (Figs 303 and 306} The area of the tela between this fissure and the cerebellum is slightlv thickened and becomes the inferior medullary relum Shortiv after the 100 mm stage the tela

in the middle line shghti) behind the region of the choroidal fissure becomes cxtremel) thin and bulges as an ependymal diverticulum (Fig 308; into the ovcrljang arachnoidal reticulum Later apparently (Wilson 19377 die ependyma of this diverticulum disappears and a free communication the median aperture is established between the I\ th vcntnclc and the subarachnoid space A lateral aperture in the roof of each lateral recess is probably produced in a similar manner These apertures permit the ccrebro spiml fluid (C S F ) produced within the ventncles by the choroid plexuses to escape into the subarachnoid space The CSF gradually permeates the cndomeninx (page 342) partially separaung it into outer arachnoidal and inner pial layers The persisting connexions between the two layers form the arachnoidal reticulum The imersliccs of ihe rcuculum constitute the subarachnoid space Eventually the subarachnoid space extends round the whole central nervous system In parts it becomes more extensive to form the cistemac


The midbram is developed from the walk of the mesencephalic vesicle The cavaty of this vesicle becomes relatively very much reduced m size dunng development to form the



aqueduct. The part of the walls dorsal to the aqueduct becomes the tectum. It consists of the two alar laminae together with the original roof plate. The portion of the midbrain ventral to the aqueduct is often called the cerebral peduncles. Developmentally these peduncles consist of a dorsal part, the tegmentum, and a ventral part the basis pedunculi. The tegmentum represents the basal laminae together with the floor plate. It develops into the nuclei of the Illrd and IVth cranial nerves and possibly into the red nuclei and the substantia nigra (these nuclei are considered by some to have migrated from the alar laminae, see Fig. 309B) The tegmentum also comes to contain the ascending sensory tracts (medial lemniscus and spinothalamic tracts), descending extra-pyramidal pathways and certain cerebellar connexions, The bases pedunculi, sometimes called the crura cerebri, consist of superficial fibres, superimposed on the ventral surface of the tegmentum where they pass in the marginal zone. These fibres arise m the cerebral cortex and pass to lower centres as the cortico-spinal (pyramidal), corticobulbar and cortico-pontine projection systems.

Fig 307 — Schemes to show successive stages in the differentiation of the cerebellar cortex The superficial cortex and its derivatives are shown in red The arrows m B indicate the probable migration of the cells

The general development and relations of the mesencephalon have been descri e ,

The development of its external form is seen in Figs. 289-294, 335 and 336, an ^ ^

form in Figs. 298-300. By the 23 mm. stage (Fig. 302) it appears as a dilated thickened roof and floor plate overlying the apex of the mesencephalic flexure. e p^^^

extremity of its roof plate overlaps the cerebellar rudiment, to which it is joine ^ of the isthmus which becomes the superior medullary velum. Gaudally ..j-jction

by way gf the isthmus with the IVth ventricle and cramally through another s ig c

with the Illrd ventricle. _ , -pnarated by

For a time the tectum appears as a pair of bilateral longitudinal ^ deprcs a median depression representing the original roof plate (Fig. 296). Later a gn

sion appears nearer the posterior margin of each longitudinal elevation ivi remains

anterior {superior) and Zl posterior {inferior) colliculus (Fig. mesermep a ic

as a distinct dilatatiop for a long period, but the thickenings produced ^ ^ cavity to

of the colliculi and the development of tracts in the mesencephalic floor re u a narrow canal, the aqueduct.



DIFFERENTIATION OF THE MESENCEPHALON At an early stage (Fig 309 A) the floor and roof plates of the mesencephalon become much reduced by the medial extension of the basal and alar laminae The boundary betsveen these laminae is indicated by the sulcus limitans In subsequent development (Fig 309B) the cells of the mantle Ia>er of each basal lamina proliferate and the resulting neurons become separated into a larger medial (somatic) and a smaller lateral (visceral) group At the lev el of the superior colliculi the medial group forms the somatic eflerent nucleus of the Illrd nerve Opposite the inferior colliculi this group gives ongin to the IVth nerve nucleus The small lateral group IS only found on a level with the superior colliculus where it becomes the general visceral efferent (Edinger Westphal) nucleus of the Illrd nerve

The cells of the mantle zone of the mesencephalic alar laminae partly by migration into the marginal zone (Fig 302B) become arranged into the stratified layers typical of the adult colliculi Some cells of the alar lamina however appear to migrate ventrally where they proliferate in the marginal zone of the basal lamina ventro lateral to the nerve cell groups of the latter and give origin to the n!/c/«tr and jt/Aj/an/w mgm Shaner (1932) however con siders that the red nucleus differentiates in stlu m the basal lamina That part of the mesencephalon ventral to the substantia nigra becomes the pathway for descending tracts from higher centres

All the fibres from the Illrd nerve nucleus grow ventrally through the medial part of the red nucleus and the medial extremity of the substantia mgra to emei^e on the medial surface of the peduncle In this instance therefore cranial general visceral cfTerent fibres leave the nervous system ventrally m association with the somatic eflerent fibres The fibres of the IVth nerve grow dorsally around the cerebral aqueduct and after decussating emerge on the dorsal surface through the superior medullary velum This atypical course of a nerve which apparently is to be regarded as somatic efferent in nature has never been adequately explained


The prosencephalon which becomes divided into the diencephalon and the telencephalon gives origin to all of the central nervous system cranial to the midbrain As has been explained earlier many embryologists consider that the prosencephalon is formed of alar laminae alone In late somite embryos (Fig 288) the prosencephalon appears as the slightly dilated cramal end of the neural tube It is directly continuous caudally with the mesencephalon and possesses on cither side a lateral diverticulum the optic vesicle By the 9 mm stage (Fig 290) each optic vesicle has become modified to form an optic cup which is joined to the lateral wall of the prosencephalon by the hollow optic stalk The portion of the prosencephalon below a^nd m front of the attachment of the optic stalk now shows on each side a slight lateral dilatation the pnmordium of the cerebral vesicle The two cerebral vesicles and the cranial unpaired part (telencephalon medium) of the original prosencephalic vesicle with which they com municate constitute the telencephalon The remaining caudal unpaired median portion of e original prosencephalon is now called the dicncephalon

By the 11 mm stage (Fig 291) the subdivision of the prosencephalon into diencephalic and telencephalic parts is v\ell marked The lateral vcntncles at this stage (Fig 298) are still ””

129 mm human embryo (after Wilson 1937)



of the Illrd ventricular cavity near the interventricular foramen. The paraphysis is found in human embryos (Bailey, 1916; Krabbe, 1936) and can persist to give origin in post-natal life to cysts of clinical importance (Bull and Sutton, 1949).

Fig. 31 1 — Sagittal sections of the developing hypophysis cerebri (pituitary) m four human embryos to show successive stages m its differentiation The anterior part of each section is to the right (Modified from Atwell, igi8 )


Hypophysis Cerebri. Before the closure of the anterior neuropore a small ectodermal diverticulum, Rathke’s pouch, appears m the roof of the stomatodaeum and extends, immediately in front of the buccopharyngeal membrane and the tip of the notochord, towards the floor of the diencephalic portion of the neural plate (Figs, 375 and 162). When the buccopharyngeal membrane ruptures, the dorsal site of the junction between ectoderm and endoderm in the roof of the primitive buccal cavity is indicated by the opening of Rathke’s pouch (Fig. 163). It was formerly considered that endoderm contributed to the pouch but it is now generally accepted that the latter is purely ectodermal. By the 14 mm. stage (Fig. 31 1 A) the pouch, which has become constricted at its attachment to the pharyngeal roof, is m contact superiorly with a downgrowth, the infundibulum, from the floor of the diencephalon. The infundibulum gives origin to the stall and the pars nervosa of the defimtive hypophysis. Rathkes pouch loses Its attachment to the pharyngeal roof by ruptuie of its original stalk and develops into the anterior lobe of the definitive hypophysis (Figs 31 1 and 312). After contact is established between Rathke’s pouch and the infundibulum the former undergoes great modification The cells of its

anterior wall actively proliferate and gradually encroach on the lumen of the pouch until finally it is reduced to a narrow cleft. This proliferation establishes the pars anterior of t 0 hypophysis and from its upper part cells extend along, an eventually around, the pituitary stalk, thereby forming t ie pars tuberalis. That portion of Rathke’s pouch in contact wit the pars nervosa and separated by the remnant of the origina lumen (residual lumen) from the pars anterior remains t iin as the pars intermedia (Fig. 31 1). The pars intermedia, m ic human, never develops extensively, it remains vascularized and its basophilic cells are devoid 0 granules. Some workers state that some of its ce s migr

Fig. 312, — Lateral (A) and caudal (B) aspects of the developing hypophysis a 5 months human foetus (after Tilney, 1936)


into the pars ner\osa In those vertebrates m which there is no close contact between Rathke s pouch and the mfundvbulutn a pars intermedia cannot be distinguished

During Its development the pars anterior of the gland becomes richly vascularized and Its cells become arranged in intermingling columns to form a meshwork surrounding the blood vessels At the beginning of the third month some of these cells accumulate acidophilic granules (Cooper 1925) while basophilic granules begin to appear in others a little later {3^ to 4 months) most of the cells however remain chroraophobic The cells of the pars intermedia and pars tuberalis arc chiefly chromophobic throughout foetal Ufe

The cells of the pars nervosa which arise from the neuroglia of the infundibular process become modified in the later stages of development to form the so called pitme^tes (Shankhn 1940) Few or no nerve cells differ entiate m the pars nervosa but many nerve fibres grow into it by way of the pituitary stalk from the hypothalamic nuclei

Pineal Gland This appears early m development (to mm stage) as a small evagination of the roof of the posterior part of the diencephalon (Fig 291) The resulting outgrowth extends upward and slightly fonvard remaining hollow for a considerable period Eventually however it becomes solid as the result of the proliferation of the cells of Its walls and us neuroglia differentiates into pineal cells Cranial to the stalk of the pineal the habenular commissure develops m the roof plate of the dicncephalon and caudal to it the posterior commissure separates the diencephalic roof from the tectum of the mesencephalon (Fig 3'’8) Nerve fibres pass from the epithalamus along the stalk to the pineal The apex of the gland IS intimately related to the great cerebral vein in the space between the caudal pole of the hemispheres and the roof plate of the mesencephalon (Fig 296) The exact significance of the pineal is still in doubt Us position suggests that it is at least in part, the homologue of the so called third or parietal eye oflowcr vertebrates (Gladstone and \Vakeley 1940 for discussion) but Us mode of development and adult structure do not support the idea that it is merelv a 'estigial organ ^

Diencephalic Gland Scharrer and Scharrer (1937) have shown that a number of he nerve cells m the diencephalon become differentiated in such a manner as to suggest that they produce a colloidal secretion which may have an endocrine function ^

in a 13 mm human embryo (after Hochsteiter igig) X c 18 5

Fig 314 — Transve cephalon in a 15 stetter 1319} >

section through the prosen m human embryo (after Hoch




The cerebral vesicles arise at about the g-mm. stage as lateral evaginations of the prosencephahc cavity (Fig 291). Each vesicle soon dilates (Figs 292-300) and its cavity, the lateral

ventricle, remains in wide communication with the Illrd ventricle through the interventricular foramen (Fig.

313) . The vesicle actively expands upward, forward and backward, but to a much lesser extent downward (Fig

314) . In the basal part its wall soon becomes much thicker than in other regions. The backward expansion of the two vesicles brings their caudal portions lateral to the upper part of the diencephalon (Figs. 292 and 293), while above and in front of the diencephalon they come into contact with one another In this manner the flattened medial surfaces of the cerebral hemisphetes are formed The connective tissue lying bc' tween the contiguous surfaces of the hemispheres becomes the falx cerebri (Figs 316 and 319). Each hemispheie can now be divided into a thicker basal or sinatal portion, which will give rise in subsequent development to t le corpus stnatum, and a thinner ivalled supra-striatal portion, the pallium, which is the primoidium of the cere ra

Medially, along 1 ® to the dience

Fig 315. — Reconstruction of the prosencephalic region in a 17 mm human embryo The anterior part of the reconstruction has been removed and the remaining portion is seen from the anterior aspect The white arrow is lying m the left interventiicular foramen (after Hochstetter, 1919) X c 19



attachment v.. phalon, each palhal wal becomes very thin (Figs. 3 ' and 3t7) ^nd projects in 0 the cavity of the ,

mg lateral ventricle as tela choroidea (Figs 3’5 qi8). The line of invagination, which first

the level of the interventricular foramen, is known as the choroidal fissure. It t tlie from the posterior ivall of the foramen along the medial wall of the cerebra erni p latter expands caudally. Above the region of attachment of the choroid P ^ on the wall is thickened and bulges into the lateral ventricular cavity (Fig. 3^51 °



316 — Transverse section through the prosencephalic region of 17 mm human embryo (after Hochstetter, 1919) X c 14



cle\ation the hippocampus Thu n indicated on the medial surface of the hemisphere by a corresponding longitudinal groove the hippocampal fissure 'vhich lies above and parallel to the choroidal fissure (Fig 310) The medul wall of the hemisphere above the hippocampus together with the dorsal and lateral walE of its supra striatal portion is the pnmordium of the so called mopallial cortex which develops in close association with the thalamus and receives from it afferent impulses of non olfactory origin from the body gencralK (Fig 326) The thickened zone lateral to the dev eloping corpus striatum is at first free from neuroblasts but cells soon migrate into this region (Fu 319) to give origin to an irregular cortical formation, the so called palaenpalhum (pynform cortex) which recaves the secondary olfactory neurons from the olfactorv bulb

Further enlargement of each hemisphere and differential growth in its wall result m changes m its shape and m its extension further backward so that it progressively covers from the lateral aspect the dienccphalon the mesencephalon and the upper portion of the meten ccphalon (Fig 320) These changes in shape result in the formation of the frontal temporal and, later by backward projection occipital lobes (Fig 294) Owing to a relative restriction in the growth in the region between the frontal and temporal lobes, i e in the region lateral to the developing corpus striatum this area becomes depressed to form the msula (Figs 294 and 295) above and behind which the parietal area soon becomes apparent With continued surface expansion at a rate greatei than the growth rate of the hemisphere as a whole the cortical areas develop convolutions and sulci (Fig 321) the latter lying either w ithin regions of special growth axial sulci or between such regions limiting sula The insular area is gradually overgrown by the adjacent cortical regions which overlap it to form the opercul » $0 that by birth it is nearly completely covered The apposition of the free margins of the insular opercula forms the anterior part of the lateral sulcus (Fi* 3^2) (For details of F*® 3 * 7 — Iransv me section through the prosencephalon

development of cerebral sulci consult *" a *9 mm human embryo (afie. Hochstettcr 1919) Connolly 1940 1950 and Friant 1947) * *'

While the surface of the cerebral hemisphere is undergoino’ the changes described, correlated modifications are occurring in us interior The lateral ventricle extends backward with the expansion of the hemisphere (Fig 318) and with the formation of the temporal lobe it is bent ventro laterally to form the inferior horn (Fig 321) W hen the occipital lobe is established a further extension of the ventncular cavity caudally into this region of the hemisphere forms the posterior ventncular horn

At the same time as the ventricular cavity is enlarging and changing its shape important growth changes occur in the basal striatal region of its floor and m the wall of the developing cortex (pallium) T hese changes brinw about further modification in the shape of the v entncle and result in the establishment of the corpus stnatum and cortex

Corpus Striatum The striata! region first appears as a projection of the base of the telencephalon into the ventricuUr cavity at the level of the interventricular foramen (Figs 3 * 3 - 3 * 5 ) It IS formed as the result of marked proliferation of the germinal zone m this region and it can soon be subdivided (Figs 316 and 318) into a medial and a lateral striatal elevation vith the expansion backward of the cerebral hemisphere and its contained lateral ventricle he striatal elevations form longitudinal ndges m the floor of the mam part of the ventncular



cavity (Fig. 323) ; when traced caudally, however, they he in the anterior wall of the descending portion of the ventricle and in the roof of the inferior horn (Fig. 321). This relationship is due to the fact that the striatal elevations bulge into the lateral ventricular cavity as it expands caudally and laterally. The line of invagination of the choroid plexus lies dorso-medial to the medial striatal elevation in the anterior part of the ventricular cavity, but as the choroidal fissure follows the medial margin of the developing corpus striatum it lies below it when traced to the inferior horn of the ventricle. Similarly the hippocampus is situated dorso-medial to the choroidal fissure m the anterior part of the ventricular cavity, but is mfero-lateral in the inferior ventricular horn (Fig. 326).








Fig 318 — Reconstruction of the prosencephalic region of a 30 mm human embryo, , from the anterior aspect On the right side the cerebral hemisphere has Men sec 10 to show the lateral ventricular cavity On the left side the hemisphere has ^ sectioned, though on a more posterior plane, and its roof has been removed to s o , dorsal part of the diencephalon The inset shows the structure of the developing c or invagination X c 3

  • of

While the general form of the corpus striatum is being established, axons corticofugal and corticopetal fibres in increasing numbers are passing from and to t e tiating cortex (Fig 326) In their course they incompletely separate the corpus s ria . a dorso-medial portion, which bulges into the ventricular cavity, and a veiitro- a er separated from the ventricle (Figs. 319 and 325) by the fibre pathways which orm capsule. The intraventricular projection of the original striatal swellings is t e which now lies in the floor of the anterior part of the ventricular cavity, m t ^ ^J^^j.Q.]atcral of Its descending portion, and in the roof of its inferior horn (Fig 326). ^jjyjded into a portion of the corpus striatum, which becomes the lentiform nucleus, can e 1



lateral portion the putamen, with darkl) stained cells resembling closely m structure the caudate nucleus and a medial lightl> stained portion the globus pallidus or pallidum Some in \ estimators consider that the pallidum IS difTerent m origin from the rest of the corpus strntum The> consider that it IS formed from a fonsard extension into the telencephalon of cells of dien cephalic origin (Spatz 1929 Schneider 1950) All of the cortical projection fibres do not pass through the internal capsule some pass lateral to the lenti form nucleus as the external capsuli and separate it from a flattened group of cells known as the claiistrum which lies deep to the insular cortex

The backward and downward expansion of the cerebral hemisphere bnngs the medial surface of its posiero inferior quadrant on to the lateral aspect of the diencephalon with which It fuses As the thalamus is situated in this part of the diencephalic wall the corpus striatum is brought into lateral Fic 319 — Coronal section of the left cerebral hemisphere m a relationship with it The caudate 73 n»m human embr>0 (afierKochnett r 1919) xcG? nucleus thus comes into direct contact

\Mth the thalamus (Fig 324) but the lentiform nucleus remains separated from it b> the fibres of the internal capsule These fibres pierce the line of fusion between hemisphere and dien cephalon and pass through the subthalamic region to enter the peduncles of the mesencephalon (F»g 3=6)

Cortex The greater part of the cerebral cortex fneopalhum and hippocampus) arises from the supra striatal portion of the telenccphalic \csicle The palaeopalhum however difTcrcntiates m the lateral part of its stnatal portion The pnmordium of the hippocampus is the first part of the human cortex to differentiate It anses in embr>os of about 12 mm (Hines 1922) b> migration of cells from the mantle zone m the dorso medial part of the wall of the hemisphere into the overlj mg marf mal zone (Fig 316) When the hemisphere expands caudally and \cntro litcrall> to form the temporal lobe the hippocampus follows the line of cerebral growth and appeirs on the medial wall of the hemisphere as a curved area of the pallial wall which lies parallel to the choroidal fissure separating it from the ncopallium (Fig 3>5) Owing to the rapid growth of the neopalhum surrounding the hippocampus the latter is forced in its further growth to bulge into the medial wall of the lateral ventricle especially m the developing inferior hom ^Ftg 326) The line of projection of the hippocampus into the ventncle is marked on the surface








by the hippocampal fissure which forms an arch parallel to the choroidal fissure. Antero-dorsally the two hippocampi soon become interconnected by commissural fibres, the hippocampal or fornix commissure. These fibres cross in the upper part of the lamina terminalis which becomes thickened to form the commissural bed (Fig. 328).

Although the hippocampus appears early m development the characteristic adult arrangement of its constituent cells is not assumed until late in embryonic life. Its cranial and superior portion, in association with the development of the corpus callosum (see later), undergoes marked retrogressive changes in later stages, but persists as the hippocampal rudiment (Fig. 327) Its caudal and inferior portions form the intraventricular hippocampus and the dentate gyrus. Earlier investigators suggested that the hippocampus receives axons of tertiary olfactory neurons from the palaeopallium (uncus and hippocampal gyrus) Recent research, however, has thrown considerable doubt on the alleged olfactory connexions of this part of the cortex. The hippocampus sends projection fibres by way of the fimbria, the fornix system and its commissure to the hypothalamus {mamillary bodies) and to the hippocampus of the opposite side Its other connexions are not yet fully established.

Fig 321 — Fissural pattern and The palaeopallium is the next region of the coitex to

development of the lateral differentiate; it first appears in human embryos of 20-25 mm.

ventricles arid corpus striatum upper Striatal region of the lateral cerebral wall as a result

in four human embryos 0 , 11 u to

(100 mm , 200 mm , 300 mm , of the migration of cells from the underlying mantle zone w

and 400 mm ) establish a thin cellular lamina which lies in the marginal zone

parallel to the surface of the hemisphere. As a consequence 0

the appearance of this lamina the marginal zone m this region may now be subdivide

into three layers . (a) an outer layer, which will become the definitive marginal zone 0

the adult cortex, {b) a middle layer, the palaeopallial (pyriform) cortex, and (r) an inner

layer, the intermediate zone, which separates the cortex from the underlying mantle zone.

This area of the cortex receives fibres (secondary olfactory) from the olfactory bulb an

in later stages is separated from the neopallial cortex by a deep (rhinal) fissuie.

After the appearance, in the striatal region,

of the pnmordium of the pyriform cortex (palaeopalhum) a cortex is progressively established m the supra-striatal portion of the cerebral wall. This supra-striatal cortex is the neopallmm. The wall of the neopallial portion of the cerebral vesicle IS at first formed by a single layer of ependymal or germinal cells. Tangential divisions of these cells result m the rapid increase of the size of the hemisphere , divisions at right angles to the surface result in the production of a mantle or nuclear layer which, as in other parts of the developing central nervous system, is initially separated from the surface by a marginal zone (Figs. 316 and 317). At about the 30 mm. stage cells from the mantle zone migrate into the overlying marginal zone to form a superficial cortical layer. This process commences m the lateral



cerebral uall and then extends rapidK into the roof and the medial uall above the hippocampal formation It docs not take place in the frontal and occipital poles until relaiivcK late but b> the 50 mm sta^c this sheet of celb extends over the enure neopallial area of the hemisphere Fii;s 310 and 32^) Tilnev ^19331 has shown that in mammals the rc:;ion of first differcntjaiion of neopallial cortex corresponds to the panetal area of the adult to it can be traced the earliest embrvomc thalamocortical fibres In the time of lu appear ance in the rapiditv of its differentiation and in tlie carlv establishment of afferent connexions 11 holds pnonlv over other neopalliil regions If this pnoiatv has stjpiificancc in tlie interpretation ol function It mav be assumed that general b*idv seme rather than si^ht or lieann" has l>een

the predominant influence in determining the establishment of the neocorlex 1 ilnev iqjj

In the period between complete establishment of the pnmarv cortex and full term the nenpalhal cortex becomes stratified into lavers ol \%hich six are usually recognized This stratification occurs partlv bv difTerenttaiion within the pnmarv

Fi Ji3 — Drswin^ of a mod 1 of i{ e inicnor I the <ef bra! hemnph<‘rc of a 4^ 5 mm human embrvo to shov* thr n ht mtncular ra III corpus iirtatum and choroidal mvac nation nxijificd aficr Hochst^tier 1910

cortex and partlj bv later waves of migration from the mantle zone Different areas of the stratified cortex soon show regional differentiation thus the motor area develops predominant!) pvramidal cells vvhile the receptive areas visual audilorv and general

sensor) cortex) are mainlv charactemed bv granular cells Details of the process of differentiation and the factors determining it are still unknown but in man the outer

Fig 324 — Dra nijs of the d rsal surfaces of the left caudate nucleus ^d the left thalamus and of th midbra n and cerebellum in two human embryos (based in part on Hochstettcr 19191

human embryology

1 1, +4^ rlpwplnned than in lower types Conel (i939) ^942) has

‘SUTven" S.pUons oF corfcal„ and cell .ypes m .he nenly

born and in the month old infant.

Cerebral Commissures. 12







pyriform CORTEX I

CORPUS 1 " [

striatum' '











pyriform STRIATUM



THALAMUS - t ncfal coftiCtil

326 -Four schemes to show the f D A 3 D arrSlevel of interventricular

differentiation Earlier stage A and B, later stage C and D, A foramen, B and C are at a more posterior plane

appearance of the cerebral ° '^“brSTan pis T'lres'o'f™'

cFLdssural plate Thm is the route by which 8br« c^ P halv'S o

to the other When such Bbres connect ® ® g-om one side of tho b

heraTe known as commissures Other fibres and decussating <"« 

other are said to decussate. In the fa'f usually grouped together as the cerebral commissu


30 « 

The first one to -ippctr (Fig 3280) is the ar/rmrctfnuntffurr which consists of fibres (Fig 319) connecting the p)Tifonn cortices ind the olficlor> bulbs Soon after its appearance in the lower part of the commissural plate another commissure nppenrs in the phte near its attachment to the diencephalic roof (Fig 328C} this second commissure, the htipoeampd or fornix commusure connects the hippocampal areas At about the 60 mm stage fibres from the ncopallial cortex are added to the dorsal aspect of the hippocampal commissure (Fig 3'’8D) These new non olfactory commissural fibres are the pnmortlium of the corpus callosum w hich is at first a small qhndncal bundle With the increase in size and diflerentntion of the ncopallial cortex howcacr the corpus callosum increases rapidls in size and extends both antenorl) and pos leriorl> in the upper part of the commissural plate which thus becomes stretched anteropostcnorl) The expanding corpus callosum also encroaches on the adjacent hippocampal region which here becomes \cr) much reduced the 200 mm stage the splenium bodj genu and rostrum of the corpus callosum are well esiabhslicd and the commissural plate beneath It has become cxtrcmcK llnnned to form the septum lucitlum Accompansing this thinning of the commissural ►-oe

plate IS the gradual development withm it of a cavitv the cavm teplt lucidi which apficars to arise as the result of mecfianical stresses im posed b> the difTcrcnt rates and directions of growth of the corpus callosum and the hippo campal commissure fHochsictter igig and Thompson 193'’) The cavity of the septum lucidum IS sometimes called the \ ih ventricle but It must lie empha sized that it neither com municatcs with the true ventricular system nor

f-io 317 —Medial aipect of the left cerebral liemuphere in a full term human foetus 10 shov\ ihe corpus callosum and ihe hippocampal derivati es (after Tilne> i!)30)

normally m man with the exterior of the bram By full term (I ig 327) the corpus callosum

extends well backward over the roof of ihc dicncephalon from which it is separated by an area bounded on each side by the medial vxall of the hemisphere this area is occupied by meninges and blond vessels which together constitute the itluin interposKum (Fig 326) The hippocampus above the corpus callosum is reduced to a thin rudiment (indusium griseum) Behind and below the corpus callosum the hippocampal fissure can be identified and flanking this the difTerenliated pari of tlic hippocampal cortex called the dentate jyruj (Fig 3 '’?) \bove the latter the hippocampal projection fibres appear as a fringe the fimbria which can be traced upwards to become tlic postenor pillar of the fornix This passes beneath the postenor part of the corpus callosum where it meets that of the other side to form the body of the fornix v\hich extends to the posterior margin of the septum lucidum The two

components of the fornix then diverge and each passes in front of the corresponding inter ventricular foramen as an anterior pvllar of the fomix through the substance of the fore brain to the mamillarv body and hypothalamus The pyriform cortex is represented at full term by the uncus and the adjacent region of the hippocampal gyaus It is separated from the ncopallial cortex of the temporal lobe by the mcisura temporalis which represents the rhinal fissure of lower mammals this fissure is the lioundary between the pyriform cortex



(palaeopallium) which is olfactory in function and the neo-cortex (neopalhum) which is non-olfactory.

While the cerebral commissures are developing, other commissures appear in the prosencephalon These are the optic chiasma, the superior or habenular commissure and the posterior

9 MM





25 MM

528 — Sagittal sections through the brains of four human embryos to show johd

ebral commissures (modified from Hochstetter, 1919 ) Blue stipple, .!^Lte37on "’The media!

Fig 3s

cerebral coinmissures i^moainca iroin nociisicuci, iy»a/ metencephalon , red stipple, isthmus, solid red, mesencephalon, black, prosen p surface of the cerebral hemisphere is stippled in black

commissure. The optic chiasma is established early in the lower part o t e ^

it consists of fibres from the medial halves of the retinae ivhich are crossing superior

of the opposite side, in which they wll pass to the lateral genicu ate ° , ,jg„(.ephalon

colliculus. The habenular (superior) commissure develops in the roo p a ^vhIch unite

(Fig. 286D) immediately anterior to the stalk of the pineal gland, it consis


mainl) the t\so cpithalamic regions The posterior commissure de\elops behind the stalk of the pineal gland at the region of junction of the roof plate of the Illrd ventricle tvith the tectum of the midbrain and consists chiefly of the fibres joining the two medial longitudinal bundles


As m other organs of the body, abnormal dctelopment of the central nervous system may be due to genetic or environmental factors Abnormal development and differentiation of the mesodermal structures related to the nervous system may also have a marked effect on the subsequent development of the latter (Fig 329) Failure of closure of the neural groove, as^ntoxia dorsalis vMth associated non development of the related mesoderm is an occasional

anomaly This failure may extend the .

whole length of the nervous system ' J"

poslenoT rachischisis or be limited to a

particular portion of it \\ hen it occurs ^ \

m the spinal cord region the condition ^ A

IS knowTi as spina bifida Spina bifida is '

most frequently found in the lumbo

sacral region and it may be complete . . ■ | . .

(Fig 331A) or incomplete (Fig 331 ®

B-E) giving several different clinical f ’H &

forms Failure of closure of the neural |) I ^ )'

groove in the brain region is usuilly A \ *

complicated by degeneration of the ^

exposed neural plate tissue (Fig 330) y V

resulting in the condition of i r^S!X^/XJ‘

>n which the brain is represented by a I r~ ^ 1 . ^ ^

mass of degenerated neural tissue f|Q jjjj — EfTcci ©f <\inn»ic factors ©n ihe differentiation exposed on the surface of the head as a of the amphibian neural lube

r«uit or .he non d«ciopm=m or .he ::.K‘ce'’"J;r.’e

SKUll \s the degeneration of the fibres m ihe mienor

exposed neural tissue occurs after the B— neural luW surrounded by meseneh>me c>lin

d5eren..a..on ct .he cromal ’’'glljr Md.“ "ry'SlrdSnsh.) ,e.u.„„e f„m e the nerves and the eye are usually failure of ihe neural groove 10 close the floor plaie in

present m ancncephahc foetuses The contact i ith the notochord is thinned out and the nerve

r .u 1 c i_ I celt bodies are arranged along the free surface

cause ot the non closure of the neural D-neural tube underlain b> muscle the lumen is

groove m spina bifida is unknown In eccentric uh the great mass of nervous tissue on the

soine cases .here may be a secondary ?"<'

r 7 luminal and the fibres juxta muscular

eopening 01 a neural tube already E — neural tube is underlain by the notochord and

formed but in most it is probably due flanked by somites these are the normal relationships .0 an abnor„ah.y .he meehan.s™ of “ Ze^Sd™ J

maucuon of the neural plate by the notochord fafier Holtfreier 1933) underlying notochord and mesoderm

Spina bifida ts frequently found m association with faulty differentiation of the notochord and vertebral bodies (e g m the Klippel Fnl syndrome)

Complete or partial blockage of the ventricular system (e g stenosis of the cerebral aque duct Russell 1949) or unbalance between the producUon and absorption of the cerebro spinal fluid give rise to congenital hydrocephalus *

Faulty development or differentiation of the cerebral cortex results m one or other of the tormsoffongrmfa/jrfioc} If the motor cortex is involved a spastic mono or di plegia is produced

sMry^cJ'lv!*’' TVv' ■' excessive production of the cerebro-spmal fluid w,th consequent exceuive page inroutfh the iVtb ventricular roof may cause abnormalities in remote parts of the body {Ch \ III)



general the pattern of distribution of the peripheral nervous system is due to an early and intimate association between the developing nerve fibre and the pnmordium of its terminal field. Harrison (1907) showed that in vertebrates generally the innervation of a limb is determined by two factors; firstly, the source of the nerve supply is detei mined by the position and extent of the limb at the time of its origin and, secondly, the intrinsic distribution of the nerves in the limb is regulated by the segregation and the growth and positional changes of the limb tissues. It has usually been accepted that the role of the nerve fibres in the second of these two processes is a passive one (Weiss, 1939), but Piatt (1942) has advanced evidence, from experimental investigations on the growth of nerves into aneurogenic limbs of Amblystoma, in favour of an active role of the growing nerve fibres in the establishment of the normal pattern

of the nerve distribution within a limb.

For development of sensory nerve endings in human embryos see Hewer (1935) and Hogg (1941); for motor endings see Cuajunco (1942).


By reason of their phylogenetic and embryological origins the cranial nerves are classified into several groups . —

(1) That comprised by the hypoglossal, abducent and trochlear nerves, and the greater part of the oculomotor nerve. The cells of origin of these nerves are situated in the somatic efferent column of the brain stem (Figs. 303 and 309) and their axons are distributed to muscles of presumptive somite origin. The somatic efferent cranial nerves are homologous with the anterior roots of the spinal nerves.

(2) That comprised by the trigeminal, facial, glossopharyngeal and vagus nerves together with a small component of the oculomotor nerve. The accessory nerve also probably belongs to this group. The motor fibres of these nerves have their cells of oiigin m the general and special visceral efferent columns, those with their origin m the former are distribute to peripheral autonomic ganglia of the head region which in turn send fibres to visceral muscles and glands. The special visceral efferent fibres are distributed directly to the musculature 0 t e pharyngeal or branchial arches. Their

fibres terminate in the general and special visceral afferent and somatic afferent columns 0 brain stem. These nerves are distinguished by the fact that their motor fibres leave t e cen ra nervous system dorso-laterally in relation to the points of entrance of their sensory fibres.

(3) "The nerves of special senses . —

(a) the auditory nerve which is a highly specialized somatic afferent nerve',

(b) the optic nerve which is, strictly speaking, not a nerve but a brain tract,

(c) the olfactory nerves.

It is convenient to consider the development of these nerve groups separately.

333' — Cutaneous segmental nerve supply of the human embryo


closely than do the IUrd,

The hypoglossal nerve resembles a typical spinal nerve more IVth or VI th nerves; it is therefore convement to describe it first.


Hypoglossal Nerve This nerve does not belong to the prirmtive head region being only secondarily assimilated into the brain stem in higher vertebrates It develops by the fusion of three or four pre cervical ventral nerve roots which are distributed to occipital somites and later to the musculature of the tongue (page 184) The nerve fibres nnse from a column of cells which is directly continuous with the anterior column of grey matter of the

upper cervical cord (Pearson 1939) In some mammals the hypoglossal motor rootlets arc associated with persistent occipital dorsal root ganglia (Fronep s ganglia) but in man these ganglia if present at all are transient and normally disappear earh in development The hvT»glossal nerve passes to the developing lingual musculature by way of the cpipencardial fidge and here u is closely associated with the upper cervical nerves with which it establishes



a plexiform connexion (Figs 335 and 336) In its course to the tongue the hypoglossal nerve passes lateral to the Xth cranial nerve, the anterior cardinal vein and the branchial arch arteries (Fig 218) With the development of the neck the nerve comes to he at a progressively higher level (cf Figs. 337 and 338), sliding up in the tissue plane lateral to the mam neurovascular bundle of the neck The evidence for the existence of proprioceptive fibres in the hypoglossal nerve is conflicting (Boyd, 1941). Ganglia of the Froriep type are not normally present in the human adult, but Pearson (1943b) has described sensory cells on the intramedullary course of the hypoglossal nerve in the human embryo.

Abducent Nerve. This is a somatic efferent nerve which arises m the basal lamina of the metencephalon (Fig 303, G) and passes from its ventral surface to supply the postenoi of the three pre-otic somites (page 360) In its course it passes medial to the branches of the trigeminal ganglion (Fig 335)

Trochlear Nerve. This is a somatic efferent nerve which arises in the somatic efferent column m the posterior part of the midbrain (Fig 309) From here it passes round the

















335 — Dissection of the head region and cranial and upper spinal nerves in a 10 mm human embryo X c 10

mesencephalic ventricle to decussate with the nerve of the opposite side in the legion the tectum and the developing cerebellum It then emerges from the brain stem (Fig 301) and passes ventrally (Figs 335-337) to supply the middle of the three pre-otic The curious course and dorsal origin of the trochlear nerve have never been a '

explained In its intra-cerebral course the trochlear nerve is closely related to the mesencephalic root of the Vth nerve (Pearson, 1943a) with which it may have un connexions

Oculomotor Nerve. This nerve, m addition to a large somatic efferent possesses a small general visceral efferent component The somatic fibres ave in cells in the cranial part of the midbrain (Fig 309), and emerge ventrally in t e reg midbrain flexure (Figs 335-337) passing to the musculature developed ^ m the

of the three pre-otic somites The general visceral efferent componen _

ciliary ganglion from which fibres are distributed to the unstriped muscu a ur and ciliary' body^



NERVES OF PHARYNGEAL (BRANCHIAL) ARCHES Trigeminal Nerve This is the nerve of the ist pharyngeal arch but it includes as Its ophthalmic division a non branchial component The latter represents the promndus nerve which m lower vertebrates is distnbuted to the apical region of the developing embryo The motor fibres of the trigeminal nerve arise from the cells of the most anterior part of the special visceral efferent (or branchiomoior) column in the metcncephalon These fibres are distnbuted to the musculature which develops in the mandibular process of the 1st arch (Fi^s 335-338) This musculature differentiates mto that of the masticatory apparatus (page 363) The sensory fibres of the Vlh nerve arise chiefly from cells denved from the most

Fic 33r — Dissrct on of the head region and cranial and upper spinal nerves in a mm human embrso — g 00 e bet seen maTiIlarv and fronto-nasal processes /< c 10

anterior (trigeminal) portion of the neural crest but there ma\ be contributions to them from ectodermal thickenings ('placodes; related to the eye region and the ist arch The cells which will form the tngemmal ganglion arc imtiallv arranged as a smaller anterior and a larger posterior group The nerve fibres which arise from the former become the ophthalmic or profundus divasion of the nerve and are distnbuted to the eye and the fronto nasal process The profundus ganglion secondanK fuses with the larger posterior pnmordium of the tngemmal ganglion the cells of which give ongin to exicrocepiue sensory fibres oF the maxillary and mandibular nerves Once the complete tngemmal ganglion has been formed it appears as a massive collection of neuroblasts 'Fi, 334^) situated on the medial side of the pnmarv head vein fFigs 135 and 137; The most sinking characteristic of the tngemmal nerve is







the fact that it has come to monopolize practically the whole of the somatic nerve supply of the surface of the^face (Fig 333)

The mj?S6ncephahc nucleus (Windle and Fitzgerald, 1942) differentiates m the midbram by extepsioif of cells forward from the metencephalon. It appears to be a proprioceptive nucleus for 4 ;he muscles supplied by the Vth nerve and possibly also for the extrinsic muscles of the eyeball. Its cells are peculiar in that although they are primary sensory neurons they are situated m the brain stem and not in peripheral sensory ganglia. These cells are possibly neural crest elements which have become included in the neural plate

Facial Nerve. This is the nerve of the 2nd pharyngeal arch. Its motor fibres arise principally from a nuclear group in the special visceral efferent column of the posterior portion of the metencephalon (Fig 303C) During development, after the fibres from the nucleus have been established, its cells undergo a migration. The fibres between the original situation

of the nucleus and its definitive position consequently pursue a course of some complexity. They pass dorsally in relation to the abducens nucleus, before bending ventrally to pass to their point of superficial origin at the postero-lateral border of the developing pons (Fig. 293). These motor fibres are distributed to the muscles of facial expression which develop in the mesoderm of the 2nd or hyoid arch (Figs. 335-338). The small general visceral efferent component terminates in the peripheral autonomic ganglia of the head region. From the cells of these ganglia fibres are distributed to the submandibular, sublingual, nasal and lacrimal glands This component arisK from a small nuclear group situated lateral to the mam motor nucleus.

The sensory fibres of the Vllth nerve arise from neuroblasts which are close y related initially to the developing sensory neuroblasts of the Vlllth nerve, the two groups of cells forming a single acousUcofacial primordium (Fig 35 ^^)’ primordium is developed in part from ^ e acoustico-facial portion of




mandibular 4








337 — Distribution of the cranial nerves in the foetus (modified from Corning)

the neural

crest and in part, at least m lower vertebrates and probably also in man, from cells by the wall of the otocyst and a small ectodermal placode related to the 2nd arch. t ^ the 6 mm stage the anterior cells of the common acoustico-facial primordium become from the remainder to form a small ganglion, the geniculate ganglion of the facia ip,

334A). The distal processes of the cells of the geniculate ganglion grow out wit fibres and eventually form the major parts of the chorda tympani and greater super cia nerves and the former is distributed principally to taste buds on the anterior tongue (page 184). The central processes of these cells enter the nervous system in the special visceral afferent column (Fig. 303), which in later stages becomes ^g-grent part of the nucleus of the tractus solitarius. There is probably a small soma ic component in the Vllth nerve. , (pigs

Glossopharyngeal Nerve. This is the nerve of the 3rd pharyngea g^gral 335-338). Its motor fibres arise from the special and, to a lesser extent, ro


visceral cfTcrent columns of the anterior part of the myclcncephalon The fibres from the former (which becomes in later de\eIopment the anterior part of the nucleus ambiguus) are distributed to muscles of 3rd arch origin The general visceral efferent fibres arc distributed to the otic ganglion from which post ganglionic fibres pass to the parotid and posterior lingual glands The sensor) fibres of the I\th nerve are distributed as general and special (taste) visceral afferent fibres to the posterior portion of the tongue (page 184) The cells of the superior and infenor ganglia of the I\th nerve which give origin to the sensory fibres are developed from neuroblasts which arc mainly of neural crest ongm but may receive additional cells from two (dorso lateral and epi branchial) placodes developed in the ectoderm overlying the 3rd arch (For an experimental study of the origin of the ganglia of the I\th and \th nerves in Amphibia see \ntema 1943)

Vagus Nerve The \th cranial nerve is formed by the early fusion of the nerves of the last three branchial arches with large general visceral efferent and visceral afferent components which are distributed to the heart the whole of the foregut and Its derivatives and a consider able part of the midgui (Fig


The branchial nerves are those of the 4th 5th and 6th branchial arches that of the yth arch becomes the superior laryngeal nerve and that of the 6th arch the inferior laryngeal nerve (Figs J35-338)

The jth arch nerve cannot be identified m later stages is tt retrogresses when the 5lh arch disappears The central connexions of the superior and inferior laryngeal nerves are similar to those of other branchial arch nerves the motor fibres arising from the special vitceral efferent column and the sensory cells partly from neural crest and partly from dorso lateral and epi branchial placodes (Jones *942)

The sensory cells become the gang lion supenus and the ganglion

nodosum and a few of them send somatic afferent fibres as the auricular branch of the vagus to the skin The 4tli arch nerve also contains a few special visceral afferent (taste) fibres which are distributed to the extreme posterior part of the tongue

The general visceral component of the vagus nerve contains efferent and afferent fibres the former arising from a specialized part (dorsal motor nucleus of the vagus) of the general visceral efferent column of the myclenccphalon The general visceral afferent fibres arise troin neuroblasts of neural crest origin and terminate centrally in a specialized part (dorsal semory nucleus of the vagus) of the general visceral afferent column Cells from the medulla and/or from the vagal neural crest migrate along the fibres of the visceral component to the

Fic 338 — Dutribuiion of ihc cranial nerves u (modified from Corning)



heart, lungs and intestinal tract where they may become the peripheral parasympathetic ganglion cells (page 329).

Accessory Nerve. The cranial part of the XI th nerve is a posterior extension of the Xth nerve. The spinal part of the accessory nerve is of doubtful morphology It may be a special visceral efferent (branchio-motor) nerve to muscles developed from branchial arch mesoderm lying behind the 6th branchial arch (page 363) or it may be a somatic efferent nerve with an atypical course (for discussion, see Straus and Howell, 1936, and Pearson, 1938). It arises from cells in the anterior column of the cervical spinal cord and its fibres leave the cord dorsal to the ligamentum denticulatum and pass up to join the postenor part of the vagal complex before leaving the skull through the jugular foramen (Figs. 335 and 336). Outside the skull the fibres leave the mam trunk of the vagus nerve and supply the sternomastoid and trapezius muscles


The primary differentiation of neurons is dependent on their intrinsic morphogenetic propensities Neuroblasts grown in vitro will differentiate and produce axonic processes in the complete absence of structures to be innervated (Harrison, 1907 and 1935). In the living embryo, however, the direction taken by an outgrowing axon is determined only partly by the inherent polarity of the neuroblast since the nature of the tissues through which the axon grows, the position of the structure to be supplied by the axon and, possibly, the functional activity of other nerve cells, all influence the actual path taken Weiss (jQSQ) shown that the ultra-microscopic arrangement of the molecules or molecular aggregations (tmcellae) in the matrix of the mesenchyme probably has a considerable effect on the direction of growth of an axon, the latter taking the path of least resistance through the connective tissue. The work of a large number of investigators (summarized by Detwiler, 1936) on the development of the amphibian nervous system has demonstrated that the position of the end-organ (effector or receptor) influences, within certain limits, the course of axonic growth. If, for examp e, a limb-bud IS transplanted to a new position the axons which would have supplied it in its oiigma position will, provided that the new position is not too remote from the original one, grow to t e transplant and innervate it If, however, the new situation is remote from the origina one, then nerves from a quite different region of the central nervous system ivill innervate t e transplant. ,

The number of nerve cells which differentiate m a given region of the spinal coi controlled, at least to some extent, by the amount of muscle to be supplied (in the case 0 mo ^ neurons) or by the extent of the territory to be innervated (in the case of sensory neuron^ It IS also, however, controlled by the inherent potentialities of the region concerne the influence of other regions of the nervous system, especially regions at a higher ew .

(1943) has advanced the hypothesis that the growth of the dendrites of aheady 1 neuroblasts is related causally to the initiation of the development of indifferent ce^^ spinal cord and considers that, m this manner, the number of motor neurons is a ^ peripheral load. The relative importance of the different factors on ^ and

nerve cells vanes from animal group to animal group (Detwiler, 19365 ^^nlastic and

m different parts of the same nervous system. The spinal cord appears to be more^^^^^^ more influenced by extrinsic factors than regions further forward where intrinsic apparently, more significant (Detwiler, 1943). Pmtt (1948) gives an what IS known of the causal factors operating in the formation of the nervous sys


The time and mode of onset of function in the embryomc nervous ®^^^^™gyj,g.jnuscular unknown, and what is established relates principally to the development o ^ j j^j 1029) mechanisms. Embryonic behaviour has been studied by Coghill (summanz



urodele Amphibia and contributions have been made on other sub mammalian vertebrates In mammals investigation of the problem is made particularly difficult by the intrautcnne position of the embryo and its dependence on the maternal circulation but the studies of Windlc (1940), Barron (1941) Angulo y Gonzalez (1932) and others on the embryos of lower mammals and of Minkowski (tgzS) and Hooker (i939) human embryo and foetus

have demonstrated a number of important facts though the basic mechanism of the onset of behaviour is still obscure With regard to this mechanism there are two main divergent views one ofwhich considers that behaviour commences as a gcncrahzed activity so that the embryonic reaction is much the same to any adequate stimulus and involves the greater portion of the muscular system This view considers that only later does the muscular response to a given stimulus become restricted to what can be considered to be a reflex The other view considers that the earliest muscular responses to stimuli are localized reflexes and that it is by the gradual mtcj^ration of separate reflexes that the final pattern of behaviour is established The first of these two views considen that a stimulus 1$ perceived as a whole and in relation to the needs of the organism — Learning is held to be an analytical process proceeding from the whole to the particulate (Barron) The second view considers that learning is a synthetic process m which responses are added to a primary set already present at birth (Barron 1941)

As in other organs of the embryo so m the nerves and the muscles there is an earlier non functional period of dev clopment and a later period w hen function is established In the former period the central and peripheral nervous systems develop and differentiate in anticipation (Bareroft 1938) of future functional requirements By the end of this period (which has no fixed limits but varies from region to region of the nervous system and from animal to animal) certain tract systems have been laid down and certain neu ons liave matured to a state where functional activity is possible At the same time muscle fibres have differentiated and primitive motor endings have appeared Functionally the muscle fibres reach a stage of contractility as IS shown by their response to direct mechanical or cicctncal stimulation a short time before the nerves supplying them can conduct impulses (in^ogeme stage of activity) This is followed by a stage (muro motor) in which direct stimulation of the centre or of the nerve trunk causes muscular contraction This ncuro motor stage is m turn succeeded by one (rejiex stage) in which reflex effects can be obtained These three stages overlap to a considerable extent and some investigators (e g Straus and W'eddell 1910) think that the separation of a myogenic stage IS artificial Further the reflex effects are not so localized as they are for a similar stimulus in post natal life

In the human embryo no reflex responses to tactile stimulation are observed before the eighth week (Hooker 1939) Hooker found movement in response to such stimulation in a 25 mm embryo the reaction consisting of a body flexion usually contralateral to the side stimulated with a slight extension of the arms Fitzgerald and \\indle (1942) have also been able to demonstrate that the neuro muscular mechanism is highly excitable at about this stage Hooker found that the tactile stimulation is only cfrcctivc in the skm areas supplied by the second and third divisions of the Vth nerve Spontaneous movements were not observed until the ninth to tenth v\eek Until the fourteenth week foetal movements whether reflex or spontaneous tend to be stereotyped and of the total pattern variety At about this time, however the movements begin to become individualized and the reflexes more localized so that delicate movements can be elicited The movements also tend to increase m


Movements of the human foetus in utero can usually be detected with the stethoscope at about the fourteenth week but is not felt by the mother until the sixteenth

or seventeenth weeks In lower mammals (e g the sheep Bareroft 1946) there is a marked decrease m reflex activity m the later stages of gestation this may be due to relative anoxia or to the inhibitory influences of higher centres as they mature Investigations on the functional development of the brain of the sheep foetus appear to demonstrate that at least in respect 01 respiratory movements and righting and postural reflexes functional activity in the nervous



system first develops m the spinal cord region and then progresses cranialward through the medulla and the midbram to the forebrain.

By the time of birth, and often long before it, the reflex mechanisms controlling such vital activities as respiration, sucking and swallowing are well established (Windle, 1940, and Gesell, 1945). Reflex eye movements are present at birth and the pupillary reflex to light is also established. Minkowski (1928) and Hooker (1939) have described the foetal palmar and plantar reflexes. The grasp reflex is present by the end of the third month, and the Babinski (up-going great toe with fanning of other toes) response to stimulation of the sole of the foot appears about the same time. Minkowski considers that these reflexes are purely spinal until the i6o-mm. stage, but that in later stages they are complicated by the development of function first m the tegmentum and later m the corpus striatum and cerebellum. Control by the cerebral cortex is not established until post-natal life when the pyramidal tracts become myelinated,



The primordia of the olfactory apparatus appear in late somite embryos as two ectodermal thickenings, the olfactory or nasal placodes (Fig. 1 1 o) situated above the stomatodaeum and below and lateral to the forebrain. By the proliferation of the surrounding mesoderm these placodes become depressed to form the olfactory pits (Figs. 106, 112 and 165) (For details of the formation of the nasal cavities see Chapter X.) Further growth of the mesoderm causes the epithelium of each nasal placode to lie in the medial and lateral walls of the upper fifth of the corresponding nasal cavity. At the 17-mm. stage (Fig. 339A) neuroblasts in the olfactory epithelium itself differentiate into nerve cells. These give origin to olfactory nerve fibres which grow toward the apical region of the corresponding cerebral hemisphere In their course the fibres pierce the roof of the cartilaginous nasal capsule (Fig. 339D) which has developed round the primitive nasal cavity and, by the 25-mm stage, begin to penetrate into the apica region of the hemisphere which projects ventrally towards the olfactory placode (Pearson, 1941 } as the olfactory bulb (Fig. 339B) In later stages the olfactory nerve fibres are separate into a number of bundles by the developing horizontal cribriform plate of the ethmoid (Fig. 339D) . The olfactory bulb becomes elongated and eventually the extension of the cavity into it becomes obliterated. Cells in the bulb round which the olfactory terminate and with which they synapse give origin to the secondary olfactory fibres grow centrally and form the olfactory tract which terminates m the region of the pyn or

cortex (Fig. 295). It will be seen that the the olfactory nerves differ from those 0 o nerves m that they are entirely of and their cell bodies remain in the 0 ac epithelium. Some bipolar nerve cel s from the olfactory epithelium and the so-called ganglion termmale whic ciated with the nervus teminalu (Pearson, 94 ’ Larsell, 1950). In lower mammals a spe^i P of the olfactory nerve is distributed to 3 ^ organ as the vomero-nasal nerve. This S’® ?

organ is located in the lower Lgvelop.

the nasal septum. It reaches its u ment at about the end of the fifth organ and its nen-e may £nd m

F,0 339.-F0urs.age. .he development ofUie >■*' “

olfactory nen-es and bulb (after Pearson, 1941) the adult.





The \isual apparatus is dc\ eloped from dnerse pninordia of surface ectodermal neural ectodermal and mcso dermal ongm That part of it which de%eIops from the neural ectoderm appears m earh somite embrjos as bilateral thickenings of the antenor end of the neural plate (Fig 276) which approach each other anteriorly and may fuse The thickened regions soon become grooxed by the optic sulci* (Fig 144) and bulge into the underly ing mesoderm \\ hen the closure of the anterior tieuropore is com pitted the optic pnmordii appear as lateral dnerticula called optic \esides of the prosencephalon (Figs 145 147 288 and 340) If for any reason the early optic plates become too intimately fused across the middle line a single median optic vesicle IS formed and the embryo wall develop into d ^chps wath a single median eye This condition is readily produced experimentally tn lower 'ertebrates (for literature see Adelmann 1936) and occurs rarelv as a developmental abnortnabtv in man (Figs 341 and 342)

Flo 340 —Schematic representation of the antenor aspect of the ptosencephalic and optic v esicles in a 4 mm human embrvo (based on a recorutruction bv Mann t9'’8)

1?^* — Photograph of the head of a lull term c>clops \ iihout proboscis

Fic 34 —Photograph of the head of a full term cyclops ^^Ih a sell developed proboscis

dr.« ^1"'* suggested that the walls of the optic sulci may represent neural crest matenaJ whirh

rs nor lose its connexion ith the wall of the neural lube









At first each optic vesicle possesses a cavity continuous with that of the prosencephalon. The proximal portion of the vesicle then becomes relatively constricted to form the optic stalk The more dilated distal portion of the vesicle is closely related to the overlying ectoderm which

soon becomes thickened to form the lens placode. It has been shown in lower vertebrates that the differentiation of the lens placode is induced by the underlying optic vesicle . This effect is pioduced by a chein ical su bs tanc e (evocator,

■ VESICLE Chapter VIII) elaborated by the cel ls of the vesicle.

At about the 5 mm. stage the lens placode becomes depressed and lapidly sinks below the level of the sui rounding ectoderm. The depress ed placo de is then also converted into a vesicle, the te vesicle (Fig 343), tvhich soon becomes separated from the surface ectoderm (Fig. 344) . During the formation of the, lens vesicle the distal part of the optic vesicle is invaginated into its more pro^'" mal pait so that it is converted into a double-layered optic cup (Figs 289 and 343) which, however, is incomplete inferiorly at the so-called choroidal {foetal) fissure. This optic cup is connected to the prosencephalon by the now' elongate and relatively constricted tubular optic stalk. The ^valls of the optic cup give origin to the lehna and to the epithelnim of the ciliary body and the nu ^ inferior aspect of the optic stalk neai its attachment to the optic cup shoivs a slight groove (Figs. 343 and 345)

IS continuous distally ivith the 0 fissui e on the lower surface of t e op cup. Blood vessels pass into




Fig 343 — Schematic representation of the optic cup and stalk in a 7 5 mm human embryo (based on a reconstruction by Mann, 1928)

cup along this groove choroidal fissure where they .

thickened inner layer, the ens t and the intervening 04,7) The choroidal fissure be narrowed by the growth of its >mtg^ around the blood

II mm. stage mediate

gins begin to fuse in then portions. This fusion rap y pioximally and distally so 15 mm. sWe the foetal is

mally the

mal extension ot the lusiui

and through the

Fig. 344 — Photomicrograph of a section through the developing optic stalk, optic cup and lens vesicles in a 10 mm human embryo x c 88.

M luots s\sn \(


Ii{K oftlic t,r(«\c on thr inferior n {>rct nfthc di'Jnl pirt of tlir ojxic snlk so lint the blood vesuris piomi; into the optic cup lircoinc surroumlctl b> ii«iic of tlie tcmiirnl pirt of the stnlk Non fusion nr pirtnl fusion of the foelil fissure results in i condition known is co)ol)onn (ft 3^B) the iridi il tieficicnes in the omdition is simurd mfeno mednIK

IIisto{;enis!is of flic Ilrtlna llie cells of the tliin ner niit^r hsrr of th e optic cup eirl\ iccpiirc pigment md Iteroine lheyicirrn/r«//r)rr of thtrclini 'riiis then is i |>cnistcnce of 1 pncticill) undinercniiUrt! jmrii »n of llie cpendsiml liver of the ccninl nervous 5\ trni comp-inhle to the thin chnr‘id»l vch of the ventricles I he civit> of the optic vesicle IS non nrcliidnl b\ ilie ip|>oMiioii of its inner hser to the pii^menied liver but fusion of the two I ivers is not intiinite so lint i ixiteninl cleft tlir inttcrtinnl sjner represcntinij ll e oriciml nvitv of the optir vesirle mil hence i jxirtion of the srnt nciiHr system of tlic crnlnl nervous svstrni i>enivls throut;hoiit life 1 he inner liver of tlie optic cup (1 ii,

cm s oon lie iIiMilesl into i tlnrker [vrslerior ,s»

portion the /a/i o//ira re/ie<ir which ilevehijK _ .

into ihe \i ml recejitive |xirtiiin of the iiluli ^

rettm md i thinner interior |wirti tn the o

Iqn (aKfi_jtUrie 1 lie line of jiinrii m / 'k '

Ijctwreri these two reliinl ixirti iin is liter / t/

nnrked liv tlie on Ihe pm cieci /

i j »es not develop nh oto rrreptive l eti^md / y y'

IS sulxiivided m luer devel ipinent into 1 I i

posieniir (iirt the trtin gf mil in I |

inienrir put firinlv fined vvitli the miter I Jf

pi miented I i>er to f inn the / iri HI h irli v \ 'A j

I his list jvrtion i,ridudlv extends vs i

circiilir fririse in front of the (KTiphrr> of *

the lens where it (ornis the |K«tefi« r hver ^ /'/irl *

of the definitive ins I he p m optii i rrtiii le | /<y/ /

undertones liistolomi it ehin^es winch ire j Idji ^ I

es entiativ sinnlir to those iin(lcrt,one bv the / 11 |l \

epitheliiiiii of other iKirtinns of the neuni IR A ^

lulje It consists initi illv of i sini,Ie li>er of colunimr neurit epitlielnim which Mwin itifTercnlntcs into epcnd^mil minile iml

tnirt^iml Iwm Flic rtveiKlviml /one in » . , ■

rnnti/-f I It r •• Jl * niral asitrci of III optic cwi> and Ticial

contict With Ilic outer piL,niemcd Ii>er ifter f ,nm human rmhr>o IhrvrssI, m

Rivin^ ori[,in to die cell of the nnnile zone *• fx-tal f tire till iM-comr tir crniral anert

diiTerentnies mlo the rod mil cone cells «n<l vein of it r mina

"hicli rmv therefore lie regirdevl ns hit,hl>

speenh/cti eprn<l>mil elriuenis lliemimle rone l»ec»>me> thvided into two lijtrs m outer une vthic)i becomes die bipolu liver of die idiili rcnni ind in inner one (ttic optic h)crj •he axons of whicti cxicnil into tlie imr>,iml zone mil th«n Rnivv lowirds tlic ittichment of tlie optic stilk Ihc) extend into tlie nnr>,iml zone of the litter coinerliiii, it into i brim trnct the so^allcd optic nerse The t,rowtfi of die optic nerve filircs into the optic stilk leids to in incrcise m the tliickncss of its wills with consequent obhtention of its lumen Spon^iobhsts tu the intermi hycr of the rctiin md in the optic stilk develop into the j,lnl elements of these regions


7 he lens vesicle Ins usuillv complctelj scpinled from the surficc ectoderm b) the 0 mm 31lA) mcscnchvmc basing j,rown in between ibc two liy tbc to mm stige c lens vesicle is IioIIow md splicricil die will being composed of i single hycr of cohimmr ' u The cells of the supcrficinl half Ijecomc ciilxiidil md their number increises /mi /nssu



with the increase in size of the lens. They form the anterior epithelial lens capsule and peisist throughout all subsequent stages (Figs 347-350) as a simple epithelium. The cells of the deep wall and of the equatorial region give origin to the whole of the adult lens except the anterior epithelium. They become markedly increased in length and project into the lens cavity so that it becomes at first crescentic in section (Fig, 347) and then obliterated (Fig, 349), These











Fig. 346 — Sections through the head of an 8 mm human embryo A at the level ^ eg

grooves, B — at the level of diencephalon, aortic and pulmonary trunks, and trac

elongated cells eventually lose their nuclei and form the lens fibres. The en stage',

from the deep cells form the primary lenticular fibres, to the outer side ffl w ic gf the

are added the secondary lenticular fibres from the equatorial region. T e arra S secondary fibres relative to the primary gives rise to the complicated lamina e


adult Irn Hit n^rv<t!rm\ jmmrJvatrU -»»Ijwrm l«* thr 1<-U» ‘ r‘ '» ‘ ctp'ult*

\ |i fh n \ I'ctilin/rtl m «t« i»>«irn' r ptrt l*s lit** h% alf »1 irtrn i f<ii»«ininii'>n f tnl f f tlif artfn (flhc f<ti! fi«urr n r anlrri'^r put c fihT «p

julr n MVuluJ^nl l'\ tli»’ ^ ^

annul\r nrtrn U7

N( rma^K cuhtu it» n »

rf ifr l'-n« n|«iil'- rrtu** ^

Crrv Ix-f fr liirlJi It p^f

i:'U in ml tin f ri u *f ~ ‘

hirr c! II X «lii.>[ (■^u "'■ < * t* •

1 * -•*'

Mir ,p,fr l^lx rrn llr % A / / 7 ^

pir n f unfirr nf th«- ilr %. u *- *\s -*-■" ^ y ^

^rlrJ n tnii ^n^ i!.r inttrr ^

birr f flhri!r\rl pm • plif >.

cup M tnilnlN firr U in / 7

in\a mill n cT tlir « ptir •>. y

cup till* ipjff jnctnu-i III i

II r anil Cl inrt |r> rr iium a

rciiculitPtl jrlU liVr «,

'lanrr (n^ T|7) viru und ,, ,, v n »t » j o m . n 4 i i fu,'’*l*' bt Juixir

>n ill'- III «] \r\w>li I tncli (imnsiii I n >i <• l r\ l I afeiirl Mann | i 1

Inxr rnirrnl ilir mp tix

ific f iri il (iMiifr Mm M ihr pfiin rcliuin « f tfir Ur ji Aw~ i i r A) j' i/ «r Ulirtlirr It It prirnuilv if rct<«Icntnl nr inrv>!rimtl in iii • tiill in (!i putr Inn tnrxixirrtinl edit iind lul tnlU n titrd'utr In it iti t itrr u < o I lie Miirt ut liiinn iir it riifl'w! li\ t llun l"al 1(1 mrinltfuir nud ut rrnir-il [urt tt pnml l»\ t « m»l which c n\r\t ihr h\ il nd nrtrrv f rwud to the {Knirrt r tiiiftcr « f the lent

ciioKoin setrnA consrA

It lin iliridt liCTfi rtpliitini iImI ihr mint tml optic nme irr ilcrivrcl frnin llir cmlirvornc hmn ind tint tlicir tirtirtiifr lut inulnl ir*rtn!il inert In ihit of Chr idiih hram

  • Miii liomol rin l»p cirnnl furtlirr md ihr c* att <f thr rtrhill rui Ik* conipirrd wiili the

Cf xcrin^t I r (hr hriin I hr nrhrtt intrtlm^ 1 itrr « f ihr hr >m uul «>ptir Clip it tlic nutritive vavruhr emt \»hich Ivci inn the pn trichn'MiI rndunrimixi of the hnin ind opiic nerve llm inter coven llir nil) opiir vrticir mil vthrn tint vrticlr lieroniet inv i:,in Urd to form the « ptic ru|> part if the \ itciiltr roverm^ it nmetl

tviihm ihr cvip In f rm llir inner \ v'cidar emt nrM

to ihr miirr nriinl rriim I he ijniimt,iinted jk r If / / _^^\\ •>"n nljircnt to the piL.tncni livrr of tlic retina

I I I I I I I j trmaini at the tlrnnilivr choniid Ilirte outer and

\ y J j V y J j inner vitciilir nrtt arc rnntinuout at fine over the

y/ alonv, live rntue clvoroHial fwvur

J ^ ® ^ *' — ^ hut liner thnr common toiircc of IiKhkI supplj it

‘u »i 'I'* t*‘r fptulii > f nnrrtt the inner end of tlie fittiire it ii lierc tint the f iurr^"'\_(^lol«tu of I'ulnf I»ennancnl siippl> to the inner vascular coat, tlie t-oma uf vtie i,„ a„ J rj , ,j rrntriil trfinal aiJrr) and ton detrinpt \t the optic









nerve fibres grow back from the retina to the optic stalk, these vessels become embedded in the distal third of the optic nerve and can be seen in the adult entering the eyeball through

the point of attachment of the optic nerve {optic disc).

Soon after the formation of the optic cup and the lens, a condensation of mesenchyme (ectomeninx) appears around the brain, the optic stalk, and the entire optic cup, including the lens. The ectomeninx becomes fibrous, forming the dura mater of the brain and optic nerve and the tough fibrous coat of the eyeball. Between the iridial portion of the optie cup and the skin ectoderm this coat becomes the transparent substantia propria of the cornea while over the rest of the cup it remains opaque and IS called the sclera. In the region of the brain and spinal cord a tissue space, the sub-arachnoid space, develops within the pia-arachnoid, thus separating the pial vascular net on the surface of these structures from an outer delicate membrane, the arachnoid, in direct contact with the inner surface of the dura (page 342)' A similar differentiation occurs along the entire length of the optic nerve. On the eyeball itself no separation of pia and arachnoid occurs and arachnoid space except in the region cornea and ms where aqueous chamber and its flum are comparable to the subarachnoid space and its con tained cerebro-spinal fluib The choroid becomes mar ediy thickened margin of the cup to the ciliary body.

Fig 349 — A schematic representation of the eye of a human foetus of the 3rd month




OF retina \ \

ROD AND \ / \










no subexists, of the








Fig 350 — A drawing of a section through the eye of a 200 mm human embryo to show the differentiation of the parts of the retina and the development of the ins

M KVOl s Msmt

AQVJrou^ rllAM^^n Asn jnis

Hr ifiuo tM rlninljrr in i» \ in th** ns'^rn Iivtii'’ m (t rtl » *■ Oi'- lrfn itul

v-parain it Trt m tl r fr\rrl\in f rn*-* I is jp III'* < ti ili«- intrn r nirfur ol

I'r Irn rp llirliu Ti f rm' if r / » j t I fi«- |>^n} ‘I'-nl r ! »• < f tlir pli tup pm

in <' 1 rrtmtf; i! n lli*' d^*“p «iiif»ir «f llir

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tfr int miiwiil ilur'" I'^r* ^ (J iptrr \l\ !«'■* tf

\ t’l t-frf)ifil pi t « ! Ifi'- I I, itl\r\ n »-Mi! inr » li li r rrif ' fi r I f \ || *• | »rt m ‘i rrn I «-»l*

(* n c > f nil tfi- p i| I \ un iM | m f i*i»- 1 1 1 <* « 

rl 1 i'»-r tl »■ I »> '■n r r*, iniVi t* rn rxtrti • r«-ii ' | , i j,j r i \ — j f -r

l' '■ im u I l! r I Hi ( In- j irf * if »■ i j ir , h ,r j , » K k .

arirririill^ieiifru I’rurf f ft f il ^

In I* I ml i' ^rf , tl I* cinPtu nm tul t I r,V. ' ti jw-i i trnt iii,ilhr\ nnr' r u ••

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n '■ i^rM m ^ i! f u 1 \ t* /• • r f l/Ti 111 I ' ! < ni uniii

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ft' n Tif <“«■ f 1 1 1 1 t } 'h tl I in It It u I III « 't 'Ji" I I '»»»» ’« * '■

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I| |i If rl, t i.ailil. <• rntl I I'l I r-i lUi r Ifrifml full intl

' I' rr itni iiiiri I'li- r ! < irvrl | tt> « ,ii 1 ii i uii • « ff } n I'" H’lt luir' in tfirr pt tl r Ititr tut nit (!ii| ri \S It in ■ |r u J l u I j I >ir .}r\ rl j ui tlir rtir'rin fn mr

II 1 1 'rtj « itfiili ifir 1 1 |i

I fir 1 It— (' •> in It )l il ifir , mm it 1 r is > niiitilirr I III ill ' III] rpi llirliitliil |j m ifir iipjirr Ulil nlrr ( )|t I tfir i rijiiti tiv )l

II I I t ,1 I Imr iiif rr ur

III iiiiiliIxT liT mr firinrlirtl mi rM-rituilI' I unli/r«J i

i nil ui iriiiiiu' vltnii "tiiifi (liMfiin.i't luniinl Ifuiii iriti ifir r injutiriiv it s u liN i lumi l>rr I ( trj) ir ilr cliictuin Hir I irrmi it runliciili irnr n mini rpitfirlnl iiinft wtiicli irr situ itrtl III ncfi rvrluf iinrj,in nrir III mftfn! rxlrrmit> Ifie c'unliciiliis of tfir Inwrr liif n sitintrti mnrr Iiicnll> tfnii tftAt uf tl\C lipJKT litl -Mui in swlisrrpirnt st iL,rs tfic pirtinn nf tfir Itmrr (kI nirdnl In it tl't, 3 jI tlifTcrmti it« into tfir i irimciihr rri,i(»ri intf tfic plicn trmiliimris I lie two cimficiili ^,rit" inciinlK and fmc nitfi -i solid cpnfirlnl conf nfiicli



develops m the line of junction between the maxillary and fronto-nasal processes. Later this cord becomes canalized to form the lacrimal sac and naso-lacrimal duct which opens into the inferior meatus of the nose (Fig. 352)


Each internal ear arises from an ectodermal thickening, the otic placode, ^vhlch appears on the side of the developing rhombencephalic region in embryos of about seven somites (Figs. 97 and 120). In later somite stages (Figs. 99-102) proliferation of the surrounding









\L '











\ j

' 'V.N TO POt»Ti ampulla



-U • cochlear


VESTieULO f cochlear


\ s _s!m tosaccULAB




endolymphatic post SEMICIBCULAK

UTRICLE SAC _ C**' ' - \ - 7 ,. /]



r' '


















n\ ^ late SOIVll*^

Fig 353 — Reconstructions of stages in the development of the labyrinth (after Streeter, 19 ^ ^ ^

10 353 — ivcLLiiisirueiioiis oi stages in me aevciopmeni ui luc ...... ,

embryo, X c 30, B — 9 mm , X c 30, C — 13 mm , X c 40, D — 20 mm , X c 5,



mesoderm elevates the ectoderm around the placode so that the latter non appears as the otic pit or depression B\ the 30 somite stage the otic pit becomes separated from the surface to form the otic v esicle or otoc\-st (Figs 103-iOj) The otoc>st is related antcro mediallj (Fig 334) to the acoustico facial portion of the neural crest to which It contributes some cells The resulting collection of neuroblasts is the primordium of the acoustico facial gang lion (Fig 353 \) The geniculate ganglion of the facial nerve soon separates from this leaving the primordium of the acouslic (itslibulo eochUar) ganglion (Fig 353^) the cells of which remain through out life in the bipolar condition Tlieir distal processes arc distributed to the specialized sensor) areas which develop in the epithelium of the derivatives of the otoc>st their proximal processes grow into the region of the rliombtc lip (Fig 301) Soon a hollow diverticulum appears from the medial aspect of the olocjst and becomes elongated to form the endolymphatic sac The otoevst itself b) diflercniial growth of its walls, then becomes markedly modified (Figs 353 B-E) to form the ulncle semicircular ducts saccule and cochlea

The otocyst is first constricted into an upper vestibular pouch and a lower cochlear pouch From the former three flattened hollow plates at right anj.les to each other become elevated to form the primordia of tlie superior posterior and lateral semicircular ducts The walls of the central portions of each of these ducts come into apposition and become absorbed (Fig 353 ^) so that rims ace left as the secnicvccular ducts (Fig 353D) The superior and posterior ducts share a short common caudal portion the crus commune The lower part of the vestibular

pouch into which the semicircular ducts open becomes the utricle The cochlear pouch soon becomes div ided into an upper portion the saccule and a lower portion which elongates rapidlv and becomes curved to form the cochlea (Fig 353 C-E) In later stages the communication between the saccule and the cochlea becomes narrowed to form the ductus reumens and still later that between the saccule and utricle in the region of attachment of the endolymphatic duct becomes con stricted to form the utnculo saccular duct These derivatives of the otocyst constitute the membranous labyrinth

Histogenesis of the Internal Ear The otocyst and its derivatives are initially lined by a single layer of epithelium but while the changes which have just been


human embryology







portions of ns” thickened epithelial are d

(cnSa ;/ '“if f

if?- ;f

receives a eo specialized areas

sr fi X

TU auditory nen^e (Fi?.

353 )■ The differentiation of the mem

eZZ " p---- -d z;

become 7 ^ dense and it

rPiTo « ^he otic cartilage

Figs. 356 and 357). With increase in size of

carf Hbyrinth the adjacent

cartilage becomes dedifferentiated to form oose periotic tissue. In the periotic tissue rroun ing the cochlea at about the 50 mm age ( treeter, 1917) a tissue space appears adjacern to the pnmordium of the spiral

1 355 ®)? and soon extends along

the whole length of the cochlea to form the ^ca a tympani At about the 1 00 mm stage ' 355G) a similar space appears in

re ation to the opposite surface of the cochleai canal. This also extends along the full ^ cochlea as the scala vestibuli and

It becomes continuous ^\nth the scala tympani at the apex of the cochlea to form the helicotrema. The cochlem duct itself is now usually called the scala media and its irall in contact with the scala vestibuli becomes the vestibular (Reissner’s) membrane. The thickened pnmordium of the spiral organ which IS adjacent to the scala tympani differenti infn +1101 VitrrVil fr oil • 7 firl

jTUBO tympanic

'“S' ■” ■h'

mesenchvmal condensation



epithelium of




ext auo meatus



••'.'AVI ' . •

malleus ’ • ’ .


tubo tympanic' recess

wmcn IS adjacent to the scala tympani differentiates into the highly specialized receptive organ of Corti (Fig 355D), The periotic spaces gradually extend round the saccule to form the sacculat ctsterna and, much later and incompletely, round the utricle and semicircular ducts. The maculae of the ^ saccule and utricle and the cristae acousticae

differentiated to form sensorv k semicircular ducts become highl)'

(perilymphatic) spaces commu ^ ration organs. Eventually the mesodermal periotic

me cochlea (Fig. 35a) pQ„ with the subarachnoid space by way of the aqueduct of

ast and Anson, 1949. ^ account of the development of the internal ear, sec

Tig 356 in the d^veloD ^ than

tympanic recess and tubo and associated structures




The mtcrml nr difTcrs in us ph\lcK;cnciic lii5tor> and m itsnncjin from ihc middle

but the t%so Trt,ions Iwcomc tpprii'tvmtlcd dunnt; llieir development and form a functional

unit The internal car uas oriqinallv an rqan conccrncii v\itli cquilihratinn m hiqher vertebrates it adds to this function the perception of sound In air breathing \erte brates the latter function has necessiialetl the establishment of a special transmitting mechanism to comcv the air vibrations to the interna! ear and this mechanism is situated in a diverticulum of the pharvnx the irtdd t ear or l\tv{a’'u’n In marnmaU the s)und transmuting apparatus is developetl from cartilaqes which in lower tvpes form the articulating Ixines of the jaws Ilirsc Ixines arc part of the ist and and visceral arch skeleton (Chapter \ 11 I>

I he tvnipaniun and the pharvn^otvmpinic (auditorv; lulie are denvesl from the tuliotvmpanic recess (lii,s which (Chapter \) is fonrved clueUv b\ the 1st cndodermal pharvnqeal pouch but receives (I rarer 1014) small contributions from the dnnal portions of the and md 3rd cndodermal pouches ind the inierveninq phar>i«;eal wall (Iiqs 180 anil a oj Ihe external audito') meatus represents in part the isiectodennal cleft I he area of contact fiqs tfi4 and i8j) oftlie latter with thcendoderm of the tulxvivnipanic recess Iwcotnes the ijmpanic membrane mesoderm lieint, soon interposed between the two epithelial lajcrs 1 he externa! car arises from a nunilicr of ectodermal hillocks which surround the opening of the ectodermal cleft (CIiaptcr\ il) Tlie dorsal ends oftlie ist (Meckel sj and 2nd (Reicherts) sisccral arch cartilages lie ventrolateral to the developing labjaanth The dorsal part of Meckel s cartilage is situated in the first arch branchial mesoderm cranial to the tubo l)anpanic recess while the corresponding part of Reichert s is in the second arch caudal to this recess (Fig 183) From the dorsal free end of ^(eckeI s cartilage a small condensation Ixicomes separated to form the rudiment of the incus

i>tnpinic rrresv #n J awociair i ilruriurn

Fir 359 — Scliemc of ihe final slaqe in the (levrloptnent of ihe middle car easily and external auditory meaius

This condensation probably corresponds to the quadrate of infra mammalian vertebrates \ little later the rudiment of the malleus also becomes separated from the 1st arch cartilage ind that of the stapes from the upper end of the and arch cartilage (Fig 357) The nd arch artery as the so called stapedial artery (Fig 183) pierces the stapedial condensauon







Fig. 360 — Photomicrograph of a coronal section through the head of a 60 mm human foetus to show relations of developing ear apparatus x la.

accounting for its two crura. In the human embryo, however, this artery soon disappears. The medial margin of the stapedial ring extends towards the lateral wall of the otic capsule where it engages m an opemng, the fenestra vestibuli, which develops in that wall (Figs. 354 and 358). The malleolar condensation sends a process downwards between the layers of the tympanic membrane. The cartilaginous rudiments gradually ossify and develop their definitive shape and connexions. A small striated muscle, the tensor tympani, is attached to the malleus, and a similar, but still smaller one, the stapedius, is attached to the stapes. They are derived from the ist and 2nd branchial arch mesoderm respectively which accounts for the nerve supply of the tensor tympani from the mandibular division of the Vth nerve and of the stapedius from

the Vllth nerve.

Expansion of the endoderma! mucosal lining of the lateral portion of the tubo-tympamc recess results in the formation of the tympanic cavity; the medial portion persists in a less dilated condition, but becomes gradually elongated to form the pharyngo-lympanxc tube (Figs. 359 and 360). The formation of the tympanic cavity results m its epithelium gradually enveloping t e ossicles, their tendons and ligaments and the chorda tympani nerve so that all these structures receive a more or less complete epithelial investment Later expansion backward 0 t ^ tympanic cavity gives rise to t ^ tympanic antrum and, eventuallyj

istoid air cells.

The external auditory meatu lepens by active proliferation oI its toderm forming a temporary epi elial plug (Fig. 360) '^hich

eaks down m its central por ion

le tympanic membrane, whici icomes partly surrounde Y ig-hke membranous i

e tympanic bone (Figs. 357 ’

issesis a superficial ectodermal layer,



a deep endodcrmat laNCr and iictwecn lhe<e a Ia>er of mescnch\ine \shich constitutes its trmbrara pnpna Tlie upssard expansion of the tsTnpanic caxitN causes the chorda umpam ncr\c to be included within the lavers of the membrane (1 15s 184 and i8j)

Durinq the later months of foetal life the endodcrmal mucosa of the U-mpanic ca\its becomes i;rcatl\ thickened and oedematous so tint the lumen is almost obliterated The cants is aqam established shortls after birth in association with the clnnqes aecompanxing the onset of pulmonary respiration


\natomicall\ and phssiolotpcalK the autonomic nersous sptem can be subdisided into (thoraco lumbar) and patas-impalhtlie (cranio-sacrab portions


At about the 5 mm stage (Fi!* 274D-F) cells are found migraimg along the anterior primir> rami of the thoracic spinal nerses and leasing their medial aspect to pass to the region immcdiatcl> behind the corresponding dorsal aorta ssherc the\ form the primordium of the ss-mpathetic

Tic 3^ —Scheme ol ihe raim com munieanies and of the post ganshon c Rbm m the s>'mpatheuc nervous t)stem Pmc gsnglionic fibres are m solid black preganglonic fibres are m red

nervous system The precise orifin of these cells is still in doubt Most experimental embr> ologists (NIullcr and Ingvar I93 van Campenhout 1930 Harrison 1037 and Y nlema and Hammond 1947) consider that thev are derived from the neural crest (Fig a8o) Others however for example Runt/ (1934) believe that the> are derived bj migration of cells from the

neural tube along the anterior root an opinion which is supported bj the arrangement of the

adult connexions of the svmpalheiic svstem The

two vaevvs are not irreconcilable and according to either of them the svmpathetic nervous s>stem is of ectodermal origin The sympalhtuc rmrobtotr first appear in the thoracic region of the embrjo where they soon form (Fig 361) continuous columns with segmental enlargements dorsal to the dorsal aortae From the thoracic region each column extends cranially and caudally along the corres ponding dorsal aorta into the cervacal and lumbosacral regions rcspccuvel) These cranial and caudal extensions mav also be reinforced by migration from the cervical and lumbosacral nerves Some of the sympathetic cells migrate beyond the dorsal aorta chiefly in the region of us maul branches towards the developing heart lungs and gastro intestinal tract These cells become the prt-aoTtic and usceral sympatkelu ^an^ha and 4 Ccordin£ to some workers the cells ofihe myenteric and sub mucosal plexus of the gut wall The mam relro-aortic columns of celb which



retain their primitive segmentation in the thoracic and lumbar remnnc fnrm i r

.W Nerve fibres (pre-ga„ghc„ic), W becormJdSd;

Figs. 362 and 274F) from the thoracic and upper lumbar spinal nerves These fibres ha“ their cells of origin in the general visceral efferent column of the thoraco-lumbar segments

It shLld be^ noted" thT”"'"'^'" by synapses on the developing sympathetic neuroWasts, should be noted that some of the pre-ganglionic fibres extend to higher and lower

sympathetic chain, i.e., to cervical and sacral regions, before synapsine coel bjond the sympathetic chain to the pre-aortic ganglia, such as those of the

coehac, superior and inferior mesenteric plexuses. The bundle of fibres passing from a spinal nerve to the sympathetic chain is known as ^ pre-ganghomc ramus (white ramus commumcans).

^mpathetic ganglion cells are called posi-gangliomc fibres and they remain -medullated They may pass to other levels of the sympathetic chain, or they may extend

anteriorly, as visceral branches, to the developing heart, lungs, intestinal tract and renal system or, finally, they may pass to spinal nerves whence they are distnbuted to blood vessels, sweat glands and musculi arrectores pilarum In this last instance the bundle of nonmedullated fibres passing from the sympathetic chain to a spinal nerve is known as a giey ramus commumcans (post-ganglionic ramus) (Figs 274 and 362). Occasionally sympathetic ganglion cells are found along both grey and white rami as the so-called “m/ermediate ganglion (Wrete, 1935, Boyd and Monro, 1949) That the sympathetic nervous system may be regarded as fundamentally of segmental origin is shoivn by the presence of segmentally arranged enlaigements throughout lift in the greater part of the length of the chain, by the intimate connexion of the pre- and post-ganglionic rarai to the segmentally arranged spinal nerves, and by the segmental distribution 0 pre-ganglionic fibres to the adrena medulla (Young, 19395 HiHarp, 1947) and of post-ganghonic fibres to the skin (Guttmann, 1940)*








section through the region of the . & 5 and m a 26 mm human embryo

A medullary (pre-chromaffin) tissue

X c 45


The ectodermal cells which migrate to the sympathetic chains do not all become

  • -bem develop into the neurolemmal cells of the sympathetic post-gang lon

hbres and others undergo changes which result in their becoming pait of an extensive ^ ^ o ce s, wit characteristic histological features, which produce the hormone adrenalin. ' latter cells arise from elements in the sympathetic system which are identical in appears with the sympathetic neuroblasts (Fig 280) and they are, therefore, c^\\edpara-gangltomcci^^ s they become stained in a characteristic fashion in the presence of chrome salts they . ca ed chromaffin cells The chromaffin cells differ from sympathetic neuroblasts in t at, their development, they do not produce fibre processes, but they resemble the sympam



cells m tint thc\ ire supplied with nerve impulses from the centnl nervous s\-stem bv pre t;anj;lionic inedulhtcd nerve fibres ind in thit the honnone tbev produce (iilrcinlin) is similar in if not idcnticil wiOi the neuro-humor {yfmf'afhn) produced it the termmition of the post t;an?lionic svTnpitlietic filires

Cliromilhn cells ire widely scitleml in the embryonic sjmpitlictic nervous svslcm riiev ire found m the svmpitlictic tjin^ln m the \iscenl svmpitlietic nmi md in lirqc numlien related to the mtenor surface of the ilHlommil lorti {1 iq '’Ji) v\ here thev form tl c so-called ab'^ominal parai^anjia of /uckcrkandl The main group of cliromalTin cells however and the onU one that nnrmallv persists into nhiUhre is developetl in relationship m the coelomic epithelium of the posterior abdominal wall medial to each gonad where the coelomic cpitlicbum and the para ganglionic cells together give origin to the suprarenal glands


The suprarenal glanils of higher vertebntrs are formed bv two prunordia of diverse origin ectodermal and mrsodennal which liecoiiic rrspectuelj ihe m/dulln and the corUx of the adult glands (I ig 3^3) 1 he cortex of the huimn suprarenal gland develops from rnlumnar

mesrthf lial cells situated on the {Kwlertor alxionunil w ill in the angle lietwccn the root 01 the mescrUcr^ anti the developing gointl Ihcsc cells liegin to proliferate at iIkuiI the 0 mm stage (Loiila inpO formin^ i miss «»f cells which soon sepantes from the coelomic rpi thclium (0 n j mtn ) (I i^ "jn \) anti lirromes difTcrentiated into large acidophilic rells lo tins IS added* at alxiut tlic I2 mm stage a further mesothcha l prolifera tion oinsistm^ o smaller cells which swin spread over the surf ice of the original mass I he smaller cells vmII become those of the ^ nh * t^tx wlnbt the initial p ro liferati on bec omes the so ca lhal Jiital o r pnmxlT t cor tex winch retrogresses ifter birth

■sympathetic crib ippear tin the medio dorsal aspect of the primitive cortex ai tbc^i mm stage and commence to invade it at almut the 14 mm sta^c ^Ii^ jhjj lb the '»(» tnm stage thev fonn a cell group 1 1 ig 30j> «m the medial aspect of the extensive cortex thev irc however not compleicb encapstilited b> the cortex until much later 1 lie> show the (homajfm reactitm at iliout th e *>’^nd week atlrenahn can be identified much carhev ^tatlLSscrl. Keene md Hewer ttr?) but in th e humin foe tus IS not pres ent m high conccmrat ion until i firr Itirij L

  • Tlie iocial suprarenal is relatively very large digs afifi and 2C7), its sire being due to the

extensive development of the acidophilic inner corticil cells ffoctal cortex nr \ ron c^ Onlv the outermost layer of the foetal gland difTcrrmiitcs into the cliaractcnstic basophilic po st natal cortex The foetal cortex insnlmes raptiUy -- »fii-r_liirth so that the plant! b e comes ac uTaftv as well -vs rclitiveb sma ller T he foctil cortex, contains in milro^jCjiic-liormonc but its possession of cortm has not yet been established


The pre ganglionic fibres of tlie crannl pirasympithetic nenous svstem arise from cells m the general visceral efferent column ami pass out in the oculomotor facial glosso pharyngeal and vagus nerves The post ganjionic fibres insc from nerve cells the origin of which is still in doubt Kunt? (1934) considers that the pirasympithetic ganglia m the head region 3^5) lire derived partly from the trigeminal nerve and partly from the cranial nerves

I ic 3<‘j —Diagram to tlio v il e p ilions of Ihe cran at paraiympaiheiic ganglia m r lation to ill cran at n r\o (I a «1 on a figure l\ Kuniz iq3})



conveying the pre-gangliomc fibres. Others (e g , Stewart, 1920) consider that the cells of the ganglia arise exclusively by migration of cells from the central nervous system along the course of the pre-ganglionic fibres Yet others (eg, Cowgill and Windle, 1942) believe that they arise exclusively from neuroblasts which migrate from the Vth, Vllth and IXth (inferior) cranial sensory ganglia Yntema and Hammond (1947) state that the ciliary ganglion can arise independently of the trigeminal ganglion

The origin of the post-ganglionic cells associated with the general visceral branches of the vagus nerve is also in doubt Some investigators consider they are derived from the sympathetic nervous system, others, from the vagus. The experimental work of Jones (1942) strongly suggests a vagal origin for these cells. In chick embryos from which the hindbrain had been removed at an early stage the intrinsic cardiac, pulmonary, oesophageal, gastric and upper intestinal plexuses failed to develop. Conversely, removal of the sacral region of the cord at an early stage resulted m absence of the intrinsic plexuses of the eolon, indicating that neuroblasts from this region of the cord migrate to the lower end of the intestinal tract. Keunmg (1944, 1948) has suggested, however, that the autonomic nerve plexuses of the intestinal tract differentiate from the surrounding mesenchyme. Faulty development of the enteric plexuses may result in one or other of the forms of congenital disfunction of the gut musculature (e.g., pyloric stenosis, idiopathic dilatation of the colon).


There is some evidence (Goormaghtigh and Pannier, 1939) that a few parasympathetic neuroblasts may differentiate into cells of the internal secreting type. These cells are nonchromaffin and may secrete acetyl-choline.


The carotid body first appears (Boyd, 1937) as a condensation of the mesoderm round the 3rd branchial arch artery This condensation is supplied by branches of the 3rd arch (glossopharyngeal) nerve Neuroblasts migrate along the nerve fibres and reach the condensation where, presumably, they develop into the chemo-receptive cells of the mature organ Similar structures are developed in relation to the 4th arch arteries (aortic arch bodies) and to the ductus arteriosus and are supplied by branches of the nerves of the arch concerned Hammond (1941), who studied the development of the aortic arch bodies, considers that the essential cells of these bodies are neuro-epithelial in nature and are of vagal origin The carotid and aortic arch bodies are closely related to segments of the branchial arch arteries which possess specialized pressor receptor mechanisms (Fig 152B)


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As has already been pointed out (page 96 and Fig 94), the embryonic mesenchyme gives origin to many different tissues. One of the most important derivatives is the skeletal system, including bone, cartilage and connective tissue

The earliest known vertebrates had an internal skeleton, the “endoskeleton,” formed by the transformation of the mesenchyme into specialized skeletal tissue This consisted of collagenous tissue in which were embedded small groups of rounded cells It is still doubtful whether this specialized tissue was initially cartilaginous or bony (see Romer, 1946, for discussion) Formerly it was believed that the cartilaginous skeleton was phylogenetically ancestral to the bony skeleton This belief was strengthened by the fact that, m general, the bones of higher vertebrates have an origin from cartilaginous models The earliest vertebrates, however, had extensive skeletons of “dermal” bone and not all bones of higher vertebrates possess a cartilaginous precursor


Cartilage arises from condensation of mesenchymatous cells which form a precartilage blastema in those parts of the embryo where cartilaginous elements later develop The cells of the blastema become round and the intervening intercellular spaces, m which collagenous fibres are apparent, dimmish in size and become acidophilic Soon, however, the spaces become larger, presumably by the secretion of more intercellular matrix by the blastemal cells, and the matrix itself becomes basophilic and homogeneous, while the collagenous fibres cease to be readily apparent In the embryo cartilage may contain blood vessels but in the adult it is usually avascular. The cartilage, except at the joint surfaces, is clothed by a membranous layer of fibrous tissue called the perichondrium Cartilage differs in its structure and properties in different parts of the body. Three chief varieties are recognized hyaline, fibrous and elastic

Hyaline cartilage is found extensively in the developing embryo where it forms mode s for most of the bones (see later) In adults it is found on the articular surface of bones at synovial joints, and in the costal and the larger laryngeal cartilages

Fibrous cartilage has a greater proportion of fibrous tissue in its matrix and fewer carti age cells than hyaline cartilage Fibro-cartilage is found in the attachment of ligaments an tendons to bone, m the intervertebral discs and in certain joints, e g , the menisci of t e nee joint.

Elastic cartilage resembles hyaline cartilage, but has m its matrix branching elastic res It is found in the wall of the pharyngo-tympamc tube, the epiglottis and the smaller aryngca cartilages.


Bone development is usually described as occurring by two membranous (in membrane) and endochondral (in cartilage) — but in each case e process of bone deposition is similar. Indeed, if by origin is meant histo ogica 1 there is no difference between cartilage and membrane bones, the bone- ormin identical in each case (de Beer, 1937)




1 INTRAMEMBRANOUS OSSIFICATION This IS the simpler t^-pc of osteogenesis and probably the more primitive As in the formation of cartilage the first indication of membrane bone formation is a condensation produced l>\ multiplication of mesenchimal cells to form a membranous mass rnade up of smaller more spindle shaped cells than those of a precartilage area The cells lie parallel to each other and are compressed to form crthcr smooth membranous sheets which mav be \ er\ extensiv c as m the blastemal v ault of the cramum, or irregular membranous condensations as in the region where the maxilla will be laid down In further development intercellular collagenous fibres arc deposited the mesenchimal cells of the condensations m the same manner as occurs in the formation of such membranes as dura mater, ligaments and aponeurotic fasciae In the regions where an ossification centre develops the mescnchvmal cells become arran<'ed m closeh packed hjers of cells now called osteoblasts along small bundles of the

Fio 366 — Schemes to show three stages m the ovsihcation of the diaph>sis of a long bone

fibres Their citoplasm increases considerabi} and their nuclei become eccentncallv located

{% 94)

The fibrous matcnal between the osteoblasts swells until it occupies all of the intercellular space This material is called osteoid before calcium is deposited m it Osteoid probably represents the organic matrix of the bone Very soon after the appearance of the osteoblasts and presumably by virtue of the physiological action of these cells calcium salts begin to be deposited in the intercellular spaces and within the immediately adjacent osteoid These spicules of calcium salts are spoken of as primary bone A noticeable increase in the number of capillancs occurs at these ossification centres This increased vascularity is undoubtedly corre lated vuth special metabolic activity and interchange Later these blood vessels become those ^the blood formingbone marrow which is mvanablyassociatedwith the later stages ofembry omc

^ development proceeds transformation of more mesenchvme cells into osteoblasts occurs and these form more spicules extending m aU directions through the membrane but in the case




</,? .tiB c


-^,0 B



8l ?S. ^ 7









Fig. 369 — Schemes to show two stages in the differentiation of the somites and sclerotomes

ossification which are established in a manner similar to that of the endochondral primary (diaphyseal) centre. When this occurs, a gradient is formed in two directions from the cartilaginous growth centre — short columns of cartilage cells extending towards the epiphyseal centre and longer ones towards the diaphysis. This arrangement ensures both growth m length on the diaphyseal side of the growth centre and increase in size of the cartilaginous epiphysis. Some growth also takes place from the epiphyseal centre towards the articular surface, but this appears to be merely enough to assure the proper modelling of the extremities of the bone. It must also be realized that increase in thickness of the cartilage model, distal to the region of periosteal ossification, takes place by continued transformation of the inner perichondrium into cartilage.

The bony shaft (diaphysis) increases m girth by the deposition (by accretion) of periosteal bone and this is accompanied by absorption of the original endochondral bone of the shaft and the establishment of the marrow

cavity (for details, see Brash, 1934). The epiphysis appears to grow in transverse diameter chiefly by the lateral (peripheral) extension of the

epiphyseal endochondral ossification centre. In later post-natal stages in the growth of bone the mass of cartilage (epiphyseal) between the diaphysis and the epiphysis decreases in thickness to form a comparatively thin plate, the epiphyseal cartilage, which is of the greatest importance for the growth of the bone. At the termination of growth in any particular bone the epiphyseal plate disappears and the epiphysis unites with the diaphysis Detailed accounts of the times of fusion of different epiphyses in individual bones can be found m textbooks of anatomy. The number and situation of epiphyseal centres vary in different bones. In a long bone such as has been described there is always at least one epiphyseal centre at each end, and in some there may be two or more. In some smaller long bones (phalanges, metacarpals, metatarsals) an epiphyseal centre is found only at one extremity, the other being ossified by the extension of the diaphysis to the articular cartilage. In small bones, such as the carpals and tarsals, ossification proceeds from a single endochondral centre until the definitive adult size is reached. In irregular bones, such as the scapula, pelvic girdle and the vertebrae, one or more primary centres occur and usually several secondary centres take .part in the ossification of the borders and processes.

Fig 370 — Photomicrographs of sections

notochord and sclerotomes A. 3 mm. human embryo, X c 245>

B 2 1 mm human embryo, X c. 30.

(By the courtesy of the late Dr Peacock }




As hns been described on pit’c 50, the pnnxial mesoderm becomes orpn.zed inlo somites ^^hlch represem one of the principal mmircsniions of segmentation of the embr>o In the head and tail regions the somites undergo nt>ptcal dcselopment or degenerate In the neck and bod\ of the cmhr>o each tvpical somite soon diffcrcnti-ites (Fig 3C9) into three portions (0 a lateral and superficial epithelial phque the ititraiotte (sec pii,c 371) (2) a lateral but deeper mass the miotome apparently dented from the edges of the dermatome and made up of closely packed fiattened cells The mtolome sshich ssill later become skeletal muscle 'page 335^ (3) a medial and \entral mass the sdaotome dented from the remainder of the somuc and consisting of rapidlt multiplying rather loosely packed mesenchtTnc like cells The sclerotome as will be seen git es rise to skeletal elements connectite tissue cartilage and bone The sclcrotomic cells from each pair of somites migrate medially (Fig 50) until they meet in the middle line around the notochord separating it from the neural tube and from the gut iFig 131) When all the sclerotnmic tissue has differentiated from the somites the notochord lies in an axial condensation of dense scleroiomic tissue which still shows traces of its original segmental origin (Fig 231)

Each mass of this axial sclerotnmic material market! ofTln this segmentation has a caudal condensed portion and a cranial less condensed portion I’radcr (toy? ** shown that

this condensed portion tends to move crannlK until it 1$ approximately opposite the level of the centre of each pair of mvotomes In this central segmental position the condensed portion diflcrentiatcs into the intervertebral di'C • The less cellular caudal portion of each sclerotome fuses vvith the less cellular cephalic portion of the immediatelv succeeding sclero tome to form the membranous or prccariilagmous vcTtebral body (Fig 370 \) In a similar manner more dorsallv and laterally the less contlensed portions form the nevital arches and transverse processes while the denser portion gives rise to the intervertebral ligaments

A pair of cliondrificaiion centres slevelop 10 each centrum and very soon fuse across the midlinc to form the cartilaginous vertebral liodv (Fig 370IJ) V similar chondrificaiion centre forms in each half of the neural arch and eventually extends slorsallv to fuse behind the neural tube with Its counterpart of the opposite side These same centres extend vcntrally to unite with the cartilaginous centrum and send extensions laterally between the inyotoniic masses to form the transverse processes W hilc this is going on cliondrificaiion also occurs m the membranous costal areas to form ribs Somewhat later primarv ossification centres occur in almost the

Fi 371 — Diagraiw If) lUuitiaie itir fution of the lateral cam |j;e elemenu to form Ihe ster num T1 e ribi are thovtTi in supple (after Hanson 1919)

Descnptions of lerirbral formation presious to ihat Riven b> } raJer had uiually staled iliat a lerlebral body was formed by a fusion of the conden ed caudal one half of one sclerotome \ ilh Ihe less condensed cranial portion of the next sclerotome behind and had thus accounted for the alternation of ihe vertel rae v ith the myotomes Such accounts were alwa)s inadequate m that they did not clearly show the origin of the inter vertebral discs and ligaments nor did they explain why mrsenchvme of the sclerotomes in the process of chaneinc into hyaline cartilage should go through a process of rapid cell division with decreasing size of cell { condensa^ lion ) in the cranial half of the vertebral Isodies while in the caudal half it proceeded along the usual lines of enlargement of the cytoplasmic area of the cells to form precatwKgc ( ratificaUon )

Praders description of the process is enlircly wnhin the paitem of v hat is known about the listogenesis 0 hyalne cartilage and ofl gamenis and fibrocartiUgc such as that of the intervertebral discs and IigamenU also It accounts satisfactorily for the inteneRmcnialposiuon of th« vertebrae and ihesrRmenial position of the discs » , '•’«*>M“>?fn«'*andde'elopm nt of the micrvertebral discs Before

birth these attain «seni.all> the typical struciurc found in the adult The nucleus pulposus is shown to be formed "oi on'v from the notochordal uttue but also from muco gelatinous degeneralion of the inner ' F>bro cartilaginous disc The blood supply of the discs is shown to be derived from the external vertebral plexus independently of that of the vertebral bodies and lo penetrate generally only as far ax the junction of the outer fibrous ring and the inner fibro cartilage Sec also Peacock ig^i ^ ^



same pattern as the earlier cartilage centres, and long after birth complete the vertebrae. Briefly stated, the notochord degenerates completely m the region of the centrum, but enlarges considerably in the intervertebral regions to form the nucleus pulposus of the intervertebral discs. These latter are fibrous and fibro-cartilaginous rings which develop around the notochord between consecutive vertebral bodies from portions of the sclerotomic tissue which does not chondrify. The other intervertebral ligaments are formed in the same manner.

It IS in the thoracic region, where the costal elements are best developed, that a cartilaginous sternal bar forms on each side connecting the growing ends of the rib cartilages with one another












olfactory N






neural arch




Fig 372 — Diagram of the head end of a 21 mm human embryo to show the cartilaginous skull, cervical vertebrae, and brain (after W H Lewis, 1920) X c 92

(Fig. 371) These bars are brought into contact at the cephalic end of the thorax, as the ^ wall is completed there, and fuse forming first the manubrium sterni, then the sternal body and final y the xiphoid process (at about the mnth week of intrauterine life) In the xiphoid region complete fusion often fails, leaving an adult xiphoid process which is forked or perforate Perforations higher in the sternum, due to incomplete fusion of the bars, are more rare


The skull has a complex developmental history which is associated with its progressive modification in vertebrate phylogeny and with the adaptive specialization of many o its ponents. The ossicles of the middle ear are a good example of this modification an !

tion. Originally, m primitive chordates, they were gill supporting structures, ater, m 1 >


amohibia and reptiles they become part of the jati skeleton and linall) in mammals parts

of them become tL mechanism for the transmission ofsound nates from the

to the cochlea The embriolog, of the skull ts further complicated bj the fact

of the hones ate det eloped in cartiWse {e s , ethmoid), othets m memhnne (e g parietal),

and others hate holh mtramemhranous and endochondral centres (eg occipital and

^'"'*Th'PcanilaLmous parts of the detelopin; skull (cWrecroiiiuml and the bones arising tn them ticre formerlt considered to b e older ph>lo geneticall) than the membranous bones Thus the mammalnn chondrocranmm was compatedwith the pnm\U%e- cartvlagmous s^U of pnmitue \eriebrates which do not desclop ossified inembnnous cranial elements As has been mentioned earlier boweter there is now reason to l>elie\c tint membrane bone ma> well

be more ancient than cartilage bone The membrane bones sometimes called dermal bones of the skulls of all higher \crtcbrates arc regarded as hating arisen from bon\ scales and plates embedded in the skin of the ancestral \criebratcs *

The skull consists of a protective case (the neurotranium) around the brain and of thejatv skeleton (mcerocramum or iplancftnofranium^ In each of these portions a mesenchymatous condensation is the first indication of skeletal formation later the mesenchyme ma^ bero me converted into jnspiljtane (dexm al) bone or into cartilage which m some regions persists throughout life and in others undergoes endochondral ossification

• TVic trtaUoDstnp tjf ibe derinat nsui^rs it» the pb}loSMKaic ongia of the definitive dermal bones has been a matter of cons derable d spute In the true fishes these dermal boies haw: come to supplement the cartilacc bones of the skull yet still remamini; essentially in the skin The conclusion as evidenced also m the most recent works of Severtzoff (19 5I and Moy Thomas (1924) » that membrane bones arise itv topoerapbical relationtoandunde lyingbutnoioutofihedeiitides (deBecr igjy) It may br noted that there are however more of tlcse scaly plates m a fish s skull than there are mraibrane bones m the skull of man This would be in I ne with the well established fart that as the vertebrate scale is ascended the number of bones in the skull is reduced (Wdhston s Law)




The mesoderm which gives rise to the neurocranium is at first arranged as a membrane, the memnx pnmihva, round the developing neural tube Later it becomes subdivided into two «  layers, an inner, endomemnx, and an outer, ectomemnx (Fig 372) The endomenmx is concerned with the formation of the pia mater and arachnoid (page 287). The ectomemnx differentiates into the dura mater and an outer superficial membrane with chondrogenic and osteogenic properties. As has been described in Chapter XII, in the region of the spinal cord theie is^j an epidural space between the dura mater and this outermost layer, but m the neurocranium the layers remain in close apposition except m the regions where the venous sinuses are developing It is from the cells of the outermos t membrane of th e ectomemnx that the cartilage and b one of the neurocranium are deriv ed


In the basal region of the developing skull, cartilage is first laid doivn, but is later, for the most part, replaced by bone The cartilage appears as discrete condensations forming a definite pattern (the chondrocranium) which is strikingly uniform throughout the vertebrates The following regions of cartilaginous condensations m the basal membrane may be

recognized m the human and other mammalian






skulls (Figs 373 and 374) —





V ^ \ ^ 1 \ CAPSU





( 3 )

a parachordal region in close relation with the' cephalic part of the notochord, 1 e., from the region of the caudal end of the hindbrain to the hypophysis

a pi echorda l or tiabecular region m front of the notochord

Fig 374 — Scheme of relations of the parts of the chondrocranium seen from the lateral aspect Neurocramum, stippled, viscerocranium, cross-hatched


cartilaginous sense capsules, auditory, olfactory and possibly optic Parachordal Region. Immediately caudal to the hypophysis m the region of the most cranial portion of the notochord, chondnfication of the condensed ectomemnx occurs to form an unpaired plate-hke mass, at first between the notochord and the brain stem (Fig 375), This is the parachordal cartilage or basal ^ Immediately caudal to this area, between it and the first cervical sclerotome, there are

developed, somewhat earlier, four occipital somites and, from these, three fairly typical sclerotomes (The most cephalic somite is veiy rudimentary and disappears without giving origin to myotome or sclerotome ) The mesenchyme of these' three occipital sclerotomes does not retain its segmentation as m the vertebral region, but instead fuses to form a condensed mass, continuous ciamally wnth the parachordal condensation and laterally iv'ith the ectomemnx and completeh indistinguishable from these except by position. The caudal part of the basa plate thus represents a fusion of thiee or four occipital sclerotomes w'hich have been assimilated into the skull in those vertebrates possessing more than ten cranial nerves. This assimilation makes the hypoglossal ner\'e one of the cranial series Chondrification extends fiom the original parachordal centre back into this occipital region and laterally into the ectomenmx until, at the region of the foramen magnum, it extends dorsally, as the occipital tectum [tectum posterius), completely round the neural tube, like the neural arch of a vertebra. In spite of t le early fusion of the consecutive sclerotomes m this area, some evidence of the original segmentation is retained in the grouping of the hypoglossal nerv^e rootlets into two or three consccutu e bundles which pass through separate openings m the dura mater and occasionally throng 1 •dm'dcd bony hypoglossal canals. Later in the tectal cartilage ossification centres appeal a


2=; mm \%hich become, when thc> fme the supraocapitat portion of the tabular part of the occipital bone i e the portion between the supenor nuchal lines and the foramen magnum

Trabecular Region In the mesenchyme of the basal region on a level with and

m front of the hypophysis cerebri tw o pairs of centres of chondnfication appear The front pair IS the trabeculae crarui* and the other pair is the polar hypophyseal cartilages flanUng the eramo phar\ ngeal duct which represents the tract of Rathkc s pouch In man these four^ondnfica tion centres soon unite and then join with the anterior margin of the basal plate There is now an elongated plate of cartilage which extends from the front of the skull to the antenor border of the foramen magnum The brain rests m the shallow longitudinal groove formed by this plate (.Figs 373 and 374)

Flo 3,5-»-Mcdiaci»as«la.ttcciiontt»rougf\ihrhradcndofa urtim human embryo 10 sho^v the relationt of the notochord to the vertebral centra and the parachordal cartilages ^Based on Bardeen )

In the ectomemnx covering the ventrolateral aspect of the brain two cartilages appear on either side (Fig 373) these are the alaorbitahs {orbilosphtnoid) and the ala temporalis (alisphenoid) The ala orbitalis (orbiiosphenoid) becomes a well marked cartilage which b> two medial extensions around the optic nerve fuses with the cranial part of the basal plate forming the opiie foramen The cartilage later becomes ossthed forming the lesser wing of the sphenoid

(Ftg 3781

The second ventro lateral cartilage the ala icmporaUs lies between the ala orbUaUs and the antenor part of the otic capsule It is pn>babl> denved from an upward extension the processus ascendens of the pierygngjadrale cart lage (Fig 374), although in man it has a separate centre of chondrificanon The exact homologies are still doubtful and obscured b> the

nrm.n “ morphoWical and expenromuJ evidercc tuggatin^ thai vhe VtabecuUe crami have ibeir

"nd (.e; dt a«r ,9,7



appearance of membranous ossification in relation to it in later stages. In man, the ala temporalis forms the greater part of the greater wing of the sphenoid and is separated from the ala orbitahs by the Illrd, IVth and Vlth cranial nerves and the first and second divisions of the Vth cramal nerve. The second division (maxillary) is later absorbed into the substance of the wing and lies in a separate foramen, the foramen rotundum Posteriorly the ala temporalis is separated from the otic capsule by the third (mandibular) division of the Vth nerve and the internal carotid artery. The mandibular nerve is absorbed into the bone and so comes to he enclosed in the foramen ovale.

Sense Capsules. Each otocyst is surrounded by mesoderm which becomes chondrified to form the otic capsule. Each capsule lies lateral to the basal plate and in subsequent development fuses with its lateral margin (Fig. 373). The fusion, however, is incomplete and a foramen, the jugular, is left between the posterior extremity of the capsule and the plate The capsule Itself is pierced medially by an opening, for the Vllth and Vlllth cranial nerves.

The opening later becomes the internal auditory meatus (Figs. 377 and 378). (For details of development of the otic capsule, see Bast, 1930.) A cartilaginous capsule develops in the mesoderm around each olfactory pit (Figs. 372-374). These capsules soon umte with each other and with the anterior part of the trabecular cartilages. The optic or sclerotic capsule is not chondrified in man, although it is in some lower vertebrates, and, in association with the free mobility of the eye, does not fuse with the basal cartilaginous complex.


In the part of the ectomenmx dorsal and lateral to the developing brain chondrification does not occur. The bones m this portion of the neurocranium (frontals, parietals, interparietal__portion of the occipital and" the squamous temporals) appear as intramembranous ossifications. In addition to these large bones of the cranial vault certain smaller bones fringing it, e.g., lacrimals and nasals, also develop in membrane.


The viscerocranium consists essentially of the cartilaginous bars of the pharyngeal arches and it represents the gill arch skeleton of ancestral vertebrates This cartilaginous skeleton, howev’^er, is supplemented and partly replaced by dermal bones The pharyngeal arc

cartilaginous bars develop in the branchial mesoderm, but there is experimental evi encc (page 270) suggesting that they may be denved, in part at least, from neural crest materia (Stone, 1922; and later) Parts of the cartilaginous bars become ossified, parts throughout life in the cartilaginous state, and parts are represented in the adult on V V perichondrium which forms certain ligamentous structures In man the membrane ( ‘

bones which supplement the cartilaginous viscerocranium are restneted to the maxi ary and mandibular processes of the ist visceral arch.
















Fig 376 — Lateral view of a scheme of the elements of the cranium Cartilaginous ncurocranium, black stipple, cartilaginous viscerocranium, black crosshatch, membranous neurocranium, red stipple, membranous viscerocranium, red cross-hatch




-there Ate thcotetvraUv six puts of cartilaginous tods constituting this portion of the developing stull, one m each of the visceral arches These bars first appear as condensations In sequence from before backwards, m the visceral mesoderm surrounding the pnltive fotegut (Chapter X) 1 he dorsal ertremiltes of the first “d second bars of Mch side reach to the under surface of the neurocramum in the otic region (Fig 37 1 folloued ventrallv each of these bars curves aKnmd the pharyngeal wall (lit 370^ m the mass S r corre^oniing arch to fuse with lU fellow in the middle line in the Pha^^

The mesenchymal condensations of the 3rd gth 5* and 6th arches are fo“"d V entral portions of the eotresponding pharyngeal mesodcmaal masses and hence are not inv olv cd

Fio 377 — Dona^ aipfcx rf a inode\ of rl)ond/i>~ F»C 3,8 — Dorsal aspt-ct of a model oT the chondrow craniumofa 20 mm human embrso (after Kcman cranium of an 80 mm human embryo (after

tgiS) V. -ala hYpochsasmatica B— alcocWcar Hertwjg 1906) A — imetnal opening of faual

commissure canal

ttt the deselopm^nl of the chondrocramum The area of mcitnch-^Tnal condensation in the ist arch soon becomes chondnhed and subsequent!) this occurs in sequence in the other arches The dorsal part of the ist (mandibular) arch grons fomard beneath the deselopmg e>c region to the olfactory area This is the maxiUary pro ett and it farms an acute angle open fora ard \s here it joins unth the \ entral segment or mandthulat pmess As a result of the forma lion of this process the mesctichvmatous condemalion which will ^i\e ongm to the ist visceral arch cartilage becomes bent also the dorsal portion being included in the maxilUt) process Part of this dorsal portion m the maxillar) process becomes chondnfied forming a small cartilaginous mass which represents the pU^go qjadialt bar of loner tertebrates (hig 374) The remaining \ entral and much larger portion of the j$t arch me$cnch)-mal condensation m the mandibular process chondnfics to form Meckel s carUlagt The posrenor extremities


can non be recoemaea as the dermilnc cartilassmoiis nidimeM of the maHtm, "Me the t entral portion is imoheii m the aetelopment of the Itntei jats (sec Met) The ptps^quadrate Mrtilat,e itself is the cartilaginous ruaimcm otthe mm •The portion of the and areh car go conuct "ilh the incus separates from the test of this enttitagmoiis bar to form nhich IS interpmcrf betsseen the otic capsule niediaU> and the incus hteralll Us tlM «ch origin IS emphasized bs its relation to the utet> of this arch "hieh passes through the emho onic stapes Ossification occurs m the cattilagmous malleus, meus and stapes in the fourth month of mtrauterine life These arc the first bones to be fulli osiified and to reach adult size (^ce ^n‘'on ft a! 194S)

Tic gfJo — Lawral upect of a model of ihe ikuU of aR 80 jnro human tnibr>o The c{\oT\dtocfamun\»colcnjTtdbli« iHe mMobtaat botiM yellow and the Tla tentpoiahs green (l3a ed on Kem ig» model from Kollinann i Handatlas 1907 I

The portwn of the anti arch catula^c tmmcdwtcl) btlo%\ ihe slapes fusc$ \\Ub t)]e one caphule andohstftes later to form the It la conunuous %Mth the Jt>fo h>oi(f ligartiPiil

u'hich represents the sheath of the and arch CariiUge betv,ctn the st\\onl prcMress and the ifssfr cornu of the Motd bone (Fig 379) The latter together SMth the upper part of the body of the h)Oid bone is the ossified ventral CKwemit> of the 2n«iag of sphcRoidj ^ *



There is some divergence of opinion on the developmental history of the 4th, 5th and 6th visceral arch cartilages. Chondrification does not occur in the dorsal portion of these arches The cartilages are, consequently, restricted to the ventral region ivhere they fuse to form the laryngeal cartilages. The 4th and 5th become the thyroid cartilage, and possibly the 6th contributes to the cricoid. The arytenoid, cormculate and cuneiform cartilages are probably derived from the 4th and 5th arch cartilages


In mammals, as m many other vertebrates, ai cades of membrane bones are laid down lateral to the cartilages of the ist visceral arch and in the substance of the maxillary and mandibulai processes In the maxillary processes of each side there are four such ossifications which form, from before backwards, the premaxilla, the maxilla, the zygomatic and the squamous temporal bones (Figs 376, 379 and 380). Owing to the great increase in the size of the mammalian, and especially of the human, brain, the most posterior of these bones is assimilated into the wall of the neuiocranium and fuses with the outer aspect of the otic capsule which becomes the petrous poition of the temporal bone. On the deep aspect of the maxillary process, and in its tecto-septal extension (p. 180) there are further membranous ossifications which form the palatine bone and the vomer and contribute to the pterygoid laminae

In the mandibular process two membrane bones are laid down on the outer side of Meckel s cartilage. The anterior of these, which appears very early, is related to the lateral aspect of the ventral portion of the cartilage and forms the mandible (Figs. 376, 379 and 380) At first it is a small splint of membrane bone but, by growth and extension, it partially surrounds Meckel’s cartilage (Fig. i8r) except at the 1 anterior extiemity of the latter where some endochondral ossification occuis At the posterior end of the developing mandible there is an upward growth to form the ascending ramus. This portion of the mandible comes into relation \vith the squamous part of the temporal bone to form a diarthrodial (synovial) joint — the temporo-mandibulai articulation — m which a fibro-cartilaginous articular disc develops. The ramus of the mandible shows, in part, a transformation into cartilage before ossification occurs.

The significance of this “secondary” cartilage is not understood, but its occurrence emphasizes the closeness of the developmental relationship between “membrane” and “cartilage” bone.

The other membrane bone of the mandibular process lies lateral to that part of the ist arch cartilage which becomes the malleus. This membrane bone is the tympanic plate and, in later development, it fuses with the squamous temporal bone and the cartilaginous otic capsule

The nasal and lacrimal bones are also developed as membranous ossifications in close relationship to the nasal

  • Specifically sccondan cartilage precedes ossification of the mandibular angle, coronoid

condyle, and in scattered areas of the alveolar process It also occurs in connection with seve bones fsec de Beer, 1937).

Fig 382 — Lateral aspect of a model to illustrate the development o the caudal part of the vertebral column and the interior extremity in a 9 nim human cmbr)o B=scleroblastema of femur and acetabulum X c 22. (This figure and Figs 333-336 are based on Bardeen, 1905, reproduced by the

Fig 381 — Photomicrograph of a section of the forehmb in a 10 mm human embryo Note the thickened epithelial plaque at the apex X c 80



capsule (Figs 379 'ind 380) Tlie% ma\ be regarded as imilar to the membrane bont» developed m the maxillan process but are more mtimatcK related to the membranous neurocranium


In the chapter on external form (page tto) the ongins and earl> growth changes in the appendages have been described From Figs 104 105 tji and 381 it can be seen that the limbs first grow lateralh and that the earliest sign of a joint m each is a ventral bend at the future elbow and knee (clbou at about 12 mm knee at mm CU) Ihe convexities of the bends which correspond to cich other, point dorso-latcrall^ A little later the thumb and great toe develop on the eranial or pteanal border of iheir respective limb buds Thus not Qnl> is the thumb comparable vtifh the great toe but the whole prcaxial half of one appendage with the preaxial half of the other TIic more cranial nerxcs ol the limb plexus mncAate the jkin of the preaxiaJ portion the more caudal ones that of the postaxial (Fig 333) Thus the limbs arc dcvelopmcntallj segmental (see Chapter \I\ )

The first mesench^anatous condensations of the appendicular skeleton are m the region of the future girdles and tliose for the pectoral region appear a little before those of the pelvic region This is consistent with the fact that the bod> of the embno forms and difTercnliates in a cephalo caudal direction Further the mcscnch>mal condensations for the bones of each extremitv appear in a proximo distal sequence although thev are all laid down at a rclativeh earli period (about six weeks of intrauterine life length 12 mm C R ) Tlie details of the limb skeleton development arc shown in Figs 382-3O7 Like all cartilage bones these are preceded b> a membranous or blastema! stage and the centres of chondnfication correspond to the primary centres of ossification which appear a few davs later The pnmarv centres of ossification arc formed m the hrL,er bones as earlv ns the 25 mm stage (eighth vveek of foetal life) Fit, 386 IS from an embrvo of 50 rom

The development of the skeleton of the upper extremu) proceed-* according to the same

Fir 383 — Lateral a<pect of a model 10 it uiiraie »le\ftopr\<-ni of ihr c-iudal part of tfir veriebral column and thr inferior cxtrcmit' in an II mm human embrvo C 16

Fig 384 —Lateral aspect of a model to illus trate the development of the caudal part of (he vertebral column and the inferior ex tremit> m a 14 mm human embrjo A=centres of chondtificawon >i\ the vertebral bod es X c 30

general plan the larger elements being the first to cliondrif> and the first to ossify The one excep lion IS the clavicle which is apparcntlv a mem branc bone Its primary centre of ossification appears dwnng the sixth week of intrauterine life

FlO 385 — Lateral aspect of a model to illustrate the development of the caudal part of the vertebral column and the inferior extremity in a 20 mm human embryo x c 15



before any chondnfication has occurred in the embryo and is the first ossification to take place in the body. Secondary chondrification centres do occur at each end of the clavicle later on, and ossification progresses in them in the general manner of endochondral ossification


The detailed chronological history of


Fig 386 — Lateral aspect of a model to illustrate the detelopment of the caudal part of the inferior extremity of a 50 mm human embryo X c 4

the appearance of the primary and secondary ossification centres of the limb skeleton and of their fusion is to be found in anatomical textbooks It should be sufficient to state here that before birth primary centres occur in all the bones of both extremities except the patella, the carpals and the navicular, the cuneiforms and sometimes the cuboid bone of the tarsus On the other hand the only secondary centres normally present at full term are in the distal epiphysis of the femur and sometimes m the proximal epiphysis of the tibia


From the structural standpoint, joints may be subdivided into two general types —

. (a) Those in which a synovial mem brane does not develop [synarthroses)

[b) Those with a synovial membrane [diathroses or synovial joints).



Fig 387 — Lateral aspect of the skeleton of the upper extremity of a 1 1 mm human foetus (Based on Le\sis, 1902 ) x c 14

connective tissue cells tend to be arranged finally actually secrete a cartilage matrix al

The primordium of the skeleton in the membranous stage is essentially continuous. Individual elements first become recognizable when the precartilage of the chondrification centres appears, or when ossification centres start in the membrane bone areas In either case the residual membrane between these centres eventually develops into the ligaments of the joints. The cells m these areas elongate, multiply rapidly, line up parallel to one another and later give rise to large numbers of collagenous and some elastic fibres. In a few places such as between the vertebral laminae the fibres are mainly of the elastic type (ligamenta flava). In others, such as the inter\'ertebral discs, the collagenous fibres are veiy large and numerous and are arranged in a definite interweaving pattern. In the more central parts o the ring-like fibrous layers of the discs, the rows, and to become lounded or cuboidal and t themselves, thus forming fibro-cartilage.

  • This reminds one of the similar secondary cartilages of the mandible There is some explanation o

membranous nature of the clavicle from the comparative standpoint, as it is believ'cd that the clavicle is, ^ ^ iTi part, a modification of one of the membrane bones associated with the opercular apparatus of the gi *■ Jfc ancestral \ ertebrates


35 »


thc'c arc the simpler ivpe of jmnl ihm devel<>pnwni \NtU »< fini

has alfeids ixrcn stntexl the Ixmes arc ftnt repmcntci} h> condenMlmm of the mtsenchsme svhich later become comerted cither through a canihl,inom snt;e or ihrecth b\ rntnmem br-movMWMricatmn mm the pnmordnof the future iK.nes Hie contit^uous mc'rnchjnntous or

cnrtihi;mom prtmoTtha are roimecteil h) menn* of undiircrentinctl mesench\inc If this mcscnclis-mnl li«iic persists mA htcr fieromes s«tt> fibvsius tsww a% tn lUc sttlutes.

!;et«ecn tlic inemhmnous Ixmn of tJic s lulf of the sKiill the iKmes arc tinitctl ».% fibrous joints uitliout a ssnosnl ca\H' Hiese simple ssTurihrr«et ire eilletl i c union (ssn )

bs a tsand \desmfH) If the tnesenchsmil tissue lietMeen the Imnes lircnmrs rhomlnfictl as for e-sample lietssecn the first nb and stcnuim the joml is referred to as a nref r-'ninj or cartilicttnous joint HiC cartih^mtnis tissue l)ets»een the Ik>is> elemcms mav lieesime ossified at puberts or later «o tint the Ixmei are joined bi m«er«« tissue i r a jirftifuii Ibis tj-pc of union occurs lieiisren the dnphj-sis ami llie epiphsats oflmncs

fio — rtioioniiff I8f*pti of a . fi,>n fad%rt.ptii: Jio jr-lJl - U.M ii. croijraph .fa irclion aUn« at; ml «f s i niin liumao wtrs .r a <lr\fl p,nij tiumrr i-uhur joint of a

^ Oj jj inn\ tinman nvJ n > c a


These joints are usualls formed lirtsseen e3rtdii;e Inmn but ilie cartiht,moiis ixirtions oJ membrane bones mas panicipitc in them Ihere is no indication of the site of the future sjnosial joint until after the differentiation of the cartiht-inous mmlcls of the future lioncs Soon after the cartiht’inous models arc h«d doun the inesenchsme hcUscen tlic emU of adjacent cartihi?.nous elements becomes arnni,ed to form a jotnldtsc (ll^ 308\) In thcccmrc of the disc the cells arc fiaiicned sshilc at the per,p!ieT> lhc> arc continuous iwth the penchondniim of t he cartilaginous models The gross tli of the camlaipnous elements ton ards each otlirr Compresses itecmualp-.,, „t,tejo,md„c nnd u ll,c ,imc time , cim,> ,n iI.c arc, mfcrcnMl

pm The crih m the cenlrr the ,l„c soon d,„ppc„ ,|nl rl,c cwnhuc okmonu comn mlo coniac. „.ih o™h olher and for a „me there nnj l,o a ,l.r„t carlihi,mo>n umon Tin. carnlago funon „ .„y transMon and docs not m.oKc ihc fall area of ,i,c articular surface nor do the cell, pan irr the frr.rrm diffctcmnlr imo Irjahnc carlllage cell. Soon lire



before any chondrification has occurred in the embryo and is the first ossification to take place m the body. Secondary chondrification centres do occur at each end of the clavicle later on, and ossification progresses m them in the general manner of endochondral ossification elsewhere.

The detailed chronological history of


Fig 386 — Lateral aspect of a model to illustrate the development of the caudal part of the inferior extremity of a 50 mm human cmbrvo X c 4

the appearance of the primary and secondaiy ossification centres of the limb skeleton and of their fusion is to be found in anatomical textbooks. It should be sufficient to state heie that before birth primary centres occur m all the bones of both extremities except the patella, the carpals and the navicular, the cuneiforms and sometimes the cuboid bone of the tarsus. On the other hand the only secondary centres normally present at full term are in the distal epiphysis of the femur and sometimes in the proximal epiphysis of the tibia.


From the structural standpoint, joints may be subdivided into tivo general types —

(fl) Those in ^vhlch a synovial membrane does not develop [synarthroses).

[b) Those with a synovial membrane [diathroses or synovial joints).


The primordium of the skeleton in the membranous stage is essentially continuous. Individual elements first become recognizable when the precartilage of the chondrification centres appears, or when ossification centres start in the membrane bone areas. In either case the residual membrane between these centres eventually develops into the ligaments of the joints. The cells in these areas elongate, multiply rapidly, line up parallel to one another and later give rise to large numbeis of collagenous and some elastic fibres. In a few places such as between the vertebral laminae the fibres are mainly of the elastic type (ligamenta flava). In others, such as the intervertebral Fig. 387 —Lateral aspect of the skeleton of the collagenous fibres are very large and

of a n mm human foetus numerous and are arranged in a definite intcrase on ewis, 1902.) x c 14 weaving pattern In the more central parts of

the ring-like fibrous layers of the discs, the connective tissue cells tend to be arranged in rows, and to become rounded or cuiioidal and finally actually secrete a cartilage matrix about themselves, thus forming Jibro-cartilage.

  • This reminds one of the similar secondary cartilages of the mandible. There is some explanation for the

raembranous nature of the clavicle from the comparative standpoint, as it is believed that the clavicle is, a ^ m part, a modification of one of the membrane bones associated %Mth the opercular apparatus of the gni- Jrc.i S ancestral \ ertebrates



\5 the'C arc the simpler upc of joint thtir development %stU be d«cnb«l first \s has alreadv been staled the bones are first represented bv of the mesenchN-mc uhich later become comerted cither throuijh a cartihginom stage or directh In intrarncm branous ossification into the pnmordia of the future bones Tlic contiguous mesenchMitalous or cartilaginous pnmordia arc connectetl b> means of undifTerentiated mesenchsane If this mc^cncln-mal tissue persists and htcr liecomcs comerted into fibrous tissue as in the sutures betneen the membranous bones of the vault of the skull the iKines are united In fibrous joints without a s>-no\ial cavils Tlirse simple svnarthroses arc callctl le union (svai ) bs a band (desmos) If the mescnchjinal tissue lietween the Ixmes liecomes cliondnfied as for example between the first rib and sternum the joint is referred to as a sirchordrosu or cartilaginous joint llic cartilaginous tns»e lictwcen tbc bons elements mas liecomc ossified at pubertv or later so that the lionrs are joined b^ osseous isssvte ic a nroifoni This u-pc of union occurs between the diaph>-sis and the epiphv'sis of bones


These joints are usuallv formed between cartilage bones but tlic cartilaginous portions ol membrane bones ma> participate in tlicm There is no indication of the site of tbc future s>no\ial joint until after tbc differentiation of the cartilaginous models of the future bones Soon after the cartilaginous models arc laid down die mcsench>-mc between the ends of adjacent cartilaginous elements becomes arranged to form a jointdisc (FiggOSV) In the centre ofthc disc the cells are flattened w hilc at the penphcr> thc> arc contmuouswith the perichondrium of the cartilaginous models Tlic grow th of the cartilaginous elements low ards each other compresses the central part of the joint disc and at the same time a cav its appears in the circumferential part The cells m the centre of the disc soon disappear so tint the cartilage elements come vmo contact with each other and for a time there ma> be a direct cartilaginous union This cartilage fusion is very transitory and docs not involve the full area of the articular urface nor do the cells taking part in the fusion difierentiatc into hvalme cartilage cclU Soon the



Fig 389 — Photomicrograph of a section of the developing humero-radial joint in a 145 mm human foetus X c lo

tion extending into the mter<articular area, surfaces of these accessory cartilages. If the the other, as at the sterno-clavicular joint, a m a “double” diarthrodial joint

cells uniting the cartilaginous elements of the primordia of the bones show mucoid liquefaction, so that a distinct joint cavity is formed (for details, see Whilhs, 1940; Haines, 1947; and O’Rahilly, 1951). The mesenchymal tissue surrounding the developing joint and continuous with the perichondrium differentiates to form a sleeve-like membrane which eventually becomes the capsular ligament of the joint, and, through modifications such as local thickenings and changes in relative position, it also gives rise to special ligaments. The cells lining the articular surfaces and capsule form a flattened mesothelium, the synovial membrane, later, probably as the result of joint movement, the mesothelial cells disappear from the articular surfaces.

Some diarthrodial joints develop intraarticular fibro-cartilages as accessory structures projecting into the synovial cavity from the capsule. These take the form of menisci and partial or complete discs. They are formed from portions of the fibrous capsular sleeve and adjacent perichondrium by partial chondrificaAs the synovial cavity forms it extends over the disc is complete from one side of the capsule to synovial cavity forms on each side. This results


While synovial bursae generally, such as subcutaneous bursae, submuscular bursae, subtendinous bursae and tendon sheaths, are m a sense not directly concerned with the skeleton, it may be stated here that they develop in much the same manner as synovial joints by a progressive oedema and splitting of the embryonic fibrous ti'^sue of the region concerned.^

In the account which has been given of the embryonic development of a typical cartilage

(or “replacement”) bone, the first stage has been described as the accumulation of undifferentiated mesenchymal cells in the areas where the cartilaginous ground substance is later deposited. The antecedents of the cells which form such condensations have been investigated by Fell (1939) and by Jacobson and Fell (1941), who have shown, in the development of the mandible of the chick, that the chondrogenic cells giving rise to Meckel’s cartilage originate from a special proliferation centre in the mesenchyme lying immediately beneath the buccal epithelium. The cells of this proliferation centre are “determined” as early as the third day, to form cartilage. In the hmb-buds the cells of the axial blastemal condensation which later become chondnfied

G 500.— Schemes showing congenital skeletal defeL of the hand (based on Streeter, 1930). A%arual gigantism of digits; ^arrest of development of three digits, C~fusion (syndactyly) of medial three fingers, D-ab

to form the cartilaginous models of the radius



McLean, F. G , and Bloom, W (1940) Calcification and ossification. Calcification in normal growing bone Anal Rec , 78, 333-359

Murray, P. D F. (1936) Bones Cambridge Univ Press, London Needham, J (1931) Chemical Embryology Cambridge Univ Press, London

O’Rahilly, R (1951) The early prenatal development of the human knee joint J Anal Land 85 , 166-170

Peacock, A (1951) Observations on the prenatal development of the intervertebral disc m man J. Anal Land , 85 , 260-274

Prader, A (1947a) Die fruhembryonal Entwicklung der menschhchen Zwischenwirbelscheibe Ada Anal, 3 , 68-83

(1947^) Die Entwicklung der Zwischenwirbelscheibe beim menschhchen Keimling Ada Anal, 3 ,

1 15-152

Romer, A S (1946) The early evolution of fishes Qiiarl Rev. Biol , 21, 33-69

Stone, L S (1922) Experiments on the development of the cranial ganglia and the lateral line sense organs m Amblystoma punctatum J Exp ^ool , 35 , 42 1-496.

Whilhs, J (1940) The development of synovial joints J Anal Lonif, 74, 277-283.

CH vrrrR \iv


The muscular tissue or the Ml ssith the exception of the muscles of tlic iro and the Mhlwt nils of the sneat glands (pi^e 3GC) 11 demetl from the mesoderm iV there arc important difTcrcnccs m the oncm and m the hwioqcncsn of toluniai^ (stnpeti or sep

mental) m olunlar) (smooth sisctral or non «.c^ental), and carrftac muscle tt is neccssir^ to describe Uicir development separately


This musculature is mainly derived from the pam^ial mesoderm by way of the sntmcntally arranged somites but as will be described later certain important parts of jt eg that of the limbs tongue and orbit and the segmental musculature avsoriated with the branchial arches* appear to arise mdependentlv of the somites differentiating in iilu m the mescnchvtnc


The segmentation of the paraxial mesoderm » a fundamental feature of the chordates and it appears early in development fbe embryonic somites arc fonned (page 52), from the paraxial mesotlerm and each of them diffetenuates into \ motomr (which gives ongm to muscle) a dermatome (giving ongin to integumenury tissues) and a sclrrotomt (concerned m the develop, ment of the axial skeleton) It is important therefore to have a thorough understanding of the manner of origin and developmental Imtorv of i)ic somites m order to undcntarid the segmental anitomy of the body Mesodermal segmentation is mirrored in the brain and spinal cord and « closelv related to the segmentation of the catlv excretory svstem

In most human embryos there are ^ occipital and 8 cervical and usually 12 thoracic, 5 lumbar 5 sacral and 0 to 10 coccygeal pair5 of somites (Kunitomo, 1918) The commoner variations from these numbers arc the presence of 11 or 13 thoracic 4 or 6 lumbar and 4 or 6 sacral somites As a rule a variation from the normal somite number in one region is iccom panicd by a compensatory variation sn an adjoining region an additional lumbar somite js compensated by the presence of one less sacra! and an additional thoracic by one less lumbar, etc Thus the total number of somatic segments represented in the average ii mm human embryo (the time of maximum number) is 42 to 44 (fit, 391) The first occipital (Arcy, 1938) and the last seven or eight coccygeal somites undergo nrh retrogression ind seem to disappear enlttely giving n e to no permincni skeletal structures Hie first somite to appear is the first occipital and the succeeding ones conimue to be formed in in uninterrupted cramo-caudal senes (page 52} and difTeremiation also follows this gradient the structures derived from the somites being first produced antenorly However the difTcrential gradient is not so much m favour of the cranial somites as might be expected as it has been shown that the later somites arc pro restively more advanced at the umr of their formation than are the cranial ones (Butcher, 1929) Finally u mav be said that the eirly dificrcntiation of each somite into a dermatome myotome and sclerotome is csventiatly the same throughout the persisting segments (that is second occipital to third or fourth coccygeal) but that the later history of the mjotomic derivatives vanes greatly in dinercnl legjom Somite dilfereniiauon is most typical in the mid thoracic region and therefore, this region wdl be considered first The oncm of the segmental musculature is summarized m Table II

• Thij branchial muscutaiare u probably visceral visceral origin explains why the branchio-mntor nerves ai

i^ngin although its fibres become sinaied Tbjj referred to as ipccial visceral effmtit (p ijS)




In a human embryo of about 5 mm the cells of the ventro-medial portion of, for example, the fifth thoracic somite lose their epithehal-hke character and become mesenchymal (Fig. 369). They migrate medially towards the notochord and soon extend between it and the neural tube dorsally and the aorta ventrally to fuse with similar tissue from the opposite somite (Fig 223). This secondarily mesenchymal portion of each somite is the sclerotome which, through fusion with that of the opposite side, forms part of the pnmordium of an intervertebral disc and the major part of the vertebra immediately caudal to the disc (Chapter XIII). The remaining dorso-lateral epithelially-arranged portion of the somite is the dermo-myotome, from the dorsal





Orbital (extrinsic eye muscles)

3 Hypothetical anterior head myotomes (Direct evidence in the shark )

Cranial III, IV and VI


3 Occipital (Direct evidence disputed )

Cranial XII

Intrinsic of back (extensors of vertebral column)

Dorsal divisions of Cervical i to Sacral 3 or 4

Cervical i to Sacral 3 or 4


Prevertebrals '


Geniohyoid and infrahyoid

Ventro-lateral divisions of Cervical i to 8 Prevertebral portion

Mam lateral sheet

Ventral edge or rectus column

Cervical i to 8


Ventro-lateral divisions of Cervical 3 to 5

Cervical 3 to 5

Anterior and lateral thoracic and abdominal wall

Intercostals, obliqui and transversus

Rectus abdominis

Ventro-lateral divisions of Thoracic i to Lumbar i

Mam lateral sheet.

Ventral edge (rectus column)

Thoracic i to Lumbar i

Posterior abdominal wall (quadratus lumborum)

Ventro-lateral divisions of Lumbar i to 5

Lumbar i to 5

Pelvic diaphragm (coccygeus and levator am)

Ventro-lateral divisions of Sacral 2 to Coccygeal I (Direct evidence questionable )

Sacral 2 to Coccygeal i

Anal sphincter and external genital

Probably same as pelvic diaphragm, but has been traced back only to cloacal sphincter said to be a “skin” muscle

Sacral 2 to Coccygeal i

Upper limb and shoulder girdle

Mesenchyme of limb-bud in man, but phylogenetically from Cervical 3 to Thoracic i

Cervical 3 to Thoracic i

Lower limb and pelvic girdle

Mesenchyme of limb-bud in man, but phylogenetically from Lumbar 2 to Sacral 3

Lumbar 2 to Sacral 3

and ventral edges of which cells proliferate to form a mass lying against its medial or deep surface and separating it from the sclerotomic tissue (Fig 370). The cells of this mass are embr^'onic muscle cells or myoblasts and the mass as a whole is called a myotome (Fig 27-^, Uj The less proliferative lateral portion of the original dermo-myotome is now called the dermatome. As soon as the myotome becomes well differentiated the dermatome rapidly loses its epithchoi character and probably becomes, like the sclerotome, a secondary mass of mesenchyme 11s spreads beneath the overlying ectoderm, clinging to it, so that there is little doulit that i^^is destined to become the dermis and subcutaneous tissue (Chapter XV). In p^t, however, the function of the dermatome is to act as a germinative zone for the myotome (Glucksmann, ' 934 )



The crlls or the ra)otome u.uillt elongate in a p.ttnUel to the Ion; a-tn of the emhoo rhet Itceomc relatnch thtcl. tpmdle, tpherteal nuota and cttopbtnt Net, carlt (Strait and Wctidell toio) these mtohlaiu detelop the poner to Sntract upon st.muhuon althou;!, tt .. unltVeK tint under normal thm are st.muhled unttl serertl t-eehs liter tWindle tnin) Tlte further d.lTerentiat.on of tmobla-ti

mto mu'clc fibres is described on 3*^7 , n i .1 the diiappeirancc of the dermatome the miotome enllr;ra rapidh bo h dorsall) nanlan; the neural tube and lentnlh nhrre It extends into the lomalopleilre At the fibres of the oth thoracic nrrxe prmsini; out fiom the neural tulie rnafe contact oittt tne

m^oiomic cells Tins connexion once established is a peirmncnt one (Chapter \II) Between the fifth and sixth wceh (7-8 mm) the mjotome liecomcs disidcd h) a slight lonttitudmal constriction into a dorsal portion {ffimert) and a \cmro-lalcral portion [hti^mere) (Iiij 392) The nerve likewise becomes split into a dorsal or postenor pnmary ranttu and a ventral or nn/mor primary ramiis connected to the corrcspondint» portions of the mvotome Processes of sclerotomic tissue extend laterall> between the fifth thoracic mjotomc and the fourth (alwve) and sixth (below) m the plane of the rtoovc divadini; the epimcres and hvpomcrcs Tliesc processes wall become the transverse processes of the fifth and sixth thoracic vertebrae As the epimercs and h>pomeres become more complctcl) separated the mcscnch>-me left between them forms a sheet or intermuscular septum which is attached craniall> and caudall> to the two transverse



processes and separates permanently the dorsal division of the muscle from the ventro-lateral division (Fig. 392). This is the rudiment of the lumbar fascia of this segment. Thus the division of the myotomes into dorsal and ventro-lateral portions apparently determines three things . (i) the primary branching of the spinal nerves; (2) the plane of formation of the transverse processes of the vertebrae; and (3) the first intermuscular septum of the fascia of the body, the lumbar fascia Soon after the appearance of the transverse processes the rib elements are laid down in sclerotomic tissue which migrates into the ventral portions of the original intersomitic clefts. As the ribs reach their maximum development in the thoracic region the original segmentation of the hypomeres is retained more obviously in this region. The dorsal divisions

Fig 392 — A schematic representation of the developing musculature in a 10 mni human embryo; somatic musculature, red, branchial musculature in other colours The presumed migration of the somite musculature is indicated by interrupted lines. X c 21.

of the myotomes (epimeres) divide further into a medial and lateral group which will together give rise eventually to the extensors of the vertebral column The medial group, by the fusion of the relatively fe%v consecutive segments and subsequent longitudinal and tangentia sp itting, gives rise mainly to short oblique muscles {semispinalis, multifidus and rotatores) and to the all of which are supplied by the medial branches of the posterior primar>' rami o spinal nerves. The lateral group, by the fusion of a larger number of segments an subsequent splitting, gives nse to the longer muscles (the iho-cosialis, longisstmus a splemus) ivhich are supplied by the lateral branches of the posterior primary rami ( igs. 3J and 394.).



The \ entro lateral divisions (hypomerts) of all the thoracic and the first lumbar mj otomes extend into the somatopleure and gi\e nse to the ventral and lateral trunk muscles i e the flexors of the \ ertebral column These muscles are supplied bj the anterior pnmary rami of the spinal nerves In the thoracic region where the nbs are full^ developed the ^ musculature largely retains its segmental arrangement as the intercostal muscles but IS spht tangentially into three layers (Fig 393) ® superficial external intercostal an inter mediate internal intercostal and a deep intra costal or transversus thoracis muscle In the abdominal region owing to the absence of nbs the vcntro lateral musculature fuses to form a contmuous muscle sheet This nou 393 -A schemsuc .ceuon through the ^orucic

, rcgioa of a 15 mm human emboo 1° show the

becomes suodivideQ into a narrow ventral arran^tnmt of the muscle sheets and the diitnbu

portion {rectus abdominis) which retains some nonoftbespinalnerves to them (after Br>cc 1923)

of its segmental character m the tendinous

mtersecuons and a broad lateral portion which subsequently becomes split tangentially into three layers the external oblique the internal oblique and the transtersus abdominis In the upper thoracic region the rectus sheet normally disappears but is occasionally represented bv the stemahs muscle

Attention must be drawn here to the experimental investigations of Rawics and Strauss (1948) which indicate that in the chick it is only the dorsal part of the trunk musculature that IS denved from the somites According to their observations the ventral trunk musculature arises directly from the lateral plate mesoderm


Only the first lumbar myotome develops in the same manner as the thoracic m\ otomes

Its ventro lateral portion giving nse to the most caudal portion of the fraiurmf and oblique muscles of the abdominal vvall The remainder of the lumbar my otomes have very small ventrolateral portions which give nse mainly to the quadratus iumborvm (Fig 394) The dorsal divisions give nse to all the lumbar extensor musculature the mam portions of which in this region are the sacro spinalis the multifidus and the roiatores

In the more caudal sacral and m all the coccygeal segments the extensor musculature shows earh degeneratn e or retrogressiv e changes and IS represented m the adult by the dorsal sacral ligaments Apparently the ventrolateral dmsions of the third sacral to the first coccygeal segments


persist to form the muscles of the pelvic diaphragm {levator am and coccygeus). Probably the voluntary anal sphincters and the voluntary muscles of the external genitalia are formed from these same segments, although these muscles have not been traced back further than the cloacal sphincter which is said by Popowsky (1899) to be a “skin” muscle (Figs. 397 and 398). At least the medial part of the levator am is considered homologous with the rectus column. On the basis of their comparative anatomy and adult innervation,* it seems justifiable to assume that the muscles of the pelvic diaphragm and the striated musculature of the anus and genital organs are of myotomic origin






The dorsal divisions of the cervical myotomes give origin to the extensor musculature of the back of the neck. This is more elaborately developed than the corresponding musculature of the thorax. The ventro-lateral portion of the myotome in the neck is highly atypical due to the development of the pectoral girdle and limbs, to the recession of the coelomic cavity from the neck and also to the presence of visceral arch structures and muscles. The important

muscles derived from these ventro-lateral portions of the myotomes are the scalenes and prevertebrals {longus capitis and cervicis), which correspond to the intercostal and ventrolateral abdominal muscles, and _ _ the geniohyoid and infrahyoid

1 DORSAL LIMB muscles which correspond to

V-Hl r<NF>nDLE MUSCLES abdomiuis (Fig.

395 ) \ 1 the head myotomes

The only head myotomes

EXTENSOR which can be recognized in , muscles of limb mammalian embryos

_ ^ • are four in the occipital region

I'm 395 — A schematic section through the cervical region of a ('■p'ltr onr'l Of these the first

15 mm human embryo to show the arrangement of the muscle ,

rudiments in the neck and upper limb (after Bryce, 1923) completely disappears, prOD ably by dedifferentiation, ^ at

about the 20-somite stage (Arey, 1938). The other three differentiate into fairly typical sclerotomes, dermatomes and myotomes.

On the basis of comparative anatomy (Edgeworth, 1935) and adult innervation it seems fairly certain that the ventro-lateral divisions of these three occipital myotomes give origin to the tongue muscles, both intrinsic and extrinsic (Fig. 392). However, it has been denied by many who have studied the problem that any migration of these myotomes to the floor of the mouth can be observed during human development. Yet since the hypoglossal nerve, the motor nerv’e of the tongue, is formed by the grouping together of the segmental nerve bund es which grew out towards these myotomes, it seems reasonable to accept the myotomic origin of tongue muscles as a working hypothesis in human ontogeny.

A further speciahzation occurs m the development of the extrinsic muscles of tlie eye (orbital muscles) for here typical somites have not been found m any mammalian embryo

  • Tlic inncrL'ation of adult muscles is used as a clue to their embryonic origin This is

fact that embryonic muscle masses receive their motor inners'ation very early in ontogeny, and that, wui / fcLs exceptions, the adult muscles derived from them retain this innervation regardless of how hir during development “The nerve supply to a muscle is the best index to its morphology. u infallible . ” (Bryce, 1923) See also Straus (1946).


395 — ^ schematic section through the cervical region of a 15 mm human embryo to show the arrangement of the muscle rudiments in the neck and upper limb (after Bryce, 1923)


mnervated b> the Illrd IVth and Vlth cranial nerves (Neal, 1918) Since these muscles an

Fig 396 — A schematic representation of the atrangetnent of the muscle groups deri\ ed from various sources The colour scheme is suDiIax to that rf Figs 391 and 39'*

nen. es are cIosel> analogous to the corresponding ones of higher \ ertebrates it ma> be assumed that the orbital musdes of man are derived ph^logeneticall^ from three pairs of anterior (pre otic) head myotomes The orbital muscles of man are first recognizable as a small aggregation of

condensedmesencb>memtheregionoftheembr>onice>eat about the hmb bud stage (Fig 391)



(For a detailed description of the development of the extrinsic ocular muscles, see Gilbert, 1947 ) The tongue muscles, according to most authorities, appear m a similar fashion in the mesenchyme of the developing tongue. In other words, in higher vertebrates the methods of formation of tongue and extrinsic eye muscles have been condensed and abbreviated so that these muscles now appear to differentiate in situ from mesenchyme.


The pharynx of lower vertebrates is characterized by a secondary segmentation {branchiomensrri) caused by the presence in its wall of paired gill slits. In the higher amphibia these openings disappear at metamorphosis ; in reptiles and birds they are present only m the embryonic states and, in mammals, they are represented by internal pouches and external grooves (pharyngeal pouches and branchial grooves. Chapter X) which approach one another but are normally separated by the so-called pharyngeal membrane, so that actual opemngs from the pharynx to the outside do not occur. The pharyngeal wall tissue between these consecutive grooves forms a series of visceral arches, the ist arch separating the ist cleft from the stomatodaeum. Since, in the primitive vertebrates, most of these arches bear functional gills, each arch consists of the following structures • —

(1) An arterial arch (aortic arch) primarily to supply blood to the gills

(2) A skeletal arch to support the pharyngeal wall and gills.

(3) Muscles to move the arch.

(4) A nerve to innervate the muscle and adjacent skin and mucous membrane.

In mammalian embryos these four fundamental elements are still present even though the pharyngeal structures differ greatly from those of embryos of fishes where the gills function in the adult. In human embryos of 7 to 10 mm. condensations of mesoderm are found in the dorsal end of each of the five (or six, see page 178) visceral arches The mesoderm of the condensations is of lateral plate origin. In lower vertebrate types, however, they are connected to some of the head somites. The condensations differentiate into myoblasts, and the voluntary motor portion of a special visceral cranial nerve grows into each of the muscle rudiments The complicated growth, subdivision and migration of each of these muscle masses are summarized diagrammatically in the series of Figs 391, 392 and 396; for convemence the derivatives of the visceral arches, both skeletal and muscular, are given in Table III It mu^t be pointed out that there is considerable uncertainty about some of the items set forth m Tables II and III As in the case of the muscles of the tongue and orbit, it has been difficult to trace the exact embryological origin of many of these branchial (special visceral) muse ^ from the primary rudiments appearing in the arches Controversy exists chiefly m regar to the derivatives of the more caudal arches. This is because these are relatively rudimentary in mammals and their parts are not as clearly differentiated as in the first two arches


The muscles of the upper and lower limbs (including the limb girdles) are segmenta y innervated by the spinal nerves, but in mammals it has not been possible to trace their ongm back to the myotomes In some of the fishes, however, this has been accomplished T ere or^, the facts of comparative anatomy and comparative embryology and the adult innervation mus be cited as justification for the working hypothesis that the limb muscles are of segmenta It has already been explained (page 359) that the musculature of the ventral body be of lateral plate, and not of somite, origin , it is possible that the limb musculature is 1 c' primarily of lateral plate (i.e , somatopleure) origin

The limb musculature can first be identified histologically in human embryos ol o-io as mesenchymal condensations near the base of each limb bud According to some aut these condensations are found round the terminal ends of the spinal nerves which are ex cn into the limb-bud at this time (Fig. 332). Since muscles will develop m limbs devoi



innervation in certain types of monsters and in experimental animals (Hamburger, 1939) it IS unhkeK that the nerves are concerned with oi^nizint, pnmap^ muscle location

The early limb buds are somevshat flattened dorso ventrally, with cephalic (preaxial) and caudal (postaxial) borders They have a cramo caudal attachment to the body opposite a number of m>otomes (Figs 105 and 392) The superior limb buds lie opposite the lower SIX cervical and the first and second thoracic segments while the inferior buds are opposite the second to the fifth lumbar and the upper three sacral segments Branches of the nerves supplying these myotomes reach the base of their respective limb bud and as the bud elongates to form a limb they extend mto it m such a manner that the limb muscles of the preaxial border


I uceTal Arch



\rne of Museles


Quadrate cartilage— incus

Meckel s cartilage — malleus anterior ligamcrit of the mat leus spheno-mandibular liga ment (’) central core of body mandiole

Muscles of mastication (temporal tnasseler medial and lateral pterygoids) '

Mylohyoid and antenor belly of digastric

Tensor palati and tensor ty mpani

\ Trigeminal mandibular division — (Post tremawc)



Styloid process

Stylohyoid ligament

Lesser cornu and upper part of the body of the hyoid bone

Facial group (including buccinator extrinsic and intrinsic auricular muscles occipito frontalis and platysma)

Posterior belly of digastric and stylohyoid


VII Faual (Post trematic)




Greater cornu and lower pan ot ' the body of the hyoid bone


Probably part of upper pharyngeal muscles I

1 \ Glossopharyn geal (Post trematic)

4 3 and 6

Thyroid cartilage ’Other laryngeal cartilages

Pharyngeal and laryngeal muscles

\ Vagus (superior laryngeal and pharyngeal bran ches) [possibly XI)

Laryngeal muscles

\I Cranial fibres (possibly X) by way of the superior and recurrent laryngeal nerves

’ post 6ih

’Tracheal cartilages

^ Slemomastoid and trapezius

\I (Spinal fibres)

of the upper limb are innervated by the lower five cervical nerves while the muscles of the post axial side receive the last cervical and first thoracic fibres In the lower limb the preaxial group of muscles receives fibres from the second to the fifth lumbar and the first sacral nerves the postaxial group from the first second and third sacral nerves Both pre and post axial muscles lend 10 be split into a ventral or limb flexor group and a dorsal or limb extensor group The nerves of the limbs are likewise divided into anterior and posterior branches supplying flexors and extensors respectively Thus the radval wexxe deivNwi from the posterior divisions of the trunks of the brachial plexus supplies mucics which with one exception are extensors Likewise the ulnar and median nerves which are derived from the anterior divisions of the trunks ot the brachial plexus supply flexor musdes

Modification of the prim, me segmental arrangement of the nenes entenng the limb buds has resulted m the formation of compbcaled plexuses due to caudal migration of the attachment



of the hmb-bud and intrinsic migration of its individual muscles during development. Nevertheless, it is possible to demonstrate that the muscles in the adult limb have a fairly consistent segmental innervation. This is clearer in the upper limb than in the lower where apparently

more extensive migration and rearrangement of muscle has occurred.



tut I ncur



t I


V u











Tig 397 Schemes of the development of the perineal muscles and their nerves of suppl) in the undifferentiated stage and in the male (after Popowsky, 1899) A undifferentiated stage, 2 months B 3 months C — ^ months D —

5 months.


In somite embryos a transverse septum is formed by the caudal portion of the pericardium and the cephalic wall of the yolk sac (Fig. 84) It consists chiefly of the loose mesenchyme surrounding the terminal parts of two pairs of extra-embryonic veins, vitelline and umbilical, entering the caudal end of the heart. At the time of its formation the dorsolateral parts of this septum he opposite the third, fourth and fifth cervical somites (Figs. 217 and 219). In the early hmb-bud stage the myotomes of this region have split into dorsal and ventro-lateral portions and groups of myoblasts from the latter migrate into the cranial surface of the septum carrying their nerve fibres with them. They spread out over this cranial area at the time when the liver bud is occupying the bulk of the septal tissue. The coelomic cavity rapidly extends into the septal tissue lateral, dorsal and anterior to the liver separating from the septum a bulky hepatic mass with its ligaments and mesenteries and leaving a thin cephalic sheet containing the muscle tissue derived from the cervical myotomes Thus a muscular diaphragm is formed. During this time the heart has receded from the neck to the thorax, apparently pushing the diaphragmatic musculature caudally. Although the diaphragm is finally situated in the lower thoracic and upper lumbar region it still retains its motor and, m part, its sensory innervation (phrenic nerve) from the third, fourth and fifth cervical nerves which is clear evidence of its cervical origin. The lower six thoracic nerves supply sensory fibres to the periphery of the diaphragm The final closure of the pleuroperitoneal canals by the diaphragm is discussed un er Coelom in Chaptei X.


The body wall (somatopleure) of eaily vertebrate embryos is extremely thin and transparent,

consisting of a layer of ectoderm and a layer 0 _ _ . , T’V.ic body v'all

parietal mesoderm (Fig. 50) This body va begins to thicken dorsally soon after the myotome form and the ventral edge of this thickening can be seen to advance over the sides of the viscer (Fig 207) until in the human embryo of 20 mm only a broad diamond-shaped transparen area remains round the attachment of the umbilical cord. The transition between the transparent and the thick body w'all is abrupt; the thick portion in the earlier stages contains t



advancmij \entro lateral portions of the in>otomcs and dermatomes In later embr> os these mvotomes difTerenliale to form the mass of body wall muscle the ventral edge of which forms the ventral ribbon musculature of the rectus column Only as the right and left edges of tfus true body wall meet and fuse are the edges of the rectus muscles brought close together This fusion of the body wall occurs first m the upper thoraac region and then suprapubically, and from these two ends approaches the umbilicus Complete replacement of the somatopleure by the true body wall occurs at about the end of the twelfth wceli. of mtra uterine life (70 mm ) In the thoracic region the ribs and right and left sternal bars of cartilage form in the growing body wall The sternal bars are first brought together in the region of the manubrium and gradually fuse tow ird the -viphoid end Failure of the final fusion of these sternal bars results m cleft or forked sternum which is fairly common More gross failure of union of the right and left thoracic wall results m ectocardia or cardiac hernia Failure of umon in the umbilical region results in greater or lesser degrees of umbilical hernia Incomplete closure near the pubis may produce herniation and incomplete closure of the bladder Incomplete development of the infra umbilical part of the antenor abdominal wall associated with incomplete development of the antenor wall ol the bladder results in ectopia vesicae and defects of the external gemtalia (Chapter \I) The line of normal fusion of nght and left true body wall in the abdominal region is the hnea alba

It should be realized that the somaiopleunc body wall contains neither muscles vessels nerves nor skeletal elements These all grow out with the myotomic muscles Even the ectoderm of the somatopleure is not true skin as it is merely a single layer of epithelium The dermis and stratified epidermis, skm glands and hair follicles only develop over the muscular wall although normally the true skin does advance a few milli metres beyond the muscles on to the umbilical cord after the wall is completed


All smooth and cardiac muscle arises mde 398— Schemw of the development of

pendentl, of seg^mal structures (somttes and pTiT.kf

Visceral arches) Most of it is derived from »^9l A — 4-5 months R — 6 months

visceral (splanchnoplcuric) mesoderni that is

the mesenchyme covering the yolk sac allantois (bodv stalk) gut and Us denwUves This includes the longitudinal and circular muscle and the muscularts mucosae of the intestine and the muscle of the trucAci and JronrAi As the embryonic heart aortae 'itellme and allantoic vessels also develop in this mesoderm their muscular coats are also of visceral mesoderm ongin Later hovvever vessels form in the somaiopleunc mesenchyme of the body wall limb buds and head and although their endothelium may be formed by sprouting from the original vessels (page It appears certain that their musculature is fornied from the surrounding mesenchyme Hcn?c it may be said that mesenchyme cv cry-w here is a potential source of the smooth musculature of blood v«sels Similarly smooth muscle of the embryonic and adult urogenital tract must m many places be derived from non splanchnopleunc mesoderm for example the smooth muscle of the vasa deferentia, uterus and ureters

SDCcfiV^ » ““'der separatd, Ac development of the smooth musculature of

nvrcfcl, ® r ® " -'/olops t» Jita from the mesenchi-me sutroundmt; the parenchi-ma of the organ Attention is drawn elsewhere to variations in particular organs


and regions. It must finally be noted that a number of investigators claim that the smooth muscle of the iris is of ectodermal origin (Retzius, 1893; Nussbaum, 1901; Lewis, 1903; Haggqvist, 1931). Such an origin is also generally accepted for the so-called “myo-epithelial” cells of the ducts of the sweat glands. As contractility is characteristic of living protoplasm it IS not surprising that cells other than mesoderm may develop specialized contractile elements. Further, rigid adherence to the germ-layer theory has been rendered unnecessary by modern embryological analysis (page 124). Vinnikov (1938), on the basis of tissue culture studies, has suggested that the iridial muscles are myoneural elements, not true smooth muscle cells. This explanation is not readily acceptable, however, in those vertebrates (birds and reptiles) where the sphincter and dilator pupillae muscles are striated. Whatever the real nature of the muscles of the iris may be there is little doubt that they differentiate from the ectoderm of the optic cup; it is quite otherwise with the ciliary muscle which arises from the mesoderm surrounding the cup.


Smooth Muscle. Nearly all smooth muscle arises from mesenchyme, but there is a fundamental difference of opinion on the nature of mesenchyme which complicates any description of its histogenesis. Many investigators regard the mesenchyme as being essentially a syncytium m which the processes of adjacent mesenchymal cells are fused to form a protoplasmic continuum, while other workers (notably Lewis, 1922) maintain that while there is contiguity of the processes, there is no protoplasmic continuity If there is no primary syncytial arrangement the transition from a mesenchymal cell to an embryonic smooth muscle cell is easily followed as far as the microscopically observable changes are concerned. The myoblastic cells and their nuclei elongate, becoming fusiform, and arrange themselves in groups and layers which are orientated in the same direction In cells in the transitional stage rows of cytoplasmic granules are seen which coalesce to form myofibnllae. These may be artefacts as they have not been demonstrated in living smooth muscle cells which appear to possess a homogeneous cytoplasm. Later both coarse collagenous and fine reticular intercellular fibrils develop throughout the smooth muscle condensation. These connective tissue fibrils bind the smooth muscle cells into functional groups. Some embryologists regard these fibrils as products of myoblasts, but It is probable that they are produced by a fibroblastic differentiation of some of the mesenchymal cells in the original condensation If the former interpretation is correct it indicates a close relationship of smooth muscle cells to certain types of connective tissue cells.

The origin of smooth muscle cells from a mesenchymatous syncytium has been descnw by a number of workers including McGill (1907) and, more recently, Haggqvist (igsOthis view the assumed connexions between the processes of adjacent primitive mesenchyma cells in an area where smooth muscle is to be formed become progressively broader uim eventually the myoblastic mass presents the appearance of a multinucleate synctium. In t is syncytium there are no clear indications of cell walls and the myofibnllae which develop appear to pass through long stretches of cytoplasm and past many nuclei without interruption.

It is generally agreed that growth of smooth muscle can take place by the differentiation of myoblasts from mesenchyme until quite late in development, or by mitotic division of already differentiated smooth muscle cells or by the increase in size (hypertrophy) of individual cel s All of the changes have been described as occurring m the pregnant uterus, but the re importance of each in the growth of this organ in pregnancy has not yet been finally assesse In general in adult smooth muscle some power of mitotic activity is retained, but the capaci for regeneration is small and any extensive injury heals by fibrous tissue replacement (scarringj.

Cardiac Muscle. Although this muscle is involuntary it is cross-striated like muscle; furthermore, it appeals to form a syncytium* and the mesenchymal cells from w

• The s>-ncytial nature of heart muscle is almost universally accepted, but there is some f particularly from tissue culture observations, that the syncytial appearance is more apparent . (.’ndent two cells, apparently united by an extensive cytoplasmic bridge have been observed to contract wiin 1 rhythms (Less is, 1926)



the muscle IS dcs eloped $ho%% a precocious fusion of their processes and extensive mtrac^ toplismic development of fibrib The fihnls of cardiac muscle develop like those of smooth muscle, thev arc first indicated rows of fme c>toplasnuc granules which coalesce to form the fibrils They form m the cytoplasm on all sides of the nuclei and extend uninterruptedly through the intercellular processes from one cell to another They multiply greatly in number, apparenUy by longitudinal splitting as well as by new formation Like the fibnls of voluntary muscle and unlike those of the smooth variety they become segmented bv the formation of allcmatmg light and dark portions The light bands of ncighbounng fibnls come to he opposite to one another the dark bands hkcvnse thus giving the cross smation effect of the muscle fibres Although the fibnls arc clearly seen m fixed cardiac muscle they are not icadilv demonstrated in the living muscle cells (Leviis I96)

A peculiar feature of adult cardiac muscle is the appearance of intercalated discs which at first sight seem to cut transversely across the intercellular processes separating the indmdual cells These are very scarce or absent m foetal hearts and only liecome numerous some years after birth They are not complete sepia across the processes and therefore do not change the syncytial nature of the muscle

The most unusual feature of the heart muscle and one of great practical importance is the conducting system {Putkinje tissue) concerned with the miliaiion and propagation of the cardiac impulse and assuring an efficient and rct3;uUf contraction sequence m the organ These cells are cardiac muscle cells specialized physiologically for conduction rather than contraction They become noticeable m late embryonic or early foetal hearts as bundles of muscle cells with relatively fewer fibnls and relatively larger diameters than the bulk of the cardiac muscle cells (Godlewski 1902 Sanabna 1036) They are mainly located just external to the endo* cardium and extend waihoul interruption from the atnum to the venincle as the aino rentncvlar bundle

Voluntary Muscle Myoblasts destined to form voluntary striated muscle fibres may develop from citlicr somite or non somite (eg branchial or possibly lateral plate) mcscnchyTOe The myoblasts derived from either of these sources are short spindle shaped cells with spheroidal nuclei and a relatively large amount of clear cvloplasm Rous o£ Fine granules soon appear m the cytoplasm and fuse to form fibrils which pass from one end of the cell ^on all sides of the nucleus) to the other (I ig 94) These granules are regarded by some as mitochondria but this seems improbable (Ueed J936) Neiertlieless the mitochondria arringe themselves in close association with the developing fibnls ^^hlch arc at fini homogeneous but later develop cross striations rcgularlv distributed along their length These are the precursors of Henscn s lines in the A discs of adult stn tied muscle Still later other

thickenin'^s vihich become Krauses membranes in the 1 or 7 discs appear midviav bctvicen successive A discs The fibrils attain this segmental structure before they arc numerous enough in an individual cell to produce the appearance of cross stnation and while the cells are still tmi nucleate This is the state in the early foetal stage (third month) The fibnh multiply rapidly by new formation and by longuudmal spUutng and it the same time the mv oblasts become multinucleatcd This may be the result of secondary fusion of separate cells or the multiplication of the nuclei without cytoplasmic division (Weed 1936) or both These processes result in the production of multinucleatcd muscle fibres In the last three months of gestation the previously centrally located nuclei seem to be crowded to the surface of the fibre by the fibnls now densely packed asm the adult condition The muscle spindles (proprioceptors) ofvoluntan muscle can be distinguished at about the twelfth week of gestation vCuajunco 1940) Thev deselop practically in the same manner as the contractile elements but their nuclei remain central and their fibrils are coarser and not so denselv packed Sensory as well as motor nerve endings also become intimitely associated with the muscle spindles

Eanj-smaled musefa gro« b, d.lferoMlion ornE^. mj oblasts from the atijacem mesen chyme b) mitotic dmsions of early myoblasts before fibnls have formed and by the increase msiae of the indmdoal fibres Post natal gnnsth seems to be almost entirely due il etilargemcnt


of pre-existing fibres The regenerative capacity of adult striated muscle is limited and defects are mainly replaced by fibrous tissue (see Gehlen, 1937; Clark, 1946).


Fasciae are made up of fibrous tissues. (For a description of the histogenesis of connective tissues see Chapter VI ) Developmentally fasciae arise from the mesenchyme between, and surrounding, the various organ rudiments; e g , around the primordia of muscles, bones, vessels, viscera The mesenchymal cells may differentiate into one of the following —

(1) Dense fibro-elastic tissue which makes up most of the more definite named fasciae of the body, especially the muscle fasciae (epimysium).

(2) Areolar tissue which is the chief constituent of subcutaneous tissue (“superficial fascia”) and of fascial spaces where movement occurs between condensed fasciae

(3) Reticulum which is an even more delicate fascial material found as the supporting framework of fat masses and of the tissues of most organs,

(4) Adipose tissue

Since most of the anatomically and clinically important fasciae are associated with the primary muscles (1 e , group i) the development of this group only will be discussed Kuhn (1927) has shown that the prevertebral fascia can be traced back to that surrounding each prevertebral and scalene muscle mass; the deep fascia of the back of the neck or nuchal fascia to that mesenchyme separating the dorsal from the ventro-lateral divisions of the myotomes in this area and investing the muscle masses formed from the dorsal portions; the pretracheal (infrahyoid) cervical fascia to the mesenchyme enveloping the rectus column of the neck, and the investing layer of deep cervical fascia (external cervical) to that ongmally surrounding the sterno-mastoid-trapezius sheet The separation of this sheet into the more posterior trapezius and the more anterior sternomastoid muscle leaves the investing layer of deep cervical fascia covering the posterior triangle of the neck The lumbar fascia, as has been indicated earlier (page 358), arises from the mesenchyme separating the dorsal from the ventral division of the myotomes This intermuscular septum exhibits a characteristic of many other fasciae in that it comes to serve as an attachment for muscles, being greatly strengthened and thickened by the formation within it of sheets of collagenous or tendinous fibres. There is considerable reason to believe that the tendinous fibres develop in these fasciae in direct response to mechanical stresses. Such tendinous fasciae are called aponeuroses

Since mesenchymal tissue connects all adjacent fascial rudiments it is obvious that fasciae will become adherent to their neighbours during development. Thus in the neck the caroti sheath, prevertebral, pretracheal, and investing layers of the deep cervical fasciae are all more or less fused with one another. Many of these connexions seem to be due also to development of fibres in response to lines of stress Fasciae developed around a muscle mass in one region are usually continuous with fasciae developed in connection with the. homologous group m t e adj'oimng regions, e g., the nuchal fascia of the back of the neck is continuous with the lumbar fascia, as both are developed around the dorsal divisions of the myotomes.


Arcy, L B (1938) The history of the first somite in human embryos Contnb Embryol , Carnegu Insi

27 , 233-269 • neural

Butcher, E O (1929) The development of the somites in the white rat and the fate of the myotomes,

tube, and gut m the tail Am J Anal, 44 , 381-439 o rn T ondon

Bryce, T. H (1923). Myology /a Quam’s Elements of Anatomy, 4 , pt 2 I^^^Smans, Green is,. V

Clark, ^V. E Le Gros (194^) experimental study of the regeneration of mammalian stripe

Anat Land, 80 , 24-37. , t? h ’ol Carneg»

Cuajunco, F. (1940) Development of the neuro-muscular spindle in human fetuses Contnb. Emory >

Inst HWi , 28 , 97-128 I

Edgewortli, F. H ( 1935 )- The Cranial Muscles of Vertebrates Cambridge Univ Mtch

Gehlen, H. ion (1937)' Ueber die Regeneration der quergestreiften Muskulatur Rowe rc Organ., 135 , 609-619



Gilbert P \\ (1947) The origin and development cS the extrinsic ocular muscles m the domestic cat J

Glucksmann A (1934) ^^Ueber die Entwicklung der quergestrciften Muskulatur und ihrc funktioncHen BezichungenzumSkelettmderOnto und Phylt^eniedef Wirbeltiere ^ ges Anal I Z EntaCtsch

Godlewski E°^(i902) Die Entv,icklung des SVelci und Hen muskelgcviebes dec Saugetiere -treft / miAr Anat u Ent GO xii'-is^

Haggqvist G (1931) Gcivcbe und Systemc der Muskulatur In Ilandb d Mikr Anat d Menschen (v Mollendorff) 2 pt 3 Springer Berlin

Hamburger V (1939) The development and innervation of transplanted limb primordia of chick embryos J Exp 80 347-385

Howell A B (1936) The phylogenetic arrangement of the muscular system Anat Rte 66 295-316 Kuhn J K (1927) Die Enti icklung der Halsiaszien bcim Menschen Morph Jahrb 58 567-604 Kumtomo K (igi8) The devcloptneni and redaction of the tad and of the caudal end of the spinal cord Confrii Embrytl Carnegu Inil Hash 7 i6i-ig8

Lewis l\ H (1903) Wandering pigmented cells aruing from the epithelium of the optic cup with observations on the origin of the M sphincter pupillae in the chick Am J Anal 2 405-416

(igto) The Development of the Muscular System In Manual of Human Embryology (Keibel and

Mall) 1 Lippincott Phda and London — (192a) Is mesenchyme a syncytium’ Anal Ree 23 177-184

(1926} Cultivation of embryonic heart muscle Contrsb Embryol Carnegie Iiul Wash 18 1-21

Mann Ida C (1928) The Development of the Human Eye Cambndge Univ Press London McGill C (1907) The histogenesis of smooth muscle in the alimentary canal and respiratory tract of the pig Inter Monatsehr J Anal u Phys 24 209-245 Neal H \ (1918) The history of the eye muscles J Morph 30 433-453

Nussbaum M (1901) Die Entwicklung der Binnenmuskein des Auges der VVirbeltiere Ueh mikr Anal 58 19^230

Popowsky J (1899) Zur Entwicklungsgeschichie der Dammuskulaturbeim Menschen Anat Ile/le 12 16-48 Rawles Mary E and Strauss \\ L jun (t^8) An experimental analysis of the development of the trunk musculature and the nbs in the chick Anal Ret 100 755 Reiaius G (1893) Zur Kenninu vom Dau der Ins Biol Untersueh \F 5 43-47 Sanabria T (1936) Rccherches sur la diCTerentiation du tissue nodal et cennecteur du coeur des Matnmiferei Arch Bwl 47 1-70

Straus \V L (1946) The concept of nerve muscle specificity Biol Rev 21 75-91

and Weddell G (1940) Natvite of first visible contiactions of fentlimb musculature in rat fetuses

J Jieurephysiol 3 358-369

Tench E M (1936) Development of the anus in the human embryo Am J Anal 56 333-345 Ninnikov J A (1938) Growth and transformation m vitro of myoneural elements (sphincter and dilatator of the tris) Compi Rend {Doklady) Atad Sts (VRSS) 18 119-120 Weed I G (1936) Cytological studies of developing muscle with special reference to mvofibnls miwchondna Golgi material and nuclei ^<im / ^r//A-r v mikr Inat 25 516-540 Windlc \V F {1940) Physiology of the Fetus Saunders Phila and London

Zechel 0 (1924) Uber Muskelknospen beim Menschen ein Beitrag aur Lehre von der Differenaicrune des Myotoms / ^»i«r 0 Enl 74 593-607 ®



the skin and its derivatives

is d “eloped jp‘° cpMermis and denrns (conura »

he ectoderm covering the surface 'of the emh ^ and the underlying mesenchyme,

of cubo.dal cells. By the 5 nsm. sLe it S'"

o. and a deeper layer, the epidt JiTpro 'er’ Tb "r* “ !=»■■- "■eV»

^ -mporary protective membrane for the laft ^ i.- former appears to be in the nature y active multiplication the cells of the ?ermina? T regarded as a germinal zone,

gra ually thickens, and, at differing rates in W'ff origin to an intermediate layer M'hich

into typical stratified squamous epithelium parts of the surface of the body, differentiates

original germinal cells, persists as the stratum ol <^eepest layer, corresponding to the

in order, from within outwards • a stratum ^ tvum. Superficial to this there gradually appear cjnnenm By the 200 mm. stage the iel^vZTrT ^ stratum lucidum and a siralmx

IS IS possibly in part due to the eruntinr^^fi^u ^ been desquamated (Fig-SppD).

pitnchium for this transitorv , hairs (see later) whence the alternative name of

/ V pun aue to the erimtinr, l • 7 — uesquamacea trig.

pjMtnchium for this transitory embrvonm * later) whence the alternative name

^baceous secretions and, as develoL^nr covering. To this cast-off layer are addf

most part {stratum disjunctum) of the yet more ectodermal cells from the oute

vermx caseosa. This persists to full term eorneum to form a whiPsh cheesy substance, tl

term covenng over most of the skm but more particulari; ft

— — - fun V ^ the joint creases. The vernix may have

c ion in protecting the underlying epidermis fron maceration by the amniotic fluid.

t an as yet undetermined stage, but probably befon ceH ^tage, the ectodermal epidermis is invaded b)

s o neural crest origin (see page 271). These cells latei eve op extensive processes, for which reason they are


60 mm

<OOll M

'm ih^ to show stages

of the cpidlr

Fig 400 — Photomicrograph of silver impregnated mclanoblast in the epithelium of a 93 mm, human foetus, X c rioo,



37 ‘

frcqucntl) called dindrilic cells and they de\clop a marked afTinitv for siher salts B% the too mm stage these argemafTin dendritic cells ha\e a wide dntnbutinn (Fig 400) m the foetal epidermis (Bo>d 1^9) In the foetuses of negroes thc> gradualK desclop melinm pii»inent Zimmermann and Cornbleet t948) which as in the adult (Rillmgles 1949) the) can transfer to the other ceils of the epidermis Because of this ahilits tosxnthetize melmm the dendritic cells are also called melanoblasts In the foetuses of white races the dcndntic cells of the epidermis do not produce osert melanin but as 1$ well known m post natal life thes possess mclanogenic possers tnd m foetal life similar cells in hair follicles (Fi^ 401; can pigment the growing inir shafts

The dermis the deeper laser of the skin has its origin from the mesench)me undcrl)ing the epidermis and is in part at least densed from the dcrmatomic portions of the somites For this reason each dermatome is sometimes called a eulis plait Some of the cells from each derma tome are bMie\ed to migrate senlnlK where, with reinforcement from the cells of the somatopleuric mcsenchsTTic the) develop into the general dermis of the bod) wall and Umbs \t about the jo mm siige fibnllae appear in the interstices of the dcrmitomic

Fir 401 — } })Oi MTucrograpb of nher impregnsird melanoblut m scalp hair follicle of a 03 nun human foetus y c 460

material and Ot a later period these filtnllae can be disiinautdted as colhgenout and clastic Itbres B) the 6 o mm stage prohrerations of the cortum form papillar) projectionj tnw the ^idermis and the supctricial part of the cniium becomes compact Fat appean in the deeper iwrlion tthich hecotnes the general subeutaneous tissue |subct>niiml Farit in deielopraent mrm na,° " nmmbrane of homogeneous malenal separating the slratum

feerf I r "1 'T ndges ts nell established m

foetal life and finger prints are tndtttdtial before birth (Cummins loan)

There ate marked regional and specific differences in llie carb deiclooment and h.stn genesis of dilTercnt parts of the skin (see Steiner, igzp 1930 for detailsl

lire nails of the f.ngets and toes make their appearance lonards the end of the third month (50-60 mm stage) as thickenings of the enidermw called the primar) nail fields These thickenings ire initialU siluiled near the tips

fingers and migrate arm eU or p:u c to their dorsal aspects This mi^a

“i?" 1 ‘fie supply of

prtraat) nail fields lag behind , I" ■“P'nent so that each comes lo “ *»Po depression bounded

\ WW'j '! nndctcnls P,„

0 liferation of the cells of the natl field in a

•" dnelop ment ol a hair and us related s baceous gtand^



and the outer layers of the stratum corneum, gradually gives origin to the nail. The nails grow slowly in foetal life and do not reach the tips of the digits until the end of the ninth lunar month, reaching the tips of the fingers rather earlier than the tips of the toes.


The first hair of human embryos begins to appear m the third month as solid cylindrical epidermal downgrowths into the underlying dermis , these become club-shaped and the thickened lower part of each downgrowth becomes mvaginated by a small mesodermal papilla (Fig. 402). The central cells of the downgrowth become spindle-shaped and keratinized, fusing together to form the hair shaft. The peripheral cells become cuboidal to form the wall of the hair follicle. Growth of the hair results from continued multiplication of the epidermal cells around the papilla. The first hairs appear m the eyebrow and upper lip regions (see also page 1 1 7) ; towards the end of the third month extensively scattered fine hairs called lanugo appear. These are chiefly shed shortly before or after birth and are replaced by coarser hairs which arise from new follicles.- Dendritic cells appear m the hair roots at about the 100 mm. stage (Fig. 401; Boyd, 1950). In dark-haired individuals melanogenesis is active in the hair follicles during the second half of pregnancy.


Thesebaceous glands arise as epidermal buds from the cuboidal cells of the hair folhcles (Fig. 402) during the fifth month of foetal life. The buds grow into the surrounding mesoderm where theif ends become lobed. The central cells undergo a form of fatty degeneration and pass into the_hair follicle as sebum. A few sebaceous glands develop from the epidermis, independently of hair folhcles, in the anal region, nostrils and eyelids. The tarsal glands are specialized sebaceous glands and develop m a similar manner to them.


The sweat or sudoripurous glands begin to develop at about 100 mm. stage as solid cylindrical epidermal downgrowths which are more compact than those of hair primordia and do not develop mesench^Tnal papillae. In later stages the downgrowths become coiled and soon develop lumina by the breaking down of their central cells They usually retain two layers of cells in their walls, an inner layer limng the lumen (the gland cells) and an outer layer which gives origin to the so-called myoepithelial cells of the glands (page 366). Specialized sweat glands are developed in certain regions, e.g., axilla, external auditory meatus and eyelids.


The first stage in the development of the mammary glands takes the form of a pair of external thickenings, the mammary ridges or lines which extend on each side of the ventral bod)

. / wall from the base of the fore-limb bud to the region medial to the

Fig. 403 — Drawing to show the position of the milk ridges

hind-limb bud. Each mammary line appears at about the 7 stage but is not easily recognized until the 1 1 mm. stage. Its cau a two-thirds normally disappears before the 20 mm. stage, but in t e intermediate portion of its cephalic one-third it thickens to form t e mammary primordium (Fig. 403). The ectoderm of the primor lurn consists of a superficial layer of flattened cells and a deeper layer o cuboidal cells. By about the 40 mm. stage the ectodermal thickening of the future gland has penetrated into the underlying mesenc yme, which has now become condensed (Fig. 4^4) • This primor luro grows slowly into the underlying dermis and gives origin to a lou •sixteen to t\\ enty-four secondary sprouts around which fat is ^

In the eighth and ninth months of intra-uterine life the initia growth and the sprouts become canalized. The secondary outgroiv become the lactiferous ducts and the tertiary sprouts from them or



,ht aUeol. and small ducts of the <;la„d The ongtnal donn^ronlh as an epidermal pit into si hich the licliferous duels open At about full term w hter a non of mesoderm the pit causes its elevuuon aboae the surface of the adjacent sUn to form the mppk If this does not occur the ducts open into pits instead of on nipples defect knoun as m\ cried or crater nipple At full term the rudimentary mammary glands arc similar in both sexes and mas occasionally show 13ns of secretory acti\ity (witch s milk) This activaiy may be due to the production of the hormone prolactin by the pituitary gland of the infant before and after birtli It JS dIno possible that this hormone is of maternal ongm and crosses the placental harrier (sec Smith 194^ for discussion) In the male the glands normalK remain rudimcntan throughout life though thes may rarely become enlarged (gymaecomasiia;

In the female at pubcrt\ and during and after pregnancy they undergo marked changes which invohe a high degree of hormonal co ordination between the glands the pituitary and the oaanes

As occasional anomalies additional nipples polythelia can be found at any point along the milk line (Fig 403) Extra mammars glands polymastia or absence of the mammarx gland amastia) are much rarer


Teeth are restricted to tlie jawed (gnaiho stomatous) \crtebnics They ha\e no homo logues in the mxertebrates lower chordales or cvclostomes They can be regarded as nets acquisitions for seizing holding and masticntmt, food Teeth are fundamentally dent atnes of the derma! skeleton being basically similar to the placoid scales of the Euselachn

Each tooth has a basis of dentine which is ~

of mescnchymatous origin and IS covered by 'C”

enamel which is Ibrmed by specialized ecto " c* ^ 'i

dermal cells In the course of vertebrate rvolu tion the teeth have undergone many modihca tions In the Eusclachu all the teeth arc similar m form and have no firm attachment to the jaws ^Vhcn such a tooth is lost in front another one moves forward to take its place Man and most other mammals have two sets of teeth a tem porary set or milk dentition and a permanent dentition The mammals are therefore classed as diphyodonl in contrast to the other vertebrates,

"Hh indcfimte succession of teclh such smehrates ate poljphjodont In mammals the teeth

arehxedhrml) m the jaws and have undergone difTercntiation amongst themselves The homo

dom condition of the more pnmuiv e v ertebrates is replaced by a heterodont condition m w hich teeth are differentiated as incisors canines premolars and molars m the permanent dentition

Fig 404 — \ Fhoiomicrograph of a section of the developing mammary rudiment m a 44 mm female human embryo x c 115 B Photomicrograph ofa section of the developing mammary rudiment in a 160 mm female human foetus c 75 C Photomicrograph of a section of the developing mammary rudiment m a mm male human foetus X c 7^








The first indication of the development of the teeth is the appearance during the 6th iveek (embryos of 1 1 mm.) of a curved continuous ectodermal thickening, the dental lamina, on the oral surface of each ja-w. The dental lamina (Fig. 405) consists of a surface layer of flattened

cells lesting on a basal layer of taller cells, which have many mitotic figures. The basal epithelial cells are separated from the mesenchyme by a basement membrane. Each lamina soon lies within the concavity of the second ectodermal thickening, the lip furrow band or labio-gmgtval lamina (Fig. 405). By the 27 mm. stage the epithelium of each dental lamina shows on each side in each jaw five symmetrically arranged budhke round, or oval, swellings which are the primordia of the enamel organs of the deciduous teeth (Fig. 405). As the ectodermal tooth bud continues to grow, it sinks fin ther into the mesenchyme, where it forms a small indented sac, the enamel organ, joined to the dental lamina by a constricted neck. At this stage the enamel organ consists on its indented, and deeper, aspect of a layer of columnar cells (inner enamel organ epithelium) which are continuous with more cuboidal cells (outer enamel organ epithelium) around the convexity of the organ. The cavity of the enamel organ contains a central core of ectodermal cells betw'een which intercellular fluid accumulates, so as to form a stellate reticulum (Fig. 406) . The intercellulai fluid is of a mucoid nature rich in albumen. Although the stellate reticulum is of ectodermal origin it is morphologically very similar to the gelatinous mesenchyme, or Wharton’s jelly, of the umbilical cor In subsequent development the indented layer of columnar cells will give oiigin to the enarae and is therefore called the ameloblastic layer Un er the orgamzing influence of the ameloblastic layer, the mesenchyme in relation with it prolifera^ and condenses to form the primordium o t e dental papilla (Fig. 407). The ameloblastic la>er is progressively mvaginated by this dental ^ and the cells of the latter in contact ivit ameloblasts become arranged into a odontoblastic layer (Figs. 408 and 409). T is ay gives origin to the dentine. The remaining ce of the mesodermal papilla differentiate into “pulp” of the tooth. The outer enamel ep thelium at the end of this stage folds between %vhich capillary vessels deve °P ^ mesenchyme. These capillanes supp y nu to the avascular enamel organ but the outer enamel epithefium is never penetrated by me ^ During the time that the tooth is developing to this stage, impoitant changes are =

in the lip furrow band. The deep cells proliferate and invade the underlying mesencn>






Fig 4^5 Sagittal sections tHrough the hp and anterior part of the mouth showing schematicallv stages in the de\elopment of an incisor

tooth A — 20 mm embryo B :

br\'0 C — 55 rnm, embryo

J7 mm em



and the band soon hollows out to become the hp sulcus between the developing lips and cheek and the gums (Figs 405 and 407) The ameloblasts Ia> dossn succeeding of calco

piobulm which later harden to form the enamel rods which arc deposited on the outer surface {Fig 408) of the dentine which is being laid down b\ the odontoblasts, enamel and derUine production thus proceeds simultaneousK Growth of the tooth takes place from the den tine enamel junction w here the oldest dentine and enamel arc in apposi non In both cases the acti\ e secrc tor> cells recede as the dentine and enamel matrices arc laid down The ameloblasts final!) disappear leaving on the surface of the enamel a thin covering (Nasmvths mem brane or dental cuticle) The odonto blasts do not disappear but persist as a regularly arrani^ed cellular lamina beneath the last formed dentine and separating it from the mesodermal papilla which has become richly V asculanzed to form the dental pulp The calcification of the tooth which begins during the sixth month of foetal life results in the formation bv — Phototmerogrsph ofa srtiion ofa developing lo\ er

full term of a well developed crown looihm a so mm human embryo x c 45

The root of the tooth is not formed

until shortly before eruption, and it becomes intimately related to the developing mandible or maxilla and attached to the bone bv specialized cement tissue which together with* the periodontal membrane is derived from the mesodermal follicular sheath The dental lamina extends backwards beyond the last deciduous tooth germ and slowlv forms the enamel organs of the permanent molars which have no deciduous pre cursors At about the 50 mm stage the dental lamina related to each deciduous tooth produces secondanly solid epithelial buds on its Imgual side (Figs 405 407 and 409) These are the enamel organs for the perma nent teeth The dental lamina persists as an epithelial tract the

gubernaculum denlts which for sometime attaches the apex of the deciduous and permanent tooth to the opitholtum of iho gum K late disappears completel) Some calcification occurs in the permanent teeth before birth For detaik see Orban (1944)

Teeth seem to be latgelj self dinerentiatiirg and Glassione ( 1 936) has groii n rat tooth germs m wtro and her Kpertmems shots that sshole or tooth germs possess remarkable ponets of htstologtcal differentiation in tissue culture The presence of the internal enamel epithelium IS apparently essential for odontoblast foiTnation and one of the functions of the enamel organ














u 409 — Photomicrograph of a section of a developing lower tooth in a 180 mm numan foetus X c 28 Note bone of mandible, and inferior dental nerve

Fig 408 • — Sagittal i.ccrion through a developing incisor tooth " lowmg schematically its constituent port' in a 220 mm human embryo.

IS to determine tne gross morphological structure of the tooth (Hahn, 1941).

During the period that the teeth are developing and growing an adequate supply of calcium and phosphates is required ; in addition, vitamins A and D are essential for their proper formation. It has been shown that the diet the mother during pregnancy has a profound influence on the subsequent condition of the teet of the child (Mellanby and Goumoulos, 1946) The salts of calcium and phosphorus are essentia

for the formation of both enamel ^hd dentine, while vitamin D is required for the utilization 0 these salts. When vitamin D is ^^eficient during the development of the teeth after their eruption the surfaces of the teeth are rough instead of smooth and shiny. If there is a deficiency of vitamin A, the ameloblasts fail to differentiate properly, and as a consequence their organizing influence upon adjacent dentine is disturbed, and so dentine is formed in an atypical manner. There IS a close relationship between the structure of a tooth and its liability to caries (King, I 94 ®r


Beielander, G (1941) The development and structure of the fiber system of dentin Anat Rec , 81 , 79 9 ? T>* , \ Dendritic cells in pigmented human skin J Anat, Land, 83 , iog-115

^ , D949) -^gentophil cells in foetal ectodermal epitheha 7 Anat, Land, 83 , 74

M hair follicles J Anat , Land , M, 62 human

’k (*9^9) The topographic history of the volar pads (walking pads, Tastballen) in

Wnhn w’p development of tooth germs in vitro J Anat, Land, 70 , 260 266 igf,tcd.

-The capacity of developing tooth germ elements for self differentiation when P

J Dent Res, 20 , 5-20 i- 6 6 , j-n

Mplfpnh, ° Cental Disease Committee, Med Res Cncl Sp Rep , Ser No 21 b H M S O , Lond

Mellanb>^May and Coumoulos, Helen (1946) Teeth of 5-year-old London school-children BMJ,

Embryology Kimpton, London

St#-inpr K ('innn\ Physiology of the Newborn Infant Thomas, Illinois xj , , Uber clic

’ I 9 9)' nr die Entwicklung und Differinzierungsweise der menschlichen Hau

der menschlichen Haut Zel(fr’sch , 8 , 691-72°^^ , d« 

(L93o) 11 . Die embryonale Entwicklung der Haut^biete mit fruzeitiger Mehrschicht g

Epithels Z An^ EntwGesch., 93 , 1 50-1 73 _ the Ncgrn

Zimmermann, A A , and Cornbleet, T. (1948). The development of epidermal pigmentation m fetus J Iniest Derm ,ll 383-395



ConsidiTtd objKtnely and samt^aU} the embr^olog} of man has

no more interest than that of any other mammal or lerttbrale and from this standpoint special tndeaiours to noth out human embrjologj by t*self may to be misplaced — Keibet {iQio )


The study of human dcNcIopment has been greatly influenced by the knosvlcdt^e obtained as the result of imestigations on other vertebrate types This has been in part due to the greater ease with which closely sta ed embryos of kno^n age can be obtained m animals and to tlic absence of limitation of expenmcnl Further, in order to explain certain peculiar structural and functional phenomena occurring tn human development a knowledge of comparauve embryology is imperative Thus the presence of the notochord, the visceral arches, the sequence of kidnevs, the functional differentiation of the nervous system and the foetal metabolism can best be understood on the assumption that they arc at least in part features inherited from ancestral stages in the development of the human race Since many ancestral organs seem to have disappeared entirely, it may be assumed that during the course of evolution features have persisted when they are functionally necessary during development as for example the mammalian mesonephiw or when they provide a scaffolding for some essential structure of the later embrvo or adult, as for example, Meckel s cartilage

Fifty years ago most competent zoologists vvere satisfied to explain embryonic development mainly in the terms of the so called Law of Reeapitulalton or Law of Biogenesu This law stated that embryonic development repeats m order the adult stages through which the race has passed during its evolution This is often expressed by the statement Ontogeny repeats phylogenv While there is nothing in the known facts of embryology evolution or genetics to show that ancestral adult features arc handed down by heredity to the embryos of more advanced forms yet there arc a multitude of characters appearing temporarily during the development of an individual that arc known to be primitive and can be explained only in the light of the evolutionaiy past of the speaes Most modem embryologists therefore, would restate the Law of Recapitulation in the highly modified form that Ontogeny repeats funda mental steps in the ontogenies of ancestral forms especially when these steps are of structural or functional importance to the indindual (de Beer 1940)

Although the original law especially as expressed by Haeckel (1874), has been replaced by a more tenable modem version the general idea of recapitulation has been of the utmost importance m the stimulation and imerpretation of investigations in the field of comparative embryology For one fact which does not seem tofit in with the modern thcorvof recapitulation a thousand can be cited which arc meaningless without it No matter how inadequate the modern theory may be regarded as an explanation of the reason for the developmental course taken by a species the general pnncjple wiH always be found of value in embryological study With few exceptions, the younger the stage of development of an embryo of a particular species the lower is the animal group which it resembles both morphologically and physiologically The value of this pnnaple for (he correlauon of facts is far greater for the student than the question of its worth as a philosophical explanation of ontogenies

It must be staled that the authors are under no illusion that the subject of comparauve vertebrate development can be adequately presented in a book of this character However some of the more fundamental facts especially those relating to early stages of development




will be given. It is hoped that the brief presentation of these facts will help to make more clear and meaningful many otherwise uncorrelated phenomena of human development, and that they will at the same time stimulate interest in the general field of embryology,


There are significant differences in the morphology and physiology of the germ cells of various vertebrate species just as there are differences between adults of the species. But as the germ cells are relatively simple structural and functional units compared with adults, the apparent differences are neither as numerous nor as extensive. Both male and female germ cells are nevertheless highly specialized and their structure is adapted to, or determined by, the functions they perform The sperm cells are more likely to possess visible distinctive characters than are the ova , but most of these sperm peculiarities are of no known significance It IS generally believed that their morphological traits are chiefly adaptations to the particular problems which they must solve in reaching and penetrating the ova. In order to accomplish this function the amount of cytoplasm in a sperm is reduced to a minimum, a flagellum is oes^loped tvhich renders it highly motile and the sperm head frequently possesses a special mechanism for the perforation of the ovum and its membranes. After fertilization, sperm morphology does not appear to be concerned with the further development of the embryo, although the genetic structure of the male gametes is of fundamental importance.

Ova, on the other hand, are always distinctly larger cells than the normal somatic cells of the organism from which they are derived. Further their increased cytoplasmic mass is frequently enormously enlarged by the accumulation of yolk oi deutoplasm (Fig. 410). They frequently possess protective envelopes, or egg membranes, and owing to the absence of motile organs they can only be moved passively. The size of ripe vertebrate ova, excluding their membranes, range from a diameter of about loop. in Amphtoxus and eutherian mammals (range 80-150/i) to about 85 mm. m the ostrich. The structure of an ovum, especially the degree to which nutrient material is included in its cytoplasm, has a marked effect on early development. Yolk-rich (megaleathal — mega = muc , lecithal = yolk) eggs support embryonic development of a vegetative sort to a relatively late stage; yolk-poor (mwlecithal ^m(e)io — less) eggs can do this only for a very short time, after which the embryo must acquire means 0 obtaining its nourishment from outside itself be that from sea water, soil, the tissue of a ost or the mammalian uterine mucous membrane.

The primitive Metazoan reproductive method appears to have been one in which a large number of miolecithal eggs ivere produced and widely dispersed. With little stored materia an early larval, or free-living embryonic stage, was necessary. In vertebrate evolution t tendency was to increase egg size and reduce the number of eggs laid. This tendency was associated ^v'lth the prolongation of the developmental period as in reptiles and birds w ere a larval stage is suppressed. In the mammalian class the evolution of specialized viviparo mechanisms has resulted in egg size being secondarily reduced, only slightly in Monotrem but markedly in Euthena. . r

Ov'a can be classified, therefore, on the basis of the relative amounts and distnbution 0 yolk and cytoplasm within them Table IV is designed to present this classification and correlate vertebrate ovum types with cleavage types Like all classifications this is for co • venience, and there are intermediate ova and cleavage types which do not quite con 0 to any compartment in the scheme. The most complete intergradation is miolecithal and medialecithal types. A fairly well marked gap exists between the medialcc and megalecithal eggs, but even here a few transitional types are kno^cn (eggs o P Lepidosteidae ) .

Fig. 410 — Schematic section of mature amphibian egg


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\s has been described on paijc fa deisn^c i* the process wJjerebt the protoplasmic rnass of the fertilized efc,t, is pirlitioncd (either completel) or mcomplctel> ) into cells of il)out the size normal for the particular species Ostini, to the hrge size it is Iikcl> tint the unfertilized egg IS in an ibnonmJ metabolic state As clctsage progresses tlic diminution m cell size ol the successisc generations ofbhstomcrcs establishes gncluallj normal metabolic conditions ^ncomitant with tlic diminution in cell size greater mobilit) is conferred on the mdisidual hlastomeres thus facihnting liter morphogenetic mosements (see gastnihtion page 383) and


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m those eggs with gross accumulation of deutoplasm this material is gradually extruded from the effective protoplasmic mass.

Cleavage may be classified either in relation to the fate of the resulting blastomeres in subsequent development or, descriptively, in accord with the actual pattern of the cellular divisions Utilizing the former method cleavage is either determinate or indeterminate. Ova ■with determinate cleavage are those (mosaic eggs) in which the organ-forming regions are already predelineated m the fertilized egg. Indeterminate ova, which are usual in vertebrates, are those in ^vhlch there is no obvious mosaic structure at the time of fertilization and it is only after a certain, and generally quite late, stage of cleavage that presumptive organ regions are established. Up to this stage the blastomeres are pluripotent and are not yet “determined” (see page 121) so that, unlike the blastomeres in determinate cleavage, their prospective potency IS not necessarily identical with their actual developmental fate This implies that such

blastomeres possess certain poweis of adaptation to changes in their cellular environment, and consequently, eggs showing this type of cleavage are often called regulative eggs.

purely descriptive classification of cleavage is 1 elated to ^ actual pattern of the cell divisions. This pattern is largely

Ll .5 y dependent on the amount and distribution of the stored

JrC deutoplasm and thus the type of cleavage is related to the initial

size of the egg and varies according to ^vhether the eggs are niiolecithal, medialecithal or megalecithal (Table IV).


^ ^ In these eggs the first cleavage spindle forms near the centie

of the egg so that two equal-sized blastomeres are formed

  • (complete (holoblastic) and equal cleavage). These blastomeres

/' in turn divide equally and successive equivalent divisions of the

^ daughter cells result in the formation of a morula made up 0

many cells of nearly equal size and containing neaily equa ( ^ amounts of yolk and cytoplasm. In practically all these

Vsi ’■‘tl miolecithal eggs, however, there is a slight difference in blasto mere size and quality after the third cleavage. In Amphioxus after this third (equatorial) cleavage the four cells at the so-ca e

“animal” pole are slightly smaller than the four at the

n pole. Subsequent divisions emphasize this difference so t at t e „ , morula (Fig. 411) possesses an “animal” pole with smaller ce s

tion of mature'"^cgg **^0? ^ “vegetal pole” "wnth larger cells. Even P f

Amphtoxus B Early blastula mammals some difference m blastomere size is usually detecta

early in cleavage (Figs 28 and 412)


In these eggs with a moderate amount of yolk the first two cleavages ordinarily ^ our equa astomeres, but the third cuts off animal pole cells which are much sma er ose e t at the vegetal pole (complete and unequal cleavage) Moreover, the sma con am itt e yolk, while the vegetal cells are loaded with it. This inert nutritive ma 'eeps ^ e metabolic rate of these vegetal pole cells relatively lower than that of the anima p’oup, e ^tter, therefore, divide much more rapidly and so assume the „igte

formation of the embryo The most familiar examples of medialecithal ova with complete u unequa c eavage are amphibian eggs, especially those of frogs and toads (Fig- 4 U


tb ^ megalecithal eggs of reptiles, birds and the egg-laying mammals {Monotremata) ^^P the greatest development of yolk storage. Sharks and Lyt {Euselaehn) have almost as mu

I'lG 411 — A Schematic section of mature egg of Amphtoxus B Early blastula of Amphtoxus


^olW, while the bon> fishes {T<Uostei) have notice ^

abh less but still enoutjh to limit cleavage to the | ,

mcomplece type In megalccithal eggs the active ( ^

egg cytoplasm with Us nucleus is a relatively ’

minute mass at the animal pole of the heavily ‘ F )\ 1

yolked egg Cleavage is at first equal but only f ^

involves the active cytoplasmic region The yolk j f \ '1

mass does not divide but is graduallv used as ^ I 1 I*

pabulum for the embryo and the extra embryonic ‘ ^ i ‘

membranes derived from the cells of the animal , j^r * jj ^

pole This incomplete partial or discotdal type of j

cleavage (meroblastic) results m a disc shaped \ ' j

morula and blastula instead of the essentialK v •* /

spherical structures seen in all the previously n.

mentioned types (cf Figs 415 417 and 419) ^ ^ TT % ^

In the phylum Chordata the miolecithal ^ ^ ^ ^

medialecithal and megalccithal types are all

found although the latter two are the more Fic 412 —A living morula of sheep killed five ° _ , , , , ^ ... days after mating x 380 (Reproduced

common The (^ephalochordata possess miolccitnal from Physiology of Reproduction by per

eggs with nearly equal complete cleavage In the mission of Messrs Longmans Green & Co

C}closlemala the pelr<}iin.,onU have medialecithal ova vvith unequal complete cleavage while the

mytinoids have megalecithal eggs wath incomplete cleavage Among the fishes the sharks and rays {Eusilachi) have megalecithal eggs unth incomplete cleavage The Poljplertdae the CkondrosUt the holostean Imia (i e , the group formerly called the ganoids) the Dipnoi (lung fishes) and the Holoeepkali have medialecithal eggs with unequal compleic cleavage The eggs of the holostean Lepidosteus (also a ganoid form) are transitional m type having so much yolk that cleavage is never complete yet m general pattern 1$ more like the unequal complete type than the discoid The true bony fishes (formerly grouped together as TtUostei) have relativclv small megalecithal eggs with defimtelv discoid cleavage Amphibia are characterized by

Frc 413— Section of an early blastocyst of the golden ham ster Cruttus au alus The outer cells are developing to form the trophoblast which is more darkly jtained than the cen trally placed cells x 640

(Reproduced from Physiology of Reproduction bv per

mission of NIessrs Longmans Green &, Co Ltd )

medialecithal eggs and complete but unequal cleavage Here the Apoda (Gjmnophionia) arc exceptions having so much yolk that their eggs should be classed as megalecithal with incom pletc cleavage AU reptiles and birds have large megalccithal eggs with incomplete cleavage All marsupials (Mctalhena) and placental mammals (Euthcria) have miolecithal eggs with complete and almost equal cleavage The reJalive ahscnce of yolk in both Metathena and Euthena is considered by some to represent a revcoal m evolution from the ^gs of ancestral oviparous reptile like mammals which undoubtedly possessed megalccithal ova The eggs of marsupials contain rather more yolk than do those of placental mammals, and yolk bearing fragments are commonly eliminated during cleavage {deutoplasmolysu) This phenomenon may represent a stage in adapution to viviparity The rare egg laying mammals (Monotremata or Protothena) have megalecithal ova with discoid cleavage (Caldwell, 1884 Flymn and Hill 1939 1947) There is now an extensive literature concerning the mechanism of cleavage the rates of cleavage in different animal groups and the effects of cbcimca! substances, especivlly mitotic poisons on cleavage This has been summarized by Boyd and Hamilton (19^2)



- c:

Fig 414 A Section of sheep blastocyst 10 days post insemination The endoderm can be seen lining the upper half of the blastocyst cavity X 230

B Section through inner cell mass region of another sheep blastocyst at the 10th day The inner cell mass is becoming intercalated into the trophoblast x 230.

C Section of embryonic disc of a sheep blastoc%st 12 days post insemination The embryonic formative ectoderm is now bulging above the lc\el of the adjacent trophoblast x 280

(Reproduced from “Physiology of Reproducnon,” by permission of Messrs Longmans Green & Co , Ltd )

In miolecithal eggs the blaslula is the hollow sphere of cells which results from the process of cleavage. The cavity of the blastula {blastocode) IS enclosed by cells which are slightly smaller m the animal than in the vegetal hemisphere (Fig. 41 7A), In medialecithal eggs the blastocoele is relatively small and, since the animal pole cells are definitely smaller than those in the vegetal portion of the sphere, the blastocoele cavity is much nearei the animal pole (Fig. 417®)* no longer speak of animal and vegetal hemispheres, but rather of an animal portion (usually about one-third) and a much larger vegetal portion. In megalecithal eggs the blastula is merely' a thin flattened disc of cells resting on the yolk mass, but separated from the yolk, except at its margin, by a shallmv cleft-like blastocoele (Fig. 419).

Although the mammalian egg is relatively yolk-poor and cleavage is at first complete and nearly equal, the late morula and blastula are distinctly different from those of lower vertebrates with miolecithal ova (e.g., Amphioxus). In the mammalian moiula an outei layer of small, slightly flattened cells can be distinguished from the larger polyhedral ce s of the inner cell mass This outer layer is t e trophoblast or trophoblastic ectoderm (

33i 34i 35i 56 and 4i3)- The blastula caw^^^ appears between the trophoblast and t cell mass and separates them side where they remain m contact. This yp of blastula, which is peculiar to the eutberia mammals, is probably not quite compara e the blastulae of lower forms, and part y or reason it has long been called a '^1^ *„ei The eggs of marsupials are slightly la g and more yolk-laden than those o p «  mammals and they diffeientiate more ra so that blastocyst formation is not qui same. Hill (1918), Hartman (1920), (1934) and McCrady 'SjS an ,,,

shown that in several of these ( Dasyurus, Macropus and Perameles) true morula, for, after the second blastomeres arrange themselves 1 layer around the inner surace „ ^12) pellucida, forming a hollow sphe ( g- j Lh eliminated yolk-fra^ents m the cc" cavity. This is a typical blastula and


blaslocjst for ihrro ,s no inner cell mas Certain largercells at the animal |»le (formatne area) m,™ie innards to form the endodem. (n)-nn and Hill 19(0) In the insectirores HmictnleUs stmtspinosus (Goetz, 1938) and Btphanlulus Jamesonu (van der Horst 1942)

a smeic lavered blastula ( mammalian blastula ) is formed without an intervening morula stage and at first without an inner cell mass \toncpolc however, a thickening resembling an inner cell mass, soon appears This is perhaps caused b> dehmination of an

inner cell mass in the true sense It is conceivable therefore that the **

marsupials and certain inscciivorcs show some of the transitional steps leading up to the typical mammalian blastocyst / ra-V

There is considerable variation in the relation of the trophoblast "f> to the mner cell mass ( formative cells ) in the stages immcdiatclv following the formation of the blastocyst m the different cuthenan groups In some e g , pnmates (probably including man) bats and a .

most rodents the trophoblast at first complcieK covets the tnner cell <

mass (Figs 56 58 and 428) In others like the pn, and probablv most of the ruminants and carnivores, the trophoblastic cells (Raubtr s laitr) covering the inner cell mass soon disappear exposing on the surface the cmbrvonic ectodermal portion of the inner cell mass This remains exposed until the amniotic folds form at a later stage


The Metazoan embryo at the end of cleavage (1 c in the blasiula B stage) undergoes a rapid change m shape due to a complex rearrange ment of the constituent cells This arrangement results in the establishment of the germ layers and is essentially a process enabling presumptive organs to reach (iieir correct position (RabI 1915 \ ogt 1929 Lehmann 1945) It is called ^af/ri/fa/ion The nature extent ^ and chronology of the gasiruiation movements IS different m different J species but thev always precede by a little the appearance of the 5 us ii

primordial organs In the mammals the process is delayed and when It occurs IS restricted to the formative cells of the inner cell mass The simplest form of gastrula is an embryo with only tvvo germ layers ^ an outer xhe ectoderm and an inner the rniAx/rm (Pig 415) The term gastrulation is often defined as the process by which the single lavered ^

blastula IS converted into a two-layered gastrula Tins is an adequate ' TT S

definition for a stage m many invertebrate types eg the miolecithal eggs of CoelenUrata and Cchnodermata as it desenbes a liurlv definite r'

period m development for these eggs owing to their complete and ::

nearly equal cleavage produce blastulac which are hollow spheres ^

with the cells of the vegetal hemisphere only slightly larger and more yolk laden than those of the animal hemisphere Xmphioxus possesses a q "■Xr?— t_i-J^ similar blastula (Fig 415)


4'5 — Semi schemaiic drawings lo sho» gasiruiation and chorda mesoderm lormation in Imphtorus (Based partly on Conklin 1933 ) Ectoderm and neural tube in section in blue Endoderm in yellow Chorda mesoderm and oelinitvc chorda in reverse red sCipple Unsectioned mesodermal cells are shown with red stipple

' Late blastula stage (longitudinal seclionl B Earl) gastrula stage (longitudinal section)

^ Late gastrula stage (longitudinal s ction;

U Early mesodermal diverticula stage (transverse section)

h Definitive coclomic pouch stage (transverse section)

the arrow in A represents the future amcro posterior ams of the embrvo



In order to understand the morphogenetic movements occurring at gastrulation it is necessary to know the position of the presumptive organ-forming areas in the late blastula stage. Maps (Fig. 418) showing these areas have been provided for amphibian eggs by a number of investigators who have applied coloured marks to portions of such eggs and followed the fate of the stained regions in subsequent development (Vogt, 1925 and 1929)


The blastulae derived from miolecithal eggs gastrulate by invagination of the vegetal hemisphere into the animal hemisphere, thus obliterating the blastocoele and forming a new


Fig 416 — Schemes to shotv the relation of the amnion and chorion to the somatopleure

A — Cross section of a typical vertebrate embryo in the region of the fore or the (q

B — Cross section of a typical mediolecithal vertebrate embryo in the region of the yo m show the potential “yolk sac ” gj

C Cross section of a typical anamniote vertebrate embryo of the megalecithal group, of a teleost, to show the trilaminar yolk sac. tvpic^^

D, E and F — Cross sections of successive stages in the development of the nsing

ammote vertebrate such as a reptile In these three schemes the amniotic folds are s from the extra-embryonic somatopleure

  • ted

cavity, the gastrocoele (also called the archenteron or primitive gut), lined by the ^ q’jje cells which constitute the primary endoderm. The outer layer of cells is now the ^ blastopof^ circular opening, where the latter is continuous with the mvaginated endoderm, is tn In the Coelenterata the gastrula develops into the adult without any fundament in its morphology Even in the Echinodermata and Amphioxus the embryo retains i gastrula form for an appreciable time, becoming motile and feeding during ^ .jefly at was formerly held that these simple gastrulae grow in length by cell multiplication the nm of the blastopore. This rim was regarded as an undifferentiated area, an cells believed to arise there were considered to become ectoderm if they happenea



cMcrmI to the nm or cnclodcrm if just intcmil to it More recent work howescr ind especiall> the results of mappint, has shown tint the cells of the bhstuh ln\e a prospectisc su’nific'ince licforc Ristnihtion I he chaOsCs it the hlxstoporic hp therefore in%ol\c extensive migratory movements nlhcr than simple proliferation Indeed in \wphtovus a.s subsequent development showa (Conklin 1932) the invat,inated inatcria! includes more than the primary endoderm (I ig 415) as it also gives to the third germ lajer (tlie mesoderm and notochord) In all vertebrates inv agination of the primary endoderm precedes bv onlv a bncf penod the invagination of mesoderm and notochord m fact the three processes occur more or less concurrently In verte brales then there is no clear distinction between the period or the process of formation of cnthxlcrm mesotlcrm and notochord there fore It IS liecoming common practice for vertebrate embryologists to include as gastrulation not onlv the process of endoderm formation but also that of the early formation of mesoderm and notochord for the sake of continuity the origin of the somites coelom and neural plate will lie discussed here although these processes arc not even in a general seme a part of gastrulalion

Careful study of the growing gastnila of Impktotus reveals that the invaginated vegetal hemisphere cells form onlv that endoderm which lines the floor and approximately the lower lsvo.tJurds of the lateral sides of the elongating gasirocoelc or primitive gut 1 his primarv endoderm is augmented by secondaty endoderm or thorda mtsodem consisting of small yolk free cells (Pig 4J5) which migrate in through and proliferate from the region of the blastopore ami form the roof and upper tliird of the sides of the primitive gut This chorda mesoderm is not considered to contribute much to the definitive gut It is really a stage m tlic denvalion of the mesoderm and notochord from the cctodenn In this process the chorda rneso* derm along the midline of the roof of the gastrocoeic cvaginalcs dorsal ward forming a ridge wliicli soon separates from the gut l>eginning at the cephalic end and forms a solid rod of tissue the notoihord At the same time lateral diverticula (the mesodemie or totlomic pouches) ansc in consecutive pairs from the lateral part of the chorda mesoderm on either side of the notochord cv agination The first pair

appear at the anterior (head) end and the succeeding ones, m sequence back towards the blastopore I he pouches enlarge, separating the ectoderm from tlic primitive gut and finally sever their own connection with the gut cavity and endoderm Thus a senes of isolated paired mesodermal sacs enclosing paired cocinmic cavities arc formed throughout the length of the embryo (Pig 4i5r) Phev expand ventrally and dorsally separating the cndodcrmal gut completely from the ectoderm Along the mid sagittal plane where the adjacent portions of right and left mesodermal pouches come into contact

ventral and dorsal to the gut they form the temporary ventral and permanent dorsal mesentery Tig 416) The lateral portion of the

Fio 417 — Semi schemaiic drawings to show Kastnilation and chorda mesoderm formation in Amphibia The same conventions are adopted as m I ig 415 \ Cleavage stage B Section of cleavage stage C Tarly gastrula stage (longitudinal section)

D Intermediate gastrula stage (longiludinal section)

E Late gastrula stage (longitudinal section)



mesoderm of each pouch comes into contact with the ectoderm and becomes mainly translormed into a segment of the body musculature, the medial portion, m contact with the endoderm, forms the smooth muscle and connective tissue of the alimentary tract and mesenteries Probably relatively little of the chorda-mesoderm remains after formation of the notochord and mesoderm.

any which persists is found as a median strip m the roof of the definitive gut cavity. The processes just described constitute the fundamental steps in the segregation and differentiation of ectoderm, endoderm, mesoderm and notochord.


Gastrulation in the medialecithal ova of the lampreys {Petromyzontidae), certain of the “ganoid” fishes (Polyptendae, Chondrosiei, Atniidae) and the Amphibia is typified by that of the frog although, of course, there are variations in detail. In the frog


Fig 418 — Scmi-schematic drawing to show primiU\c streak stages

.\ Late gastrula

stage through pnmiUve

streak (trans\ ersc sec tion)

B Farlj ncurula

(trans\ersc section)

C Formation of neural folds (surface vnew) D. Prcsumptite regions on the surface of the hlastula

(Fig. 417) the relatively great size and slow cleavage rate of the yolkladen blastomeres in the vegetal two-thirds of the blastula is the chief cause of differences in its gastrulation from that of such forms as Amphioxus. As the large cells form too bulky a mass to be mvagmated within the fewer and smaller cells of the animal pole, gastrulation is effected by the proliferation and spreading of the smaller animal pole cells downwards and over those of the vegetal pole while, at the same time, the animal pole cells of the advancing margin are progressively mvagmated so that a new cavity (the gastrocoele) which communicates with the exterior is formed, and the original segmentation cavity is obhteiated The gastrocoele is partially lined by animal pole cells (chorda-mesoderm or secondary endoderm) in addition to the heavily yolked cells of the original vegetal pole (primary endoderm) The former will give origin to the mesoderm and notochord. Those animal pole cells which are never mvagmated (1 e , those furthest from the area of invagination) will in later stages form the definitive ectoderm and neural plate The process of spreading, or overgrowth, by the smaller animal pole cells, is called epiboly It commences at the margin of the animal hemisphere and from the first shows a bilateral symmetry, the- overgrowth is more rapid at the future cephalic margin [dorsal lip) of the blastopore and slower at the future caudal margin [ventral lip) , the marginal regions joining the dorsal and ventral lips are the lateral lips and they show a dorso-ventral gradient in the degree of overgrowth. The entire margin of overgrowth is the blastopore As epiboly nears completion the blastopore becomes a small circular opening plugged with buried endoderm cells. This is known as the yolk plug and is of little significance except as a characteristic condition at one period in the gastrulation of most medialecithal eggs of vertebrates The original yolk-laden cells of the vegetal two-thirds of the blastula now form a mass within the ectodermal shell and beneath the sht-hke gastrocoele which lies between the mvagmated chorda-mesoderm and the primary endoderm The chorda-mesoderm is continuous with this primary endoderm cranially, and temporarily forms the roof and upper lateral portions of the gastrocoele or primitive gut cavity With continued development the periphery of the mvagmated chorda-mesoderm extends ventrally on the lateral side of the primary endoderm At the same time the upper edges of t e latter extend medially and eventually fuse in the mid-hne an



undemcith the axial portion of the chorda mesoderm This axial portion is the notochordal plate and as it is separated from the roof of the I'astrocoelc it becomes the notochord The fused edges of the primary endoderm underlnni, the notochord form the permanent roof of the enteron or gut Lnlike Im/Aiono mesodermal pouches are not formed b> csagination from the chorda mesoderm The mesodermal sheet mcrcl> extends \entrall} between the endoderm and the o\crl\ing ectoderm Mesoderm formation begins in the late >olk plug stage as the blastopore is constricting to form a \erucal dumb bell shaped slit The lower end of this slit remains open as the definitive anus the upper end persists tcmporanl) as a duct xhc neurenltrie eanat leading from the caudal end of the ectodermal neural groove into the gut just caudal to the point where the secondarv endoderm and notocliordal plate are still con iinuous Between these two openings tlic lateral lips of the blastopore fuse and from this fusion line or e streak the mesodermal sliect

continues to be proliferated from the ectoderm and extends laterally and anteriorly on each side of the notochord As each sheet grows laterally it separates the ectoderm from the cndoticrm until finally as in Imp/uoxus the sheets meet ventral to the gut (Fig ji8\andB)

The further differentiation of the mesodermal somites lateral plate mesoderm and coelom is typical of that of most vertebrates

GASTRULATION IN MEGALECtTIlAL EGGS Fishes The process of gasinilation in vertebrate mcgalecithal eggs vanes with the amount of yolk relative to the cytoplasm In the Teleostet (bony fishes) the cytoplasmic area is relatively large compared w ilh that of sauropstdan (reptiles and birds) eggs After early cleav age in the telcosts the blastoderm usually covers about one fifth of the surface of the egg \t the margins of the blastodtse the deeper cells separate (by delamination) from the outer thus forming a circular zone of primary or yolk endoderm \t about the same lime liouever a definite inturning (invagination) of the surface cells begins at the caudal margin of the disc to form a layer of secondary endoderm (chorda mesoderm) corresponding to that of Amphtoxur and the \mphibia This spreads rapidlv over the upper surface of the yolk separating it from the overly ing ectoderm and fusing on all sides with the marginal yolk endoderm As this overgrowth continues its rim passes the equator of the egg and constricts on the caudal side of the vegetal pole to form a somewhat circular opening which is readily recognized as the blastopore \Nhen this process is ncarlv complclcd the two layered blastoderm grows downwards and envelops the yolk mass to form the bilaminar yolk sac which is part of the primitive gut and characteristic of all mcgalecithal vcrlcbrales Tlie invagination

Flo 419 — Srmi schematic dras mgs in shos gasinilation and chorda mesoderm formation in the asian egg

\ Germinal d sc \ ith w o polar bodies B Lateral surface lies of early biaslixlisc C Longitudinal section through early I lastodisc

D Longitu I nal section through later blastodi c (The arrows in the inset show the direction of migration of the mesoderm )

E Farlv gastrula stage {longitudinal section^

F I resumptiie regions in the surface of Ihe blastoderm (superior view)

G Presumptiie regions in the surface of the blasiodeim (lateral vies )

H Transverse section through late gastrula stage in region of notochordal plate

I Transverse section at level of primitive streak



at the blastopore is much more marked, and the primitive streak persists for a longer time than in the frog. The process of primitive streak formation is still active and the blastopore is still open even after the formation of the head fold and many somites. The notochord and mesodeim arise much as in the frog, the former by invagination of the chorda-mesoderm through the doisal hp of the blastopore (primitive node) and the latter by invagination of surface cells thiough the primitive streak (fused lateral lips of the blastopore).

Reptilia. Owing to the still greater proportion of yolk m the reptilian egg, gastrulation IS even less like that of the frog than is that of the Teleostei The blastodisc is a relatively small aiea on the huge yolk mass, and the segmentation cavity is insignificant. Under the entire blastoderm yolk endoderm cells separate from the surface cells (ectoderm) and orgamze to form a complete sheet of primary endoderm. The two-layered disc now begins to overgrow the yolk, as in the fishes, and at the same time a small depression forms on its surface near the ( audal margin. This is an area of invagination, the dorsal hp of the blastopore. There is a convergence of surface cells towards this area and a short primitive streak or “plate” is formed, ■d though apparently no such movement of the actual edge of the bilaminar disc occurs, as ,n the fishes From this the notochord and mesoderm arise as in the Fishes and Amphibia.

Peter (1935), however, considers that in the chameleon and lizard most of the notochord and gut endoderm is formed from the delaminated yolk endoderm, only the caudal portions of each arising from the invaginated chorda-mesoderm (see also Pasteels, 1937 and 1940).

Aves. Cleavage and blastoderm formation in birds are almost identical with these processes in reptiles. There is a blastula stage in which the cleavage cells form a blastoderm three or four cells thick, separated by a shallow “segmentation” or “subgerminal” cavity from the centrally placed yolk and continuous with it at the periphery. The central, unattached region is the area pellucida, the attached margin, the area opaca. Around the margin, yolk endoderm delaminates from the overlying ectoderm as m reptiles. According to the usual description, based largely on Patterson’s (1909) investigation of the pigeon, the caudal margin of the blastoderm invaginates to form secondary endoderm much as in the bony fishes. Convergence of the blastoporic lips gives rise to a distinct primitive streak, and it is during the initiation of this process that the blastopore is closed (Fig 419). Jacobson (1938) believes that much of the foregoing description of gastrulation m birds requires modification He states that there is practically no segmentation cavity and that there is a very brief period when the area pellucida of the blastula is made up of a single cell layer He considers that there is no invagination of the caudal edge of the blastoderm to form a temporary blastopore Instead, there IS an o\'al area of the caudal region of the area pellucida, not involving the margin of the disc, from which individual cells migrate beneath the blastoderm, proliferate, and organize to form a sheet of secondary endoderm which soon spreads out like that of the reptiles and bony fishes to fuse with the marginal yolk endoderm This area is the primitive blastoporal plate and coriesponds to the dorsal lip of the blastopore, although there is no invagination. There follows a movement of surface cells toivards the plate, and the area caudal to it, which is comparable to convergence in the t^qies previously described. These cells form a definite primitive streak from the lower surface of which, for a short time, endoderm continues to be budded Soon, however, all the cells proliferated laterally from the streak he between the ectoderm and endoderm and are, therefore, mesoderm (Fig. 420). From the cephalic end of the streak the notochord arises m the usual manner, being first included, as a notochordal plate, in the roof of the primitive gut, and later separating from it to assume its typical position between the gut and the central

Fro 420 — Schematic representation of the surface view of the developing blastoderm in the chick embrj’o The area vasculosa IS represented in red dots.



nen'ous system (Fig 42 1) More recently Pasleels (1945) Has rein\ estigated the origin of the avaan endoderm In the duck he found the primary cndoderm to arise as the result of the progressive delamination of the dealing blastodisc into a superficial and a deep layer between which a cleft appears He homologizes this cleft with the blastococle and considers that the sub germinal cavity IS not a blastococle being infact only theresuk of theprogressiveliquefaction of the yolk acted upon by enzymes produced by the yolk syncytium and perhaps the blastoderm itself


Up to the present it has not been possible to make an adequate experimental analysis of the process of gastrulation m the mammals The precocious segregation of tissue regarded as ectodermal to form the trophoblast limits the formation of the endoderm and the intra embryome mesoderm to a restncied group of cells in the typical euthenan blastocyst Earlier investigators (e g Keihel 1889 and Hubrecht, 1890) thought that mammalian gastrulation occurred m two stages The first of these is the formation of primary endoderm by delamma lion of cells from the inner cell mass or ils equivalent and the second the imagination of embry oruc disc cells to form secondary endoderm mesoderm and notochord Most modern investigators necessarily basing tbeir conclusions on morphological findings regard both the processes as essentially part of gastrulation though invagination is much modified and reduced Endoderm formation in all mammals IS basically similar to that m the avian egg in that cells migrate or are delaminated from the deep surface of the inner cell mass (Fig 414) These endodermal cells may in part become intimately related to the trophoblast in the formation of the yolk sac but there is no reason to doubt that their initial formation is an integral part of gastrulation In the second stage of gastrulation there is a migration of surface ectodermal disc cells to a limited axial region of the posterior portion of the embryonic disc to form the primitive streak From tins streak cells come to he between the embryonic disc ectoderm and the endoderm to form the intra embryonic mesoderm (and in many species by later extension the extra embryonic) The anterior extrcmitv of the pnmuive streak is specialized to form the primitive or Hensen s node Some of the cells of this node form an invagination which gives origin to the notochordal or head process as described in human development (page 49I This notochordal process becomes temporarily intercalated in the axial region of the endoderm hut later separates from it to form the notochord In addition to the formation of mesoderm from the primitive streak as an integral part of gastrulation mesoderm can also arise from the trophoblast (extra embryonic mesoderm) from the prochordal plate (cephalic mesoderm) and from the neural crest (page 270) The theoretical consequences of these additional methods of mesoderm formation on our conception of gastrulation are not vet clearly understood For details of gastrulation in marsupials the reader is referred to I Ivnn and Hill (1942) and McCrady (1938 and 1944)


As has been stated earlier (page 69) a structure or tissue developed from the fertilized egg that does not enter into the formation of the embryonic body is called an (extra )embryonic or foetal membrane These membranes are of functional importance during embryonic hfe being concerned with the supply or storage of nutriment respiratory txchange and protection oftheembryo They arelargely shed or absorbed at hatching or birth The foetal membranes include the_job sac the chorion (or serosa) the amnion, the allantois the trophohlasl (m mammals) the piacinia and the orn6jfif<3l cord Certain of them are not necessarily membranous m character

Flo 431 — Section of somite stage of (he de veloping chick embryo to show formation of amniotic caviw and formation of >oIk sac and extra embryonic coelom



(e.g. many placentae and the umbilical cord). In many mammals (deciduate types) the uterine tissues come to be intimately connected with the outermost embryonic membranes (page 67).


The cyclostomes, fishes and amphibia do not possess an amnion and are consequently known as the Anamniota, In the embryos of these vertebrates the only embryonic membrane developed is the yolk sac This sac, whether in the form of a definitive yolk sac (e g., m the megalecithal eggs of the hag-fish, the sharks and the bony fishes, Fig 41 6G) or of a mass of heavily yolked cells (e.g , in frog, Fig 416B), is enclosed within the ventral wall of the body In theforms with a definitive yolk sac during orsoon after gastrulation the ectoderm, mesoderm and endoderm of the embryonic disc grow down over the yolk mass, thus enclosing it within the primitive gut and body wall. This three-layered (trilaminar) yolk sac wall has exactly the same fundamental structure as the gut and abdominal wmll of the frog embryo at about the time of closure of the neural groove The only difference is that in the frog the yolk material is intracellular, within the endoderm cells of the gut (Fig. 416B), whereas in the megalecithal species it is in the form of a relatively large non-cellular mass lying within the gut cavity and distending the whole “abdomen” far beyond the normal body contours (Fig. 41 6C) In these trilaminar yolk sacs the mesoderm becomes very vascular and gradually transports the nutritive material, absorbed from the yolk by the endoderm, to the growing tissues of the embryo proper. Thus the yolk sac shrinks as the body grows, and finally becomes incorporated into the ventral abdominal w^all and gut Its tissues are not only homologous with those of the gut wall and body ^vall, but they actually become part of these structures.

Some Euselachii are viviparous, and in these the yolk sac wall functions both to absorb the yolk through the endoderm and to absorb oxygen and nutriment through its ectoderm from the uterine wall of the mother This is a type of yolk sac placentation, and in some species It consists of a fairly close apposition of the yolk sac wall to the uterine lining (Gate-Hoedemaker, ’^933)* III the relatively rare viviparous bony fishes the yolk sac is usually very small as the eggs themselves approach the medialecithal type In these, therefore, no yolk sac placenta is formed, but absorption from the maternal tissues is carried on by vessels of an excessively enlarged pericardium or by special modifications of gill or anal filaments (Turner, 1940)


Most of the anamniota discussed above deposit their eggs in water, but there are other groups of megalecithal vertebrates {Reptiha, Aves and Monotrematd) which lay their eggs on land These are all characterized by the presence of an amnion, a modification of the extraembryonic body wall (somatopleure) to form a liquid-filled cavity, surrounding the embryo (Figs 416E and F and 422). The most obvious purpose of the amniotic cavity is to provide a local aquatic habitat for the embryo in eggs laid in non-aquatic surroundings The amnion develops before the embryonic body is definitely formed and persists, in these types, until hatching. The ev'olution of the amnion is uncertain, but its probable primitive manner of formation is showm in Fig. 41 6E and F. The chorion, or serosa, is formed during the closure of the amniotic folds from that part of the extra-embryonic body wall which does not contribute to the amnion (Fig. 423) • The development of the extra-embryonic coelom completely or incompletely separates the non-amniotic somatopleure, consisting of extra-embryomc ectoderm and its lining of (somatoplcuric) mesoderm from the splanchnopleure formed by the extra-embryonic endoderm and its covering of (splanchnopleuric) mesoderm This portion of the extra-embryonic somatopleure is the chorion The extra-embryonic endoderm and its covering splanchnopleuric mesoderm form the bilaminar splanchnopleuric yolk sac The chorion and the splanchnopleuric yolk sac are structures not found as such in the aquatic egg types, but nevertheless they are represente in the latter by the somatopleuric and splanchnopleuric layers of the anammote yolk sac (Fig. 41 6C).




This structure is a special precocious!} dcselopcd embr\omc membnne found m the desclopmenl of Metathcna (marsupials) and Emhcna The primara object of this membrane








IS the formation of a vesicle capable of absorbing nutritive material and, by its rapid growth, the provision of a space m which the embryo can grow and differentiate


In viviparous mammals an amnion is always developed and in its definitive stage of development is essentially similar in all metathenan and eutherian groups although it originates

m different ways. The most primitive method of amniogenesis would seem to be by folding of the extra-embryonic somatopleure, as has been described above for the megalecithal amniotes. There are all gradations from this method of amniogenesis to that of such species as the monkey or man, m which the amniotic cavity arises by a cavitation of the inner cell mass as a result of the confluence of intercellular spaces in that part of it related to the covering trophoblast. In some mammals, e.g., carnivores and ungulates (Fig 422), showing amnion formation by folding, the trophoblast over the embryonic disc becomes a thin membrane (known as Rauber’s layer) and disappears, leaving the embryonic disc secondarily intercalated in the wall of the blastocyst and thus exposed until the amnion is formed In many bats (Fig. 422) an ectotrophoblastic cavity appears between the trophoblast and the embryonic disc ectoderm, the definitive amnion IS formed later by folding within this space. In many rodents (Fig. 422) the trophoblast covering the inner cell mass proliferates an , at the same time, the inner cell mass is invaginated into the yolk sac This condition, especially when it occurs at the embryonic isc stage, IS known as “inversion” or entypy 0 the germ layers. The proliferating column o trophoblast is called the “carrier, or rager. The space enclosed by the embryonic disc and the cells of the Trager is the pro-ammotic space. This space is divided by the development o amniotic folds, into a lower amniotic ^ and an upper epamniotic (ectoplacental) cavi y.

In rodents with superficial implantation only partially interstitial implantation

formation IS by simple folding. Thus m with partially interstitial (intramural) imp a tion of a large blastocyst where the uteri epithelium does not grow over disc at the site of penetration, the a develops by folding (Figs 428 an 433 h

The later htstory of the amn,on ar « 





Fig. 423 embryonic

/ -- |Vlossman

■Three stages in the development of the considerably as ^as een ® ^ independent

ic membranes of the chick. (l937)' remain. G/



non \ascubr membrane until fuW term as tn roost mammals twth a small or no allantois (a) it mat expand to obliterate almost coTnpleta> the extra emhT>oroc coeloro the mesodetin coveting the ammon fusme nith that of the chorion, (3) »t ma\ become surrounded b% the allantois thus becoming x asculanzed as in Artiodactyh Pmssodactyla ind Cami^^ra These dificrcnt conditions of the amnion are more hheU dependent upon the degree of development of the allantois than on mtnnsjc functional difTcrcnces in the ammon itself

There ma> be some correlation between the t>pe of ammon formation m mammals and the time and the method of implantation of the blastocvst Early implantation seems to favour ammon formation by cavitation, late implantation is associated with ammon formation by folding


In the development of reptiles, birds and monotremes all of which have mcgalcciihal eggs the first foetal membrane to appear is |he yolk sac It vs formt d vmtiaUy by the extension of blastodermic endoderro round the >olk mass Later the roesodetm becomes interposed between this endodetm and the overlying ectoderm \Nhcn the extra embryonvc coelom appears U splits the mesoderm into an outer somatopleunc layer and an inner splanchno pleunc layer ^Flg 423) The former tot ether with the ectoderm constitutes the Jema or ehrn It while the inner splanchnopkuric layer and the endoderm form the definitive yolk


Metatheria (Marsuptalta) Jnspite of the iact that these mammals have miolecithal eggs they develop a yolk sac soon aficr the falastula stae-e In us fundamental structure this sac resembles very closely that found m the reptiles birds and monotremes After the formation of the endoderm (page 389) this embryonic layer by its own growth extends gradually round the inner surface of the ucutammac ectoderm Eventually the endoderm iQtms a complete lining for the blastocyst wall vvhich thus becomes bilanumr Hill (rgio) from hw study of the development of £)as>unu concluded that the marsupial bilammar blaslo cyst consists of embryonal and extra cmbrvonal

Ftc 424 — Otagrami comparing th^ stager ik early development of a primiUve rod nt of the sijuirrel family [CilrUuj /rtdnmhnealtis) with riniiUr stages in a specialized rodent (laboratory mouse) A B and C — C trtdtCimlintatus (after

Mossman and Weiifeldi 1939) D E and F

Ifw rear a?tir (from Snell 1941)

leyona The fermer is constituted b\ an outer lajer of embf>onic ectoderm tvith an underlying poitionotendodenn (seiiig 40^) these tno lajm ntll form the future embryo The ectra ewhrytinal region separated from the other area by a junctional line is formed bs the Kophohlastic ectodenn (Iroph ectodenn) together nilh the underlying portion of endoderm The tuo layers ectodermal and endodermal of the cetra embryonal region constitute a buatnmar omphalopleurc (or yolh sac) Later In eleielopmetit e-ctension of mesoderm beyond the margin of the embryonal area forms a tnhinunar omphalopicure Since tins mesodermal extension does not usually reach more than a third of the distance to the abembryonic pole of the b asiocyst the b.lammar omphalopleurc preatsts in the abembryomc hemisphere thromhout gestatton and the endoderm of the yolk sac in marsuptals remains ,n permanent contact yyoth the outer nail of the chonomc sac oter a considerable part of m extent (see II, nn 1923 and

^^ove, th,

tije v^T ^ Pericarw ^ ^espiraf dev^, ’ -fJence an ^ f exch^n ^

£S~ ~S- '$?&rs*sz*«Ss^

5f^;S?‘33s '5:5.-S£= t aZ »?5H

an ^'"^mense^ f'^ncZ^- '^^us ,n /r envl^^'T'"^

a storage

a^iantojs varilc “^^ae dur,n 1”^^ indeed, in

appearance and


m the s.ze of endodcrmal component It is iE%a'5 a highW vascular structure -md from us mesoderm is derived the foetal blood svstem to the mam placenta (Figs and 43BI The fused aJhncoic mesoderm (with us vessels) and the chonon Vvsilh us trophoblast) « the foetal portion of all definitive (or chom aUanlou) placentae in mammals The cmlodcrmal portion of the allantois is nell developed in primitive tvpcs (Fig 42B) while in the more specialized species U ma> be either excccdingl) large (Figs 427 and 428) or more often \cr> much reduced (mart) or absent as in some rodents (Ca la)


\s has been stated earlier certam viviparous fishes have developed a t>pe of >olk sac placenta In the amniotes placental mechanisms are found in a slight!) developed condition in certain reptiles and marsupials In the emhcnari mammals placentae are univ ersall) present though as Will be indicated later there is a veo consider able range of variation shown in their nngin histological structure and superficial appearance

Reptilia A few reptiles eg, ccriam snaves, and lizards imfaia and I i/>efO fceno)

arc ovoviviparous that is to sa) the eggs although esscntiall) like those of oviparous forms are heW in the female leproduetive tract until the) hatch The foetal membranes of these species ate not din’erent from those species who c eggs develop outside the bod) Ihere are however a still smaller number of U/ards which are truls vivt parous that is their eg^s have poorl) developed shell and albumen W)ers and their membranes form a rather close union for respirator) and nutritive purposes with the uterine lining of the mother Usuall) it is the )Cilk sic and thr inUf venmg chonon vshich form this placental contact with the maierna.1 tissue but vn one or tv\o species the allantois and the intervening chonon acmallv fuse with tlie uterine lining to form a fairly complex chorjo allantoic placenta (Wcekes 1930 and >935)

Placentatson in Marsupials Like the viviparous lizards the membranes of these lower mammals vary m the degree lo which the )oIk sac and allantois are developed as nutritive, respiratory and excrctor) organs Those with shorter gestation periods like the opossum {Didelphys) and kangaroo {\factopus) seem to depend chiefly upon the )olk sac for nutnijonal relations with the uterus although m all types which have been studied the allantois 1 at least of respiratory significance As has been explained earlier (page 393} the wall of the embryonic vesicle m the opossum eventually shows three different regent '/) an abcmbryonic non vascular portion (hilaminar yolk sac or omphalopleure) (2} a broad vascular zone formed where the mesoderm of the yolk sac remains in contact with the somatopleurc (trilaminar omphalopleure) and (3) the non vascular serosa or chorion Of these three regions though some fluids and substances from the uterine cavity may pass through the first and the third it is the tnfaminar omphalopleure which constitutes the important orpan of nutrition and respiration It can be regarded as constituting a chorjo Mtellme placenta Those marsupials with longer gestaUon periods like Perameles (the bandicoot)

fv - ^ vh- '/%. /5

Fio 425 — Trans\erse sreuon of the aniiin«c>meirial porlion of the uterine cavity m the goJden hamster C 1 e ut aurafus vo jhjw earb atlachment of the blastocMC <30 LRe potlufdfrom Phyiiology ofReprcxluction hy perinisiitn of Messrs Longmans Green 6 . Co Ltd '


have a chorio-allantoic placenta of about the same complexity as the most highly specialized placenta of lizards. (For details of marsupial placentation see Hill and Fraser, 1925, Flynn, 1923 and 1930, Pearson, 1949.)

Implantation in Eutherian Mammals. Before placentation in this sub-order can be described, it is necessary briefly to refer to implantation. In some eutherian mammals S ) P^S) sheep, cow, horse, dog, cat) the chorionic sac remains in the uterine lumen where it expands to fill the greater part of the cavity (Fig 427). This is called central, or circumferential and superficial, implantation. In other eutherian mammals (e.g , mouse, rat, hamster) the blastocyst comes to he in a recess of the uterine cavity which becomes closed off from the remainder of the cavity and in which the blastocyst becomes implanted (Figs. 425 and 426) This is eccentric implantation which later becomes partly interstitial. In still other euthenan mammals (e g , man,

chimpanzee, certain bats) the blastocyst comes to • he in a sub-epithelial position within the decidua

427)* This IS complete interstitial implantation usually occurs at a much earlier stage in development of the embryo than either eccentric or superficial The site of implantation of a blastouterus shows species differences. In many animals (e.g., most rodents and msectivora) on the antimesometrial side of the uterus, in ^ bat, and in Tarsius) li IS on the mesometrial side. In a few species the f implantation is orthomesometrial or lateral, that is,

approximately half-way betw'een the mesometrial antimesometrial positions. This occurs m the

> tenrecs [Centetes and Hemicentetes) where the sites ol

implantation of a litter tend to alternate, every other embryo implanting on the same side (Goetz, igs?)*

Placentation in Bnthetian Man.mals. Part of the explanation of the differences the eutherian placenta lies in the extreme variability of the foetal membranes themse ves, and in the manner and extent of their ^eve op ment. In general, the more primitive groups a membranef more nearly like those of the reptiles. Fig 426 — Transverse section through complete while the higher forms have much more specia ize

uterine cavity of the golden hamster, Cncetus membranes This is true for the developmeniai

r history of the membranes as f ^on

of Reproduction,” by permission of Messrs mature condition Since membrane Longmans Green & Co , Ltd ) have evolved independently in each group

after it began to diverge from the

mammalian stock, orders such as the Insectivora and Rodentia show a wide range m mem morpholog)' entirely within the group Because of this the resemblance between the mem of the primitive members of two orders is greater than that between the more specialize is clear, how ever, that there has been much less variation in the structure of the foetal ^

than in the adult morphology of the various groups For example, it would be \ ’-^ee

for an expert on placental morphology, to distinguish between the membranes of a c *'^P gorilla and man, or betw^een those of a sheep and a goat. In fact, even those o a sea-lion (both Carnivora, but of very different body structure) are very similar. .jy

such as these it can be argued that the characters of foetal membranes have changed m evolution than have the adult body chaiacters and that, there.ore, in general, they are

39 ?


criteria for determining phNlogenetic rdationsbips joammals— particularly affinities between the larger groups such as orders and families , , , v

It w not practicable here to give a detailed account of the great v arietv of methods whereby the foetal membranes of evttheriarv mammals dctclop or even to describe their mature structure Reference to Figs 427 and 428 tvhich illusiratt ihc development of the membranes in the pig dog Tarsius rhesus monkey ground squirrel hedgehog and man eives a general idea of repre senutive types of membranes and placentae These figures should be compared with Figs f2q and 430, and Table ^ to correlate the finer structure of the placentae

The chorion is relatively larpc m relation to the embryo m early stages of development but at term m all < utherian mammals the chononic cavity is practically filled by the amnion which in turn has its cavity ocrupted nevrly completely by the foetus In general the earlv chorion is relatively extensiv e m those forms (pig sheep) which develop thm or scattered areas of placentation at a rather late stage whereas in those which rapidly develop a thick and concentrated placental area (man r^ents) it is relatively small from the beginning A large allantoic vesicle is always a concomitant of a large chorion and of a thin or scattered placental «r“a like that of the pig and sheep


The \a cnUrization of the interposed mesodenw vn the trilaminar omphalopleure of many carnivores rodents and msectivores may give rise to a temporary rhono vitelline placentation (Figs 427 and 428) similar to that found mr’awupiah This serves the important function of ciQurtvIuni the embryo until the somewhat tardilv developing allantois has time to reach and v'vseulariitt the chonon

An entirely dilTerent type of volk sac placentation both structurally and physjologicallv develops m the mammals which show some /brm and degree of so called inversion of germ layer or entypy This is called inverted yolk sac placentation and occurs m Rodentva Lagomorpha (rabbits) many Nlicrochitoptcra (bats) andlnvectivora.andmthe Dasypodidae (armadillos) As de enbed on page 394 and illustrated in Figs fj?? and 498 no mesoderm develops m the abembryonic hemisphere of the blasiocvst or bdammar omphalopleure which therefore remains a very thin, membrane m contact with the uterine w all may disappear com pletcly ormavevennever develop asm the guinea pig In any case the embryonic hemisphere of the volk sac is very vascular and inverts into the abembrvonJc area thus bringing us lining rndodeiTn mio very dose relation to the utenne mucosa over a mde area The relative extent nf this inverted volk sac increases as gestation progresses, and m RodenUa and LagomorpfiQ at term it iv attached almost directly on all sides to (he placenta often in a ring very close to the attachment of the umbilical cord In most sprcics part or aF of (he outer or endodermal surface of the inverted volk sac is covered with well formed and often elaborately branched vascular vilU which are in intimate contact with the utenne mucosa These vilh arc usually longest near the chono allantoic placenta and in roam species they fit into crypts m the foetal surface of the placenta In some rodents (eg, Jamtus) endodermal vilh of the inverted yolk sac become so intermingled wuh the true (chono allantoic) placenta thit they form an integral part of it Its elaborate specialuation and the fact that it persists in a functional condition till term indicate that the inverted volk sac placcma « undoubtedly of great physiological significance and a major factor to be corjvjdered m laboratorv experiments concerning placental function m the*e animals

CHORIO ALLANTOIC PLACENTATION IN EUTHERIAN MAMMALS ^^am^lahan placentation may be defined as an apposition or fusion of the foetal membranes ^ the uterine mucosa (o permit of phvstolo^cal exchange between the foetus and the mother I he most tspical of the structures ind the defimtivc one m all Fmhcna is the chono allantoic

placenta However other placental mechanisms exist dunng the development of each euihenan

mammal Of these the chono vilelline and inverted yolk sac placentae of .ome tvpes have





been described above. Other accessor)'^ placental adaptations are illustrated and explained in Figs. 427 and 428. Further discussion of eutherian placentation here is confined to the chorioallantoic type The variety of gross forms of chorio-allantoic placentae has excited interest out of all proportion to its significance. Fig. 430 give some idea of the appearance of the better known varieties

A summary of the finer structure of the main types of chorio-allantoic placentae is given m Table V This is based on Grosser’s (iQsy) classification of them according to the intimacy of the union between the foetal and maternal tissues, or in other words, according to the structure of the membranes separating the maternal and foetal blood in the functional parts of the placenta Grosser rightly maintained that this “placental membrane” is the structure of greatest physiological significance in any form of placentation. The terms which he applied appear S'jrnewhat complicated at first sight, but will be seen to be appropriate, being lormed



Type oj ‘ c 1

1 Epitkeliochonal




Maternal ti,su

Endotlie >


Epithelii 'j

Foetal tissue

+ :


'h 1


Endothei' ,

+ 1



Familiar exari- \

Horse, pig, cattle

Cat, dog

Man, monkey.

Rabbit, guinea pig, rat

Main zoological t'l '1




\niodactyla, Penssodactyla, Cetacea, f Manidae,

1 Leniuroidea, American mole.




European mole





Most Microchiroptera, Hyracoidea, Myrmecophagidae, Dasypodidae,

Most Insectivora, Lower Rodentia (Sciundae, Myomorpha)

Higher Rodentia (Leporidae, Geomoidea, Hystricomorpha)

by a combination of the names of the maternal and foetal tissues which are in contact (Fig 4 ^ 9 ) For instance, if, as m the pig, the epithelium of the utei us persists and the trophoblast 0 t chorion meiely lies m contact with it, the placenta is spoken of as “epithelio-chortal ^

uterine epithelium disappears and the chorion comes into contact with the endothe mm the maternal vessels, as in the dog and other Carmvora, it is an “endothelto-chorial type considered that in many Ungulata the epithelium disappears leaving the chorion m mi with the connective tissue of the uterus. To this ty^ie he gave the name “syndesmo-chort^^^^ Since this condition occurs only in a very limited area of the bovine placenta, an is probably atrophic and non-functional, this type of placentation has been omitte ro table. There are accessory placental areas in other species which structurally syndesmo-chorial conditions, but there are no known cases where the main chorio p placentation is of this t^e. In many mammals (e g., Rodentia, most Insectivora, -yora,

and Cheiroptera) the invasive activity of the placental trophoblast is greater than in so that eventually even the endothelium of the maternal blood vessels is destroyed endothelio-chonal placenta becomes “ haemochorial” While Grosser’s classification ^00

considerable value in the study of different types of placentation, it cannot e app rigidly. Detailed study of the placentae of a number of species has shown


rc^ ate nceexari m an anrmpi in place a Riarn platrma m one nr rllicr nfCttmtei i calcROtaea In manv Lnculaica ftt raample it ba. I>«n .bnnn ibal cap.Uanra ate fnumi in the iropliolilasl ... i

In connwtion >mUj pliccnial iinicturr it mmt Mi • !*■ rrTnpml>rroi ifnt inan\ cliorioMhntoic placcntir Ini e a th.cVrr pberntM infmbrmt m Minr f -iThrr jnqri than \i\cT Hmi m thp rahhit iihrn tlir athntmc circubiinn i» fint rital.hihn! tlirrc arc arraiishcrr llic trophni>bix of thf ciiorion » ju't vntU the ulcnnc cptllicimm an cpithrlirv-clinnal rondition

baler in tlm animal a Incmnchonal cnmliu.m it trachctl tthcrc the maternal hWl it m direct contact ttilh thr irnphrhhti Slill liter the tn>phn»>bit itvlf »rrmt to dioppear from much

Hsrrnwfei 9I Ubff

int«cti<eri (CKCpt H«1eil Ch fOpt«ri HjrriM tfei T»f to tfea and lower S <id«tt Rodentii

Dupl c dent «nd H (her S m pi cident Podtmla

Oeifpodo iei Ctftop e^e<o 4*t and Hoffiineidci are « Hoot Cefeo del New World Am eaten and Oertvioptera an (rabeeular

[ Cp iref o><^eool(An oduifla (S odea Cawitlodra Traxviodei) PeruodaetpU Cctacta Lemgrt New World Holet and 0*d World Am-etten)

tnd t*^l (Carnirorti SloiKt Old World Holei and S ten a)

e £p iNrl oKhonol (hjrpoihetlcal)

MORPHOLOGICAL TYPES OF CHORIO ALLANTOIC PLACENTATtON Atfinjed at 1 tree with ibe mott pilmrtWe tjrpe Lrtow T»ie ijnatl V»p ffurra ibow In 1 mpt fed form (he iiructurc «( (he placental membrane aeparat nj the maternal and foeui blood « A ' t 4^ m T pK«»l < «BW U .« f P •> I w 9 Iwl IV ■ Ql M I Vhi>I >a flooe

Iin Itkwe m* IM mS •« 4t>rc.e

1 10 ^29 — I)i3((raini illuit rating it e riain morpl t4oC‘c»l t>1‘n of cliorio-aUantoic placrnta

of the placenta so that onl) foetal endnihrliiiin separatee tJic luf> 1 ;Io<k 1 streams a hafmo tndotktUal condiuon (Motsman 1936 ) The frrvdom uith tthich sidattances pats from one blood stream 10 the other is correlated to some drv^rec \Mth the thieVness ami slruclure of the placental membrane Thick membranes are pmbab]> lot [lermeablc than thm ^tso the earlier thicker placental membranes of a Riven ipecics arc stated to l>e less permeable than m the later tlnnnrr stiRcs (I lexner tnd Gcihorn tgp see alto pai,c BO It should be stated houcser that estimations of placental permeabiht) on the apparent structure of the placental metnliranc ate still leniativc

A placenta n said to be non deciduous if there « no actual fusion of foetal cliorion to the uterine tissues thus at hirth these pheenne separate without teanne; maternal tissues and therefore without Joss of blood by the mother All epithclio-chnnal tlilTute and rotjlcdonart



placentae are of Jis variety In all other types fusion takes place and more or less maternal Hssue IS shed and maternal blood lost, at b.rth; hence these are deciduous. SpecSclcX cells, as found m human and many other uten, are often absent from decdLs pWentaf

eg., tn the dog placenta, which is considered deciduous only because the maternal da„£ tissues and blood vessels are torn at birth Sianauiar

an ” cp«heho-choriaI placentae are vdlous (Figs. 427, 428 and 420)

All endotheho-chonal, haemo-endothehal and most haemochorial types f re UnLue (Figs 42 ' 428, 429 and 43. A) Some haemochorial types, especially among the primates, exhibit Lin intcr-gradations between a labyrinthine and a villous structure (Fig 43.) Applrentlymanand

ZoRiLLA Brown Bear

of the placema^.^ie^i!^ chorionic sacs of a number of mammals to show the gross forms

zonarj’ or annular rar deer and cow, cotyledonary; monkey, btdiscoidal, dog, etc,

derivations of thr zonary, otter, polecat, ZoriUa and brown bear show special

carnivore zonary placenta

Fiff. 68 illu^rateiffb^ ^^present the maximum expression of the haemochorial villous condition, labyrinthine placenm”^^^if*^ of development of one of the more primitive types of haemochorial Ume seems to be b ' J j change over from the labyrinthine to the haemochorial villous rcsultins- first in a t coalescence of the trophoblastic tubules carrying maternal blood,

that in most labvrmfb'^^^ ^ definite villous condition. As a general rule it seems

directions in areas d I^acentae the maternal and the foetal blood streams flow in opposite UqsSl has desrribpVfi^^ ^ j enough to have functional interchange. Mossman

and there is a nnss.ivi ^ P|^y®*o^ogical advantage of this arrangement in the rabbit placenta placenta (Chapter V Ind a somewhat similar functional provision exists m the human



One of the most puzzling problems of comparatisc morphogenesis of the foetal membranes has been raised h) the demonstration of the peculiar mesench>-niatous ewa embr)onic tissue in the earl> embryos of the primates generally (Hill 1932) of the lemurs (Gerard, i93'>) of man (Streeter 1926 and Hertig and Rock, 1941) and of the monke> (Heuscr and Streeter, 1941) and Its relation to the exocoelom and 4 oik sac From a stud> of comparative embryologv it would be expected that this mesoderm would be formed bj proliferation from the posterior (later pnmitne streak) region of the embrjo whence its cells would spread into the extra embryonic regions However, in both monkev and man the primary extra embryonic mesoderm develops before the appearance of the primitive streak (Figs 59 60 and 432) Hill (1932) and Florian (1933) are of the opinion that this mesoderm arises from the immotic ectoderm postenor to the site of the future tloacal membrane, Gerard (1932) believes that it arises from the endoderm of the volicsac Hertig (1935) Wislocki and Strcctei (1938) and Heuscr and Streeter (1941) have investigated the origin of this mesoderm in well fixed material from the monke> and are com meed that this pnmarv mesoderm IS derived at least in part, directl) from the tropho blavt Hertig and Rock (1941) found evidence of the same condition in their 8th-i2th da> human cmbr>os

— A sect on of a 12 day macac^u? blastocyst i^e yolk sac has now made us appearance between ihe mesoderm and the embryonic ectoderm I Vter Heuser and Stteettr 1941 ) x c 310 'Reproduced by the courtesy of the Carnegie Institution of Washinftol )

Fic 431 — Sections through the placenta of the New World monkey C/irysathn* m Kiialut \ labvnnihine portion E villous portion (After Hill 1932 }

Streeter and Hertig and Rock den> homolo gjcs between the earlv tissues and structure of the primates and those of other mammals and regard the precociousl> developed mesoderm and the cavnties in relation to it as special adaptations found only in higher primates If, however one recogmzes the value of comparative studies, as Heuser working upon the same matenal has done then an early primitive bilammar yolk sac can be recog mzed in the human and monkey with many resemblances to that of other mammals The recent work on the macaque has shown that the primary yolk sac which is essentially like that of all other mammals does not give nse directly to the secondary yolk sac The latter seems to arise by a rearrangement of

human embryology


the originally flat plate of disc endoderm to produce, adjacent to the embryo proper, a separate small cavity which qvnehly becomes surrounded by haematopoietic mesoderm The cavity of this secondary yolk sac seems to have no continuity with that of the pnmary sac (Fig 432) and as it enlarges the cavity of the latter recedes towards the vegetal or abembryomc hemisphere In man as has b«n described in Chapter V, the abcmbry'onic part of the pnmary yolk sac becomes separated completely from the remainder A surpns ingly comparable process is exhibited by the sloth Bradypus grisfus (Heuser and islocki, 1935), ^^here the exococlom extends around all except the abembryomc end of the primary yolk sac where the latter s original connexion with the trophoblasl is maintained A constriction develops between the abembryomc and embryonic portions of the sac which results in complete separation of the two portions There is then a small proximal haematopoietic, splanchno pleunc yolk sac homologous with the definitive yolk sac of man and the macaque, and a distal or abembryomc degenerating portion of the primary sac comparable with that part of the pnmary yolk sac of the monkey which is relegated to the abembryomc hemisphere of the chorionic vesicle It seems reasonable to assume therefore that the relatively direct and early method of separation of the two parts of the yolk sac m the macaque is merely an abbreviated and specialized method of pinching off of the distal portion seen m its more pnmitivc form in the sloth and possibly in man where the primitive abembryomc portion of the yolk sac is indicated in some embryos (Chapter V and Figs 75 and 76)


de Beer G R (i94o) Embryos and Ancestors Oxford Unn Press London

Boyd J D and Hamilton W J (igs'*) Cleavage of the egg and implantation In Press— Physiology of Reproduciion (Marshall) Longmans London

Caldwell H (1884) Telegram Monotremes oviparous ovaim meroblaslic Read at British Association Meeting Montreal '•nS Sept 1884 Brit Assoc Rep Montreal Meeting 1884 Cate Hoedemaker N J ten (1933} Beitrage zur Kenntniss der Plazeniaiion bei Haien und Reptilien Der Bau |der reifen Plazenta von Mustrlus hnis Risso und Srps ihalttdet Merr [Chaletda lridael)luj Laur ) ^tilt f u rnikr Anal 18 299-345

Flexner L B and Cellhorn A (t942) A comparative study of placenta permeability using radioactive sodium Anal Rtt 82 411-412

Flynn T T (1023) The yolk sac and allantoic placenta in Prr<i«r/« Quart J Micro Set 67 123-163 — (1930) The uterine cycle of pregnancy and pseudopregnancy as 11 is in the Diprotodont Marsupial Bdieneia runirufus Proe Unn Set Setv Sauth ttabs 50*^531

and Hill J P (1939) The development of the Monotremaia IV Growth of the ovarian ovum maiura

tion fertilization and early cleavage Trans ^eef Sec Lend 24 445-622 — (1942) The later stages of cleavage and the formation of the pnmary germ layers in the Mono tremata Free Z^al Sac Lend AIll 233— >53

— {1947) The development of the moooiremata PariVI The later stages of cleavage and the formation of the primary germ layers Tranj Sec 26 i-tjt Gerard P (1933) Etudes sur I ovogen^se el 1 onir^en^e chez les Lemuriens du genre Co/o 0 Arch de Biol _ « 9o-«5t

Ooetz R H {1937) Studien zur Placentauon der Centetiden II Die implantation und fruhetvtwicklung von HemicenteUs semiiptnosus (Cuvier) ^ f Anat u EntnGesch 107 274-318 ~ — (>938) On the early development of the Tenrecoidea (Hf»Mf*Bfel« jemupinofw) Bxomorbhosu 1 67-79 Grosser O (1927) Fruhentwicklung Eihautbildung und Placentation des Menschen und der Saueeuctc Bergman Munchen ^

Haeckel E (1874) Die Gastraca Theone die Pbylogcnelische Classification des Tierreichs und die Homoloeie der Keimblattcr Jenauehe Znls J'raturw 8 1-55 ®

Hariman C G (1920) Studies m the development of the opossum (Oi*//A>s u ginianu Z. ) W istar Institute Philadelphia

Hertig A T and Rock J (1941) Two human ova of the nre villous stage having an ovulation age of about el^en and tv eUe days respeeiivcly Coning Emh^et Ceamegie Inst Wash 29 i27-i>i6

^ ^ Development of the macaque embryo Contrib Embryol Carnegie

^d VSisl^k, G B (1935) Early dcvelopmem of the sloth (Brarfj-^Hr^rufw) and Its similarity to that of

Mil Gontrib Embryol Carne telnsi Wash 25 1-13 ’

j*’' ® f IJidf/pAys Quart J Micro Set 63 91-140

1,1932) The developmental history of the Pnmates PW Trans Roy Sec Land B221 a-t 1-78 Zeelfo^ Und the female urogenital organs of the Didclphy^dae Proc

vande^Hont C J (1942) Early stages in the embryonic devcVopmeni of Ele/iftantulur

5 Vr J Med Set



Hubrecht, A \V (i8go) Development of the germinal layers of Sorex vulgaris Quart J Micro Sci , 31 , 499-362

(1908) Early ontogenetic phenomena m mammals and their bearing on our interpretation of the

phylogeny of the vertebrates Quart J Micro Sci,^ 3 , 1-181 Jacobson, W (1938) The early development of the avian embryo I Endoderm formation II Mesoderm formation and the distribution of presumptive embryonic material J Morph , 62 , 415-443 and

Kcibel F (1889) Zur Entivicklungsgeschichte der Chorda bei Saugern (Meerschivemchen und Kanmchen). Arch Anat Physiol , Anatom Aht , 329-388

Kerr, T (1934)- Notes on the development of the germ layers in diprotodont marsupials Quart J Micro

Sci,n, 305-315

Lehman F E (1945) Emfuhrung m die physiologische Embryologie Basel McCrad), E, Jnr (1938) The embryology of the opossum Amer Anat, Mem, No 16

(1944) The evolution and significance of the germ layers J Tenn Acad , Set , 19 , 240-251

Mossman, H VV (1926) The rabbit placenta and the problem of placental transmission Am J Anal,

37 , 433-497 ^ ,

(* 937 ) Comparative morphogenesis of the foetal membranes and accessory uterine structures Contrib

Embryol , Carnegie Inst Wash , 26 , 129-246

and Weisfeldt, L A (1939) The foetal membranes of a primitive rodent, the 13-striped ground squirrel

"im J Anal, 64 , 59-109

\ I Lon, P L V 1 940) The foetal membranes of the kangaroo rat, Dipodomys, with a consideration of the phylogen)

of lie Geomyoidea Anat Rec , 77 , 103-127

P.t‘tefia J .1937 fitude sur la gastrulation des vertebres meroblastiques II Reptiles Arch Biol, Pans, 48 105-184

(1940 I n aper^u comparatif de la gastrulation chez les chordes Biol Rev, 15 , 59-106

(1940 On the formation of the primary entoderm of the duck [Anas domesltca) and on the significance

ui tin Ijj'jr/inar embryo in birds Anat Rec, 93 , 5-14 Patti. rson J 1 ’Mjg') Gastrulation m the pigeon’s egg — a morphological and experimental study J Morph,

20 ti I ;

Pearson J o oo Placentation of the marsupialia Proc Linn Soc Lond , 161 , 1-9 Prttr K 10 ’p Die erste Entwicklung des Chamaeleons, verghchen mit der Eidechse Z, f I”* Ot 0 103 , 147-188

(■933) ■‘ 3 ic )' rere Entwicklung des Chamaeleonkeimes nach der Furchung bis zum Durchbruch des

Lrdarms [[ / Anat u EntwGesch , 104 , 1-60 , .

Rabl C ^1915 r Jouard van Beneden und der gegenwartige Stand der wichtigsten von ihm behandelten Probleme Arih Mikr Anal , 88 , 1-470

Snell, G D (igii) Biology of the laboratory mouse Blakiston Co, Philadelphia .

Streeter G L 11926' The “Miller” ovum — the youngest normal human embryo thus far known Conlrt Embryol , Carnegie Inst Wash, 18 , 31-48 ^

Turner, C L 11940) Pericardial sac, trophotaeniae and alimentary tract m embryos of goodeid fishes J H/or/y/i , 67 , 271-289 c

Vogt tv (1925) Gestaltungsanalyse am Amphibienkeim mit ortlicher Vitalfarbung Rom’s Arch, 1 542-610

(1929) Gestaltungsanalyse am Amphibienkeim mit ortlicher Vitalfarbung Gastrulation und eso i.c dermlnldung beim Urodelen und Anuren Arch Entwmech Org , 120 , 384-706 ^

Weekes, H C (1930) On placentation m reptiles II Proc Linn Soc New South Wales, 55 , 55 ^- 57 .

(1935) review of placentation among reptiles with particular regard to the function and eio of the placenta Proc Zool Soc Lond , 625-646


Presumed I Dimensions of Dimensions of

Author and a?e m blastocvsl embryonic mass

embryo ‘^*1* (in mm) (in mm )

Reference to publication

STAGZ i — Tht Eatlj Blastotysl Stage up M the appeaiante oj the talk

Heuser and Streeter

«94» ,


0 f87Xo 166 1

' 0 108x0 to8


(approx )

(approx )

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0 12x0 306x033

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■ 94


0I2 jX 03X045

0 o8j X 0 o8j

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(Cam no 7699} 1


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I f«f 31

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I Trans Rot ioe I Edin 61

1 CoHr £m6 Cam

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Hubrecht, A W (1890) Development of the germinal layers of Sorex vulgaru Quart J Micro Set, 31 , 499-562

(1908) Early ontogenetic phenomena in mammals and their bearing on our interpretation of the

phylogeny of the vertebrates Quart J Micro Set, 53 , 1-181 Jacobson, \V (1938) The early development of the avian embryo I Endoderm formation II. Mesoderm formation and the distribution of presumptive embryonic material J Morph, 62 , 415-443 and


Kcibel, F (1889) Zur Entwicklungsgeschichte der Chorda bei Saugern (Meerschweinchen und Kaninchen) Arch Anat Physiol , Anatom Abt , 329-388

Kerr, T (1934) Notes on the development of the germ layers in diprotodont marsupials Qjiart J Micro Sci , 77 , 305-315

Lehman, F E (1945) Einfuhrung in die physiologische Embryologie Basel McCrady, E, Jnr (1938) The embryology of the opossum Amer Anat, Mem, No 16

(1944) The evolution and significance of the germ layers J Tenn Acad , Set , 19 , 240-251

Mossman, H W (1926) The rabbit placenta and the problem of placental transmission Am J Anat, 37 , 433-497

(1937) Comparative morphogenesis of the foetal membranes and accessory uterine structures Contrib

Embryol , Carnegie Inst Wash , 26 , 1 29-246

and \Vcisfeldt, L A (1939) The foetal membranes of a primitive rodent, the 13-striped ground squirrel

Am J Anat, 64 , 59-109

N If Ison, P E (1940) Thefoetalmembranesofthekangaroorat, Di/iof/omyr, withaconsiderationofthephylogeny

of the Geomyoidea Anat Rec , 77 , 103-127

Pacteels, J 11937' fitude sur la gastrulation des vertebras meroblastiques II Reptiles Arch Biol., Pans, 48 105-184

(1940^ Un aper9u comparatif de la gastrulation chez les chordes Biol Rev, 15 , 59-106

(^ 94 j/ F)n the formation of the primary entoderm of the duck (Anas domestica) and on the significance

of the bilarninar embryo in birds Anat Rec, 93 , 5-14 Patterson J T '1909) Gastrulation in the pigeon’s egg — a morphological and experimental study J Morph,

20, 65-1. r

Pearson J .1049 Placentation of the marsupiaha Proc Linn Soc Land, 161 , 1-9 Peter K Jiqf, 5' Die erste Entwicklung des Ghamaeleons, verglichen mit der Eidechse Z f EntujGescr 103 , 147-188

{’935) riere Entwicklung des Chamaeleonkeimes nach der Furchung bis zum Durchbruch des

Urdarms ^ f Anat u EntwGesch , 104 , i-6o

Rabl C (1915 (iJouard van Beneden und der gegenwartige Stand der wichtigsten von ihm behandelten Problemc Arch Mikr Anat , 88, 1-470

Snell, G D (1941) Biology of the laboratory mouse Blakiston Co, Philadelphia Strectei. G L (1926) The “Miller” ovum — the youngest normal human embryo thus far known Contrw Embiyol , Carnegie Inst Wash , 18 , 31-48

Turner, C L ("1940) Pericardial sac, trophotaeniae and alimentary tract m embryos of goodeid fishes j Morph 67 , 271-289

Vogt, ^V (19251 Gestaltungsanalyse am Amphibienkeim mit orthcher Vitalfarbung Roux’s Arch, 10 j 542-610

(*929) Gestaltungsanalyse am Amphibienkeim mit orthcher Vitalfarbung Gastrulation und Mesodcrmlnldung bcim Urodelen und Anuren Arch Entwmech Org , 120 , 384-706 Wcekes, D C (1930) On placentation in reptiles II Proc Linn Soc New South Wales, 55 , 550-57 (’ 935 / A review of placentation among reptiles with particular regard to the function and evo u of the placenta Proc Z^ol Soc Land , 625—646


I rnutned

Dim mioni of

Dimensions of

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1 laslocMl

embnomc mats

cmbr> 0

Due da\-»

(in mm )

(m mm )

Uefctfnce to j ublication

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0 iijV03xii4a


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0 3.,l XO 404 XO 421

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I the Protest 0/ formalist but the Primiti e

1*6x0048x0116 Conir Fmb Cam

Inst 31

o'-tXiOj JffA f Cjtnak 102

118x0*4X004 ' Leip t u Mfin Arch

I / Crna* 124

D2IXd*i6 ! Cont Emb Cart I Inst 29





Dimensions of

Dimensions of

Author and

age m

chorionic vesicle

embryonic mass

Reference to




(in mm )

(in mm.)


STAGE 4 — The Ammoltc and Talk Sac Vesicles Enlarge Funher, the Villi Branch, the Embryonic Disc becomes Oval, the Primitive Streak and Knot and, in the later part of the Stage, the Cloacal Membrane appear

Heuser, Rock and Hertig


i 3 i


0 04X0 22 XO 253

Contr Emb , Cam Inst , 31

(Cam no 7801)

J Anat Lond , 83

Morton (Biggart)



2 53x2 10 XI 68

0 27x0 027x0 16

Brewer (EdwardsJones-Brewei)



. 1938


I 85 X I 71 X I 01

0 209 XO 177

Am J Anat, 61 Contr Emb , Cam Inst , 27

von Mollendorff




I 5 X I 15 X I 0


Zeits f Anat u Ent ,


Scblagenhaufer and



20X1 6x1 0

0 24x0 28 XO 04

Arch f Gynak, 105


Anat Anz , 37

Zeits f Mil Anat,


Fetzer "1

Fetzer and Floiiin 1





I 56 X I 048

0 26 XO 215

von Mollendorff (WO )

i 1925


j !

2 52 X 2 16 X 2 06

0 25 XO 22

Zeds f Anat u Ent , 76

Teacher J

^ TB II Bryce J

1 1924



28x26x2 25

0 2 X 01

J Obst Gyn Brit Emp , 31

Trans Roy Soc , Edin , 53


' 1908


25X22X1 0

0 25

Karger, Berlin

Wilson (Rochester)

i 1945





Contr Emb , Cam Inst , 31

Strahl and Benecke \ Flonan and Benecke J

j 1910

ii 930 -i




! Bergmann, Wiesbaden Anat Anz Erg , 71


1 1932



0 23 XO 3 XO 06

J Obst Brd Emp ,39

Flonan (Bi 1)



2 13 X 2 12 X 2 13

0 35x0 34

Anat Anz Erg, 63

von Spec (von H )



4 0

0 37x0 23

Arch f Anat u Phys

STAGE 5 Heuser, RocL and Hertig

(Cam No 7802) Meyer

Johnson (HR i) Jones and Brewer

Stieve (Hugo)

Flonan (Bi 24) Flonan and Hill (Manchester) Thompson and Brash Streeter (Mateer)

Gladstone and Hamilton (Shaw) Grosser (\Va 17)

Hill and Flonan (Dobbin)

Rossenbeck (PehlHochstetter) Grosser (K 1 13) Heuser

(Cam. no 5960) George


The Primitive Streak Elongates, the Notochordal {Head) Process and Archenteric Canal develop, and the Villi become branched

.. ft I I — I Jf mf



2 2 X 2 35 X 3 75

0 35 X 0 05 X 0 42



26x2 1x2 72

0 41 XO 4


i 5 i(’)

0 55 X 0 43



60x50x25 (before fixation)

0 58 X 0 782



44x47x3 8

0 57 X 0 63


3 05X3 036x3 029

0 62 XO 41



4 28x3 28

0 87 XO 625



10 0x75X40





0 92 X 0 78

' 94 '



I 05




0*98x0 7


16 (2)


0 96x0 59




I 77 X I 02

i 1913


8 0X6 0

0 83 X 0 50



15 0 X 14 0X9 0 (external)

I 53X0 75

i >942



I 01 XO 83

1 >918



2 00x0 75

Contr Emb , Corn Inst , 31

Arch f Gynak , 122 J Anat , 75 Contr Emb , Cam Inst ,29

Zeds f Mik Anat,

7 ,4

Bralisl lekar " J Anat Land , d 9 .

7 Anat Land , 58 Contr Emb, Corn Inst ,9

J Anat Lond, 7 b.

Zeds f “

Ent , 94 .

Phil- Trans RoySoc , B 219 Zeus f Aoat u Ent , 68 Anat 7 /r >.47 Contr Emb , Cam Inst , 23

Contr, Emb , Cam Inst ,30

Contr Emb , Cam




' DimelMions of

Dimemiont of


Author and

a(*e in

1 chononic \mcle

embryonic man

Reference to




i (in mm )

(in mm )


STACE G . flu \eliKhardil Plali breemts nHtnolaltd in llu Roef

of llu Jolk Sae iht

NfuvnfrrK Ca'ial

U Prisinl

tht Srur<i{ Platt oitd faUt enJ the Eaih

Rfftegul bfgit li drttlaft



ifl-i9 j

54x3a 1

1 17x06

1 Ireh f \ltk Inal

a Jnl -JO

Bryce (M Int\re>



14 0x13 oxSo

1 4x05

' Ttafu Rtr Sot

^on Spec (Clae)



1 Fdiit 53

19*20 1


‘ 54

^ irch / Inal a


1 Phjt



'hon, 310. 323

‘ A’ disc, 367

Abdomen, muscles of, 359, 363 Abdominal

paraganglia, 329 pregnancy, 69 Abduccns

ner\c, 279, 288, 306, 308 puclfus, 285

\burant ductules of epididymis,

230, 231. 259

■^'1 iniinal development, 125 '’1' >iinalities

cidleientiation, 126

ft' environmental influences,

, 1 246 303

M ^ .1,-s ; 127, 244, 303

u 1 ni o 126, 245

d \ riopni' I 1 of gut, 214

' ' Mu’ u ! lb -,3 1 iSSOi se\ "I 1

ctrtiiunaiv . l \c 'ondroplavi '

\cf JStIt

canghon 3 5 nerve 270 \coustico-i 'Id \crosomi \dcnoidv I'lf)

\dipi ' >1^ f ,1 d \dit V I 1 \dru il gland 320 \drfnalin ^28, 329 Advchcntcv vena. 164 \fTcrtnt

nerve fibres. 283, 306 neurons, 273 Age, 104

determination of, 105 Agenesis, 126, 304 Agglutinins, 129 Ala

orbitalis, 343 temporalis, 343 .Alar lamina, 272, 283, 285 Alimentary system, 176 .Alisphcnoid, 343 Allanto-entcnc diverticulum, 70, 76, 176 vessels, 76

.\llantois, 76, 77, 80, 234, 389, 394 blood vessels of, 158, 394 duct of, 76 function of, 394 in man, 76, 176 .Alveolar phagocjtes, 201 \Kcoli of lung, 198, 200 Amastia, 373 .Ambiguus nucleus, 284 \mbK stoma, ancurogcnic limbs in. 306

.\mcloblasiic layer, 374 .Amcloblasts, 374 .Xmnto-cctodermal junction, 79 .Amniogcncsis, 392 in man, 45

.\mnion, 45, 78, 389, 392


foetal membranes in, 390 placentation in, 395 Amniotic bands, 126 cavity, 45, 70, 78 duct, 79 fluid, 78, 81 v'olume of, 81 Amoebocytes, 97 Ampulla

of semicircular canal (Fig 353), 322

of vas deferens, 241 of Vater, 209 Amylase, 216 Anal

canal, 211, 250 filaments, 390

membrane, 58, 212, 235, 250 pit, 250 sphincter, 360

Anamniota, foetal membranes in, 390 Anastomoses

mtersubcardmal, 166 post-costal, 159 post-transverse, 159 pre-costal, 159 vitello-umbilical, 162 Anencephaly, 303 Aneurogemc limbs, 306 Angioblastic theory, 136 tissue, 136

Animal pole of ovum, 380 Annular artery, 319 Annulus ovahs, 145 Anoestrus, 33 Anomalies

of cardio-vascular system, 1 72 of eye, 317 of face, 1 1 5 of genitalia, 260 of gut, 214 of heart, 1 72 of kidney, 233 of mammary gland, 372 of neural tube, 303 of placenta, 82 of umbilical cord, 83 of urogenital system, 258 of uterus, 243 of veins, 1 72 Anterior

cardinal vein, 139, 164 chamber of eye, 32 r commissure, 301 lobe of hypophysis, 292 nans, 114 nerve roots, 304 Antigens, 129 Antrum, tympanic, 326 Anus, 215, 387 imperforate, 215, 250, 260 Aorta

aoriico-pulmonary septum, 149


coarctation ol, 173 dorsal, 152, 154 branches of, 158 double, 173 ventral, 152 Aortic

arches, 152

persistence of, 173 bodies, 330 sac, 152-154 Aperture, median, 289 Aponeurosis, 368 Appendicular skeleton, 349 Appendix

of epididymis, 241, 259 of testis, 243, 259 v'ermiform, 211 Aqueduct cerebral, 288 of cochlea, 324 Aqueous chamber, 320, 321 Arachnoid, 320 reticulum, 287 Archenteric canal, 49

Archenteron, 384 Arches aortic, 152 branchial, 153, 17S hyoid, 153

mandibular, 109, 153 pharyngeal, log, 153, t?" visceral, 178 Area

opaca, 388 peliucida, 388 Arm

arteries of, 161 development of, no, 349 muscles of, 362 Areolae, secondary, 337


patent ductus, 173 truncus, 149, i 5 ^> *73 Arteno-v’enous shunt, 173

Artery, or Arteries, 152 annular, 319 anomalies, 1 72 aortic arch, 139,

xial, 160 lasilar, I 57 ) *00 irachiai, 162 iranchial arch, i 53 > * 7 ° ironchial, 158 arotid, i 54 ~* 5 ® erebral, 157

ervical, 161

oeliac, 158, 218

ohc, middle, 218

omes nervi ischiadici, ommumcating

lorso-lateral segmental, i59

[ucius caroticus, 150 r»mrvraL xGs


IM)I \

' a{piraiu 312

acfn%. n part ff 3 ij rin{;l n M I t^n)(anum 3>

\uftfiilat »{

Nut rt mir 11 nri « ») t n I Nut rtllr IJI

Nut I

. iR

,nf f r 1^ Ml Ml

. ir--f> f 7 IjH >Mi Ml

an n i 1

j anrfratif •-<{ ! nil Ml

IW, n al 10 (lannc al \il |)r n II im, 1 . il U

j >«t I tarvehiil nl » 1 1 1

lult nan artf 15. ailiat M r tal Mil frnal ISa rriinal 31'> tarral tn Ml Ml fiffn nul tnmai 15 1 iprrtiniif IjI p nal iji •tlanrlni IjR pirn in alapr {ill lai 3 j iiilirlaiian IjC K I urrar nal |j > iilial 1C' ill tnr nical iGi ulnar iCj

uml ilifal r I 1 ij« 

Nfit i ral iCo nifal ijO

iiirllin 77 ijfl 310 Nrt fcial paril ms; nmt 41 Nn-rpijl iiic f Id tgo Nr>tet id carlilatje 3jn lucl^ini;! 190 N c ndinc

Aitroc^ifi aC*"

Aslro<r)toblaili afr Aiynvax a doml 1 31 3 Ntlas (Iig 37i) 3,0 Airnia of gill at5 of on phagH aoj of < varian 1 Hide

bundl 2 ^ 7 canal 140 143 diiiJionof ijf endocardial cuilii 11 141 lal vahes 151

Ntrium of heart 140 143 171 abjoTpiion of veinj inio I4f

Niitel.c Rt wll f l‘ 1 Nio

R irulati n in 3 f Nx al

an n if

1 filam nl f primal / it iVd t n I nl irai lal 33 1



Dan I

, an»n 1 r iM

r lenii n < f cui :

Darn r | la nial f Dan ti rnal 341 Dan! In clan I 3^3 I Daul

I lamina a i »• 3 I ,, 3»»

' Da liar

art r> » U I lam ra llic 3 , 3J3 I Da 1 (>e iumuli Datil t le I lac ! D lamtnxr et> 1 rx


| ca( dlaiiet 3 )

duel “ill

D Iiarv api aratu 1 a D C fte»i» « f 3<

Il nil I f Niet 11 rill

I ci ancm m r.rculaii i> ai

• Irtictl I I

mull pie 13 > 131 W icll I3« 

Iliad 1 r

an tiiiali 1 4 f 31"^ incrn if 34*1 urman 347 I Dla I Ria mrianei I nr 331 IllaiKK irj 41 3na I Dla I <>ii 7 44 Cl 3na I I ilanusiar 70

Slages ( Np|irn lix> 40!! Dla loit r 3H7 ■ 111 m ir ^ 43 Cn 3 I p< irnliaiiiie* of 43 i-*i DIatic poral plat 3UIS Dlaii jifir 4) y 3D1 iipi t 3ni Dlatiufa 7 3U3 Dlomi 99 aoB 235

devfl pmrnt of 99 forinalion iheonrs f 11 saUntix 71 7G pol)ph>lrliC llieor) 103

[.bd""'’ '■

aoriic 330

D- f

carotid 14 cl rt maDm 1J »

' geniculale 3 (I mamillan '*e ) cfpanctra 1 i jineal s' r ?*: I j luiiarx 3 fl - d {«tat III 4 I trxTi iitali ri of 3 tialV I ‘ iifiin nl rant! lal I t

wall rl»iire / 3j /urLrrlan I! • 3 i le If D. nm m

4^ 4


rartdag ti{ cell 33' t mjatl 33^ lerti al 314 141 <i 1 I I Ml ni ol 334 f tl nifi Ij3 er. I <1 n Iral 314 jnifatariilac 11 in 334 snira i er I ran 1334 lacuna 33'

I nc 3J

marn h k i 33* m ml ran 114 13' l--nnt al 31’ jiimary 33j

• loll 340

»I ’’C' 3/

D.t;ella I x.r 34'

raftiiil jt


• tiery ifa pi *ui 3 J

Dram a* i 97^

ihi malifi^^il 3 3

nrttiluti ntaniir> iin(hc 3 1 9 A

external f nn of a?" llexuret |lc> 371 3 J internal f nn of sDi I 311 I myrt.naii n sC*) auin (fig lai) 3 /I \ritlrirlei sDi xexiclei I riinary 3f3 Dranci lal

arch 1^3 I «  arirtiei 153 i,0 c>»i4(liK 115) l<)7 rcunl nitxl i»( 137

Rri^vex emit lerfinl i^rj iiiraoilerm 57 ptuche* 173 Dranchiomeri'in 369 Dreajt ire Nlammar) Cland Drt ad livamrni of iiierui jjf Drt ncliial ancriei 15^

I udi 19II 109 miiiclei 3 Gj D rnnchui sot)

Duccinator inutcle 363 Durcopliar^ngeal membnne 4P 53 log 176




limb, 1 10 taste, 184 ureteric, 231

Bulb, olfactory, 279, 314 Bulbar

legion of heart, 147 ndges, 148 septum, 148

Bulbo-urethral glands, 251 Bulboventricular loop, 140 sulcus, 140 Bulbus cordis, 140 Bursa

mfracardiac, 222 synovial, 352

Caecum, 2 1 1 Calcified cartilage, 334 Calyces of metanephros, 232 Canal

alimentary, 176 archenteric. 49 atrio-ventncular, 140, 143 central, of spinal cord, 274 incisive, 18 1 inguinal, 255 irruption, 337 of Kurstcmer, 193 naso-palatine, 18 1 neural, 265

neurentenc, 78, 265, 387 notochordal, 49 pencardio-pentoneal, 56, 176 pericardio-pleural, 56, 220 pleuro-peritoneal, 56, 221 semicircular, 323 utero-vaginal, 241 Cancellous bone, 336 Capillaries, bile, 207 Capsularis, decidua, 68 Capsule Bowman’s, 230 Ghsson’s (of liver), 208 internal, 296 joint, 352 Jens, 318 optic, 344 otic, 344 sclerotic, 344 Cardiac, see also Heart

muscles, 138, 151, 355, 366 tube, 139 valves, 15 1

Cardinal veins, 139, 162 anterior, 139, 164 common, 139, 165 posterior, 139, 165 Cardiogenic area, 137

mesoderm, 52, 137 plate, 53

Cardio-v ascular system, iok C arotid arteries

common, 156 cMcrnal, 155. 156 internal, 154, 156


sinus, 158

Carpus, 338, 350 Cartilage, 97, 334 arytenoid, 348 bones, 334 calcified, 334 cells, 97

corniculate, 348 cricoid, 348 cuneiform, 348 differentiation of, 97 elastic, 334 epiphyseal, 338 fibro-, 350 fibrous, 334 hyaline, 334 hypophyseal, 343 Meckel’s, 345 otic, 324 parachordal, 342 Reichert’s, 346 thyroid, 348

Caseosa, vernix, 119, 370 Castrate cells, 34 '

Cataract, 319 Caudate

lobe of liver, 207 nucleus, 296 Caul, 80

Causal embryology, 124 Cavity

amniotic, 45, 70, 78 brain, 281 joint, 352

nasal, 115, 179, 180 pericardial, 56, 137, 176, 218 peritoneal, 56, 176, 221 pleural, 56, 176, 220 primitive buccal, 179 subgerminal, 388 tympanic, 189, 326 uterine, 61

yolk sac, 45, 75, 176, 389, 393 Cavum septi lucidi, 301 Cell, or Cells angioblastic, 136 blood, 99 cartilage, 97 castrate, 34

chromaffin, 270, 328, 329 decidual, 68 dendritic, 99, 371 endodermal, 45 endothelial, 99 ependymal, 266 fat, 99

formative, 383 ganglion, 270 germ, 6, 9, 378 germinal, 266 hepatic, 206 of hypophysis, 292 interstitial, of testis, 10 Kupffer, 208 luteal, 22 mast, 99

mesenchymal, 07, qo mesothelial, 96 muscle, 366

myo-epithelial, 355, 366 nerv'c, 267, 270 neuroglia, 266 neurolemma, 268

Cell, or Cells olfactory, 314 oligodendroglia, 266 oxyntic, 217 paraganglionic, 328 parathyroid gland, 191 parietal, 217 pigment, 99 plasma, 99 pregranulosa, 238 primordial germ, 236, 238 reticulo-endothelial, 99 retinal, 317 Sertoli, 10 sperm, 9

sympathetic nerve, 327 Cell islets of Langerhans, 210 Central

implantation, 60, 396 nervous system, 263-333 tendon of diaphragm, 221 Centre

diaphyseal, 337 ossific, 336 ossificaUon, 335, 337 of chondrocranium, 342 of viscerocranium, 342 Centriole of spermatozoon, 1 2 Centrosome of ovum, 41 Cephalic flexure, no, 277 Cerebellar cortex, 286 hemispheres, 285 peduncles, 286 Cerebellum, 264, 279, 285 differentiation of, 286 folia of, 286 Golgi cells of, 286 nodule of, 285 Purkinje cells of, 286 Tentorium, 279 Cerebral

aqueduct, 263 artery, 157 commissures, 300 cortex, 294, 297 histogenesis of, 298 fissures (Figs 321, 322), 298 flexures, no, 277 hemispheres, 279, 294 external form of, 294 internal orm of, 295 nerves, 306 peduncles, 288 sympathetic ganglia, 32° veins, 164 vesicle, 278 Cerebro-spinal fluid, 287 ganglia, 305 nerves, 304, 306 Cerebrum, 294 Cervical artery, 161 cysts (Fig 195)} t97 fistula (Fig tgs), 197 flexure, no, 271, 278 plexus, 305 sinus, no, n6, 197 vesicles, 197 Cervix uten, 242 Chambers of eye, 321


6 lot

C3if«-ki d'^rl pmrni o( II5 It'S Dietno-rfTfptnr* ijfl 330 Cli uma optic afli ay' 3f>a Chick y

Chic'iti » orean j(W Chontinficati n

ofaVulI 340

o(\riw»ta 33f)

aooJrohlat 07 Chofi jfocla't 337 Chooirocranuim 341 ChonlrocM p7 Q omlro^ nciii 334 Chof lai* i nJ n ar 151 Chofija tncjol la»t 13

mrvwl nil 3t5j

CJ on n Co -« 3^3

froniMum 4 lac\ 4

xaicul-iriiaiion ( r ,1 Chonon-^j Uh h ma C Chononic tar 71 ,0 mU 1

Cfion'>'\iiclhri plat nu 304 ClofoiJ 3* » plea ii 3il7

Chnruiialf luir 3)17 334 ofnc 3U ChromafTn hr«l> 333 cflli j « 3 f! 3:3 air m^rn.rt ai tjearcn of ) 4


chiarma ( rmadon of 19 dipt d numl>er of ill iiapi id numfier of 13 m d ( rntinaii n of tn in r rtil ration 41 in man 18 in maturation tli'i ion oru'uni

a a'ac

tn Jctrfrmnai 3W«  in Maracut fl etu 44 mcfollauc 3^1 un«4 i»t 3I • a ft patai la iPa OrfU

cnnt^r ital Canal 187

e 11 I R 1 *1

inter n urotp tir 3»l

, 3lt 937 951



n reduction 1

’ 357


in iprrmi igrnrtu 1 1 \and\ 1 1! 33r 937 Ciliary txxly 31b 3311 Circl of \\ dill lOo CirruJj tion

f)ian?e» m at hnti 171 cliorionif 71 foelaJ If j intemllous 71 pJarertaJ 83 portal 3i'9 Mtelhn 77

Circumferential tmplaniaii'in 3 Cijierna ch'li 1C8 Cijterna a8

Ciatsificaiion nf ner\e fibrra af8 Ciamirum 237 Clavicle 34J Lleavae 7 37 42 373 classiricai onj of 31 o determinate 3O0 d coidal 381 luration of iiagei 44 equal 380 lolollavuc 380

i en in! tmal 234 rat tna) 934 I u aea!

it> ml ran 4 t o J a ac 33 j C afcvK al

myotome* 3 3

V r1 Ira 3U C»el I a 333 iC«M ar rluci 33 4

n 'Y ^ ’

t CaieUae art rv ijR 3ifl Oie! m

I eatra-ernlry me 47 .

  • tntra^ml r> me jj 3


lay 93C

{looeler 38^

Coital tc tu| a nor 37

C« K»« (lour f I ftU 37 I C> II enne I iluct of pn nrphr tul uler of kiiney 938

Cm 11 cull 88

Oitolioma 317 a Ion 9»i Calotiruin 198 Commitiurai plate 30» Ooinmi nire •ni n r 701 f mtr 938 ioi 1 alH-nular ijii v t hippocampal 908 joi porterior 303 Ciimmon

cardinal \ein« 131 ifj rjaculatory duel 10 excretory duel 940 947 I I aiic duct 907 ' Comtnuniratinit raiiii 398 Ct mpael bone 33*’

Caimp lence i'»3 127 ' Comj lexily 0 Conchae naral iBa Cone crib of retina 317 Congenital cataract 3tg derormiiy

and malnuinin n I9g and maternal inrctli n

• 197 facta! cCeA 113 hvdrocephaliu 303 •aiocy 303 inguinal h rnia 935

CVinceniial pal v 3 14

poivcyrtic li ine> 33 3j8

,( >n3vsi\ctiv*l *»« 71*

' ( nn etifig iialV *n

(> nn etive linue /

Convo! Iletl lol der 333 933 C pula iPj t pulati n 3 Cor

I 1 -culare t 3 Iril irulafe i 2 l^rd

nepl roc m'" *

»eX 9J

ipnal '■3

timl I eal jf* n I* 3^0

vrlairenio junveft n rd ttj

C rl»

ImjIW 140 ret J a 1^3 9 I 0 l»n im 3 Cl a m a 7ici

iinu I4J ifT iileiii 9^1 a fpiH

all leant 7r talUuin -jR 1 t eav fft Ttiim iiietl ra jl lut urn 0 91 91 9I en 1 icrine funeti n of 93 livTierarmia < f 94 maiurtiy of 94 if ineniiruaii n 34 9 f paraluiral relit tf ■•4 ifpresnanoy 94 0

irgret inn ti 33 >|urium 94 vatcutariraiinn of 4 vervni 94

rtiiaium *■81 >4 995

fa r|i iKlrt

Matnig) lan 330 renal ••jo

cereliellar 2 t cercl ral 2 it aO? of luprarenal glaml 3 9 of ihymut gland irjj Curti organ • f 3 4 Cortici fugal fd res 29O Cornet petal filires 39O Cotyledoni of I lac nia 83 41x4 Louche Mirll gene 16 Cranial n rver 300 (raniopagut 132 Craniurn 310 Crest neural aCj 2C0 drnvaiivr* of 970 Cretinism 127 Cribriform plates 314 Cncoid canilaRe 348 Crista



Crown-heel length of embryos 105 Crown-rump length of embryos, 105 Crus commune, 323 Cryptomenorrhoea, 260 Cryptorchism, 256 Cumulus oophoncus, 16 Cuneate nucleus, 283 Cup, optic, 278, 289, 316 Curvatures of stomach, 204 Cushions, endocardial, 144, 146 Cutis, 370 plate, 371

Cuvier, duct of. 138, 164 Cycle

menstrual, 23 26 oogenetic, 23 ovarian, 23 prcgnani v, 22 uterine ..3 26 Cyclops, I ; 315 C% Stic due .o'"

C tst, or C\

branchial ■ 195), 197 ceivical (F y '93), 197 of kidnes - 238

thstoglossa IT urachal, 2O0 Mtclline {F‘g 2it , 216 C\toreticu!uin i C> totrophobl I'l 71

Decidua, bj, 67

relation of chi u i” mc to, 68 topograph ’ca’ ^ of 68 Decidual celts bli Deciduate placent Uion 69 Defects, congenital, 127 Dendrites, 267 Dendritic cells, 99, 371 Dental

cuticle, 375 lamina, 374 papilla, 374 pulp, 374 sac, 374 Dentate

g>'rus, 298, 301 nucleus, 286 Dentine, 373 Derivatives

branchial arch, 363 of diencephalon, 290 of ectoderm, 95 of endoderm, 96 of mesencephalon, 289 of mesoderm, 96 of rhombencephalon, 283 Dermal bones, 334, 341 Dermatome, 339, 355 Dermis, 370

Dermo-mvotomc, g6, 356 Descending colon, 211 Descent of testis, 254 anomalies of, 256 Determinate cleavage, 380 Determination, 121 of scK. 20, 237

Deutoplasm of o\um, 3, 37, 378 Dcutoplasmol>sis, 381 Development abnormal, 123

Development of bone, 334

Comparative Vertebrate, 377 and embryology, i experimental, 121 of external form, 107 factors in, 4 functional period of, 7 fundamental processes m, 6 heredity and environment in, 4 postnatal, 2

pre-functional period of, 7 prenatal, 2, 105 Developmental adaptation, 3 Dextrocardia, 173 Diaphragm, 221, 364 central tendon of, 221 muscles of, 222 Diaphyseal centre, 337 Diaphysis, 338 Diarthroses, 350 Dichorial twins, 131 Diencephalic gland, 293 Diencephalon, 263, 281, 290 glands of, 292 roof plate of, 291 Differentiation, 6, 122 auxano-, 122 de-, 122 histo-, 122 invisible, 6, 121, 122 of neural mechanisms, 312 visible. 6

Digestive system, 1 76 Digits, 1 14

absence of, 126 Dioestrus, 33 Dionne quintuplets, 132 Disc

“A,” 367

bilaminar embryonic, 46, 48

“I,” 367

intervertebral, 339 optic, 320

trilaminar embryonic, 48

“Z,” 367

Discus proligerus, 1 7 Diseases

congenital, 127

in production of anomalies, 127 Diverticulum

allanto-enteric, 70, 76, 176 Meckel’s, 215 pineal, 293 thvroid, 196

Division, reduction, ii, 18 Dizygotic twins, 13 1 Dorsal

aorta, 152, 154 double, 173 hp of blastopore, 386 mesentery, 204, 223, 385 mesocardium, 139, 218, 220 mesogastnum, 204 pancreas, 208 sacral ligament, 35c Double

dorsal aorta, 173 monsters, 132 penis, 260 Duct, or Ducts

allanto-entenc, 70, 76, 176

Duct, or Ducts amniottc, 79 cochlear, 324 of Cuvier, 138, 164 cystic, 206

ejaculatory, 10, 241, 259 endolymphatic, 323 of epididymis, 241, 259 excretory, common, 240, 247 Gartner’s, 241 hepatic, 207 lactiferous, 372 mesonephric, 228, 236, 240 Mullerian, 227, 236, 240 transformation of, 240 naso-lacnmal, 115, 182, 322 paramesonephric, 227, 236, 240 of Santorini, 209 thoracic, 168 thyro-glossal, 196 utnculo-saccular, 323 vitelline, 215 Wirsung’s, 209 Wolffian, 236 Ductuli

aberrantes, 230, 231 efferentia, 13 Ductus

arteriosus, 156 persistent, 173 caroticus, i‘j 6 endolymphaticus, 323 pharyngo-branchiahs III, 19° pharyngo-branchialis IV, 194 reuniens, 323 venosus, 140, 169 Duodenum, 202, 204

mesenterial fixation of, 163, 205 suspensory muscle of, 205 veins of, 163 Duplex monster, 132 Dura mater, 320

Ear, 1 14, 322

external, 114, no, 325 internal, histogenesis ol, 323

middle, 189, 325

muscles of, Table HI) 3^3 )7r*^#»n#Tir imnlantation. 6o, 39

Ectoblast, 125 Ectocardia, 365 Ectoderm, 7, 45, 3°3 derivatives of, 95 formation of, 45 neural, 266

Ectodermal placode, 263, 3


cordis, I73> 219 vesicae, 252, 260, 305 Ectopic gestation, 69 Efferent

nerve fibres, 284, 3*2

irons, 274 ree Ovum


cartilage, 334 fibrils, 97



due 4G 48

roembranej Embryo orlttibt^tH

oUbU^i^ent m niucma C2 I pippricAT^iaJ ruJ?*- no

estimation of atje of lo^ 1 piphwal

eilemal form oi human 107 cariita?e JS*)

foetal Jtas of 1I7

gro\»th changes in 104 rpiph>ti* 338

implantation in ectopic sites 69 Epiploic foramen (riTWinsIm ) 2}3 m asufem nt of 105 Lpuna has 35* aw»

preparation of uterus for a6 1 pUhaUmu aOj 3y»

presomiie 107 f pithelio-chsnal plaeenia C<» 4»J

somite 107 LpithelioCMri 97

sveighl of io| fptileJium

mlrjDlosy ofUadder a 47

I pidid^tnts

sasaefrerenluof ic* 330 341 250 r pitjenesis 6 rpiglsitis 183 iD| 109

1 piloia 137

presomiie 107 somite 107 weight of io| Eml T4 olosy causal 134

descnpii'e ”• experimental a scope of a stages of 6 suUiMsions of 3 \afue of a Embr>otrop'he Ci Enamel la)er 373 orijan 3?4 Endocardial eushiorti 144 146 tiHue 149 Endocardium 133

coelsroic 336 ofrorriea 319 germinal I4 of lens 31O meiltillar) aGf mrsench> mal of inner car 324 ofifis 331 of oesoptiai^us 303 olfa<tor> 314 Tespvr»tor> 300 of retina 317 leniory aCj of tioinacli 3iC of uterus 93 i piirichium 370 Ipoophoton ducts of 341

Endoenne I riihroblastcnis (beialis 129

fartors in faulty drselopment isO I rytlirolilasts <>9 3o8 333 function of corpus luteum 23 Trsthrocyles 99 308 335 Endodertn 7 383 Fihmoid bone 314

Endoderm 7 383 denistitejof i

formation of 4$ 384 primary 45 3U4 |

secondary 383 Endolymphatic duct 323 Endometrium 33 changes in aG

m menstruation 37 I

phases of 6 strata of 37 EndoslieJfion 334 Endothelial cells 99

heart tube 54 137 Endothelio-chonal placenta Go 403 Endothelium 135 EntoUast 1 5 Entwickslungsmeehanik a Eniypy 392 397 Environment heredity and 4 Eosinophil cells 99 Epartenal bronchus aoo Ependyma]

Cells 38r layer 267 Epibolv 386

Epibranchial placodes 263 310 Epicardium 138 Epidermis 370 Epididymis 4s

appendix of 341 359 efferent ductules of 10

Fihmoid bone 314 Fustachisn lube 190 325 32G Futhcfia 391 implantation in 39G ptaeentaiinn of yolk sac of 391 FsocatioP 134 I locator I2| r volution of sex 9 Exoeorlom 4C

I xocorlomic membrane 4O 75 I xomphaios 314 Fxperimenial development 132 Implantation 3 I xtemai

auditory meatus no tSq 333 ear 114 it6 335 factors m dev clop ment 4 genitalia 347 349 female 232 male 351 glomerulus 338

Exira'cmbryonic coelom 47 53 310 membranes ^ mesoderm 45 46 r stra uienne pregnancy 69 Eye 315

accessory structures of 331 chambers of 330 331 intraocular vessels of 319 median 137 315 muscles 331 3C0

Eyelaihfs 31C 317 'Lychds 114 331


cl ft congenital 115 tr7 gangl on •’Gg nerve 15 3,0 3of jio

nucleus 2B5

Valciform I gamrnt "04 Fallopian tulie 340 lalx cerebri 370 ■’0}

Fa'fia 3 j 5 3b!

lumbar 358 Fat 99 308 Fauces ani Faucial tonsil 190 lemale

external genitalia 2j2 gona I 238 pronucleus 3, 40 lemoral artery 1G3 Fenestra vestil uli 32G Fertility 40

Feriilizati nib o 32 3/ 40 age 104

derinilinn of 37 40

optimum time for in menstrual

lens 318 inusrlr ^GC nerve 3WJ neuroglia 2GG Fibrils eiasiir 97 muscle aCG nerve 267 Fibroblast 97 Fibro*cariilage 350 Fibrocyte 97 Filiroui cartilage 334 Field Forces 124 Fifth ventricle 301 Filaments of ipermaiozoon I3 Fihfoim papillae of tongue 1B4 Filum terminate 372 Fimbria

ofliippocampus 398 301 of uterine tube 39 241 Fingtn

anomalies of 126

antero-median 274 central 298 choroidal 287 294 of eye jiG foetal 316

hippocampal 295 398 lateral (I ig 321) 298 lung 200 ^ rhinal 398 301

cervical (Fig 195) 197 urachal sGo urinary (Fig 25?) 348 vitelline (Fig atG) 3t6



Flagellum of spermatozoon, 1 2 Flexure, or Flexures cephalic, no, 277 cervical, no, 271, 278 midbrain, 273, 275, 278 pontine, no, 277, 278 telencephalic, 277 Flocculus cerebelli, 285 Fluid

amnio tic, 78, 81 cerebro-spinal, 287 seminal, 38 Foetal age, 105 circulation, 169 development, 117 fissure, 316 gut, histogenesis, 216 membranes, 69, 389 bilaminar, 70 unilaminar, 70 in amniota, 390 in anamniota, 390 movements, 119 Foetus, 117

external forni of establishment of, 117

groivth chanc;'=’s of 119 Fold amniotic genital. ->3glosso-' , 1“ lue 185 head, m inguinal 23- ,

lateral bod> 79 lateral nasal, 114 179 medial nasal 114, 179 neural, 108 269 pericardio-pleural, I42 tail. 76, 79

Foliate papillae of tongue, 184 Follicle

Graafian, 16 ovaiian, i^i, 16 atresia of, 23 polyovular, 13 1 primary, 15 rupture of, 17 thyroid, 197 Follicle cells, 15, 22 Follicular

epithelium, 15 fluid, 17, 22

phase of endometrium, 26 Foot, 114 Foramen

caecum 183

epiploic (of Winslow), 223 interv cntncular of brain, 281 of heart, 148, 172 ugular, 344 ■ magnum, 343 optic, 343

ovale, of heart, 145, 170 closure of, 145 patent, 172 valve of. 145 ovale, of skull, 344 pnmum, 144 roiundum, 344


secundum, 144 Forebram, 109, 263, 278, 289 Foregut, 55, 77, 176, 177 caudal portion of, 202 cranial portion of, 1 78 Forehead, development of, 117 Formative cells, 45, 383 Fornix, 298, 301

commissure, 298, 301 system, 298 Fossa, ovalis, 145 Fourth ventricle, 280, 281, 287 Fraternal twins, 5 Free-martin, 245 Friedman’s test, 90 Frontal bone, 344 lobe, 280, 295

Fronto-nasal process, 114, 180 Froriep’s ganglion, 307 Functional period of development, 7 Fundamental concepts, i— 8

processes in development, 6 Fundus of uterus, 242 Fungiform papillae of tongue, 184

Gall bladder, 246

Gametes, i, 9 Ganglion, or Ganglia acoustic, 323

acoustico-facialis, 310, 323 auditory, 269 cells, 270

cells layer, of retina, 317 development, 270 facial, 269, 310 Fronep’s, 307 geniculate, 310 glossopharyngeal, 269, 31 1 intermediate, 328 nodosum, 31 1 occipital, 269 spinal, 269 superius, 31 1 sympathetic, 327 terminate, 314 trigeminal, 269, 309 vagus, 269, 31 1 vestibulo-cochlear, 323 Gartner’s duct, 241 Gastrocoele, 384

Gastro-hepatic omentum, 204, 208 Gastrula, 7, 383 Gastrulation, 7, 383 in Aves, 388

double, as cause of twins, 1 3 1 in Fishes, 387 in Mammals, 389 in medialecithal eggs, 386 in megalecithal eggs, 387 in miolecithal eggs, 384 in Reptiha, 388 Genes

abnormality due to, 126 autonomous, 126 dominant, 126

environment and heredity, 4, 126


heteronomous, 5, 126 homozygous, 5, 126 recessive, 126 role of, 4 Genetic

relationships, i variations, 5 Genic balance, 257 Geniculate bodies, 291 ganglion, 310 Genital

blastema, 236 ducts, 240 fold, 234 organs, 227 ridge, 236 swellings, 250 system, 235 tubercle, 250 Gemtalia

anomalies of, 257, 2 '58 derivatives, 259 external, 247, 249 homologies of, 259 internal, 236

Gemto-urmary system, 211. 227-202

Genotype, 5


cells, 6, 9, 378 female, 14 male, ii

primordial, 236, 238 layers, 7, 44, 330 derivatives of, 95, 96 in development, 124 inversion of, 392, 397 Germinal cells, 266 epithelium, 14 Gestation, 26

extra-uterine, 69 period m man, 104 Gill clefts, 178, 179 Gland, or Glands Bartholin’s, 253 bulbo-urethral (of Cowperj, 251 diencephalic, 293 lacrimal, 321 lymph, 169 mammary, 372 parathyroid, 189, 19I) *94 parotid, 188 pituitary, 34, 278, 292 prostate, 249 salivary, 183, 187 sebaceous, 119, 372 Skene’s, 249 sublingual, 183, too

submandibular, 183) to7

suprarenal, 329 sweat, 372 tarsal, 321) 372 thymus, 189, 192 thyroid, 183, 189, 19° vesUbular (of Bartholin), 253 Gians

clitoridis, 252 penis, 251

Ghsson’s capsule, 208 Globus paUidus, 297



Ciomfru)us 258 niwonfphne 230 mrtanephric 232 proncpfinc 29 Glomus coco 5fum iCi Glosso-cpiglottic folJ Glossophaongpal nerie f57 2/3 3^ 310 ganglion 311 Golgi apparatus ofo'um tC of sperm t2

Gonadotrophic hormones Gonads 1 Q 52 236 245 descent of 254 histogenesis of 237 ovary 238 2j6 testss 337 35*

Graafian follicle 16 Gracile nucleus 283 Granular layer of cerebellum aSG Grey matter of spinal cord 2G8 274 Groove

branchial lyq tinguo-gingival iQ^ neural 51 108 264 pharyngeal 109 173 tSg ectodermal 109

endoderm^) tfff first 190 second 190 tliird 190 fourth iqi fifth 194

_ uacheo^bronehtal igi iSi GroMth G

accretionary 6 104 auxeiic 6 104 ehang s loi intussu cepiive C multtphcative 6 10^ postnatal 3 p enaral 2 J04 m weight 1 04 Gubcrnaculum dentis 375 of ovary 56 of teeth 375


abnormal development of 214 acres a of 215 blood supply of 217 enzymes of 216 fixation of 213 Jorc 55 ,77 17C 202 lunctional activities of 216 n'nd 77 t<6 211 234 histogenesis of 21b 77 177 2to

return of to abdominal cavity ■’i lotationof 163 212


Habeauto-pcduncular tract ->90


tnnnophNleiic theory of 99 102 polyphylelic llwory of to Haemivchonal placenta Co Sj 402 404

llaemo^loblast 99 Haemo-cndoihclial placenta 60 402 Haemoglobin 101 HaemoKtnph glands 169 Ilaemolvtic durase of newborn 129 Haemorrhage mensirtial 23 29 /faemotrophe 71 Hair 117 372 follicle 37'’ lanugo 117 372 vibnssal 117 Hand 114

anomalies of (Fig 390; 352 Hard palate 181 Harelip 115 127 lO 1C6 Hassal s corpuscles iCj Head

foltl 54 76 muscles 360 of pancreas 209 pfoeesi 49 ofspermstoroon 13 vein primary 164 Heart /j? annulus ovahs 145 anomalies of 172 atrioveninculae canal 140 143 valves 151 atrium 140 143 »?s auricular appendage 143 bulbar ridges 148 bullio-ventncuiar loop and sulcus 140 changes at birth 171 ensta lermiftahs 14C deiecotof 154 173 duciut tenosus >40 rCo endocardial cushions 144 14G endocardium 139 external changes 140 foramen

interventricular 148 ovale 145 primuin 144 Secundum 144 fossa ovahs 143 histogenesis of ijl 353 36b innervation of 330 intersepto valvular space 143 miervenous tubercle 146 I mbic band 1^6 mesenteric relations (Fig 227; J25

mcsocardium 139 218 '>20 musculi peciinati 147 myocardium 138 151 3C6 niyo*rp cardial mantle 138 151 2t8

papillary muscle 151

pars membranacea septi 190


interventricular 148 pnmutn 143 secundum 145 spurium 143


iinu atnal orifice 141 sinus venosus 138 I4f 145 t82 venous valves 141 ventncle 123 140 t47 wall differentiation oi 137 Heat penod of 22 Helicotrema 324 Jlcmwphercs cerebellar 283 cerebral 279 294 Henie s loop 233 Henren 1 lines 367 node 49 383 Hepatic artery 218 cells 206 circulation 209 duels 207 rudiment 20b sinusoids t{>3 207 trabeculae "OG Hepato-cardiac channels 163 Hereditary

malformations 127 relationships 1 Heredity and environment 4

as factors m faulty development, tsC

Hermaphroditism 237 Hernia

(iiaphragmatic 221 inguinal 255 Heierolaxis 173 H u rr s menibrane 46 Hillocks auricular iib 325 Hindbrain 110 aCj 83 Hindgut 77 17& 211 Hippocampal eomriimure 208 Fiuurr 9 j 298 Hippocampus 295 297 298 Htfschsprung s disease 2f5 Histiocytes 90 Hiviogcnesis b of blood 99 of hone 97 334 of cartilage 97 of cerebral cortex '•98 of connective tissue qj of corpus luteum 24 of digestive tube "16 of foetal gut 21C of gonads 237 of heart 151 355 36b ofinlcmalcar 323 of muscle 366 ofnervous ti sue 263 of piniliyroid 193 of retina 317 of skin 370

Holoblaslic cleavage of ov-um 380 Homol0(,ues of genital svvtcrns 259 Hormone 9 Cb anterior pituitary 34 corpus luteum 3 follicle stimulating 34 gonadotrophic 23 34 lutcalizing 34 morphogenetic 124 ovarian 23



Horse-shoe kidney, 233 Human embryos, see Embryos Humour

aqueous, 321 vitreous, 319 Hyaline cartilage, 334 Hyaloid artery, 318 Hydatid

of epididymis, 241, 259 of testis, 243, 259 H^datidiform mole, 67 Hydramnios, 82, 92, 184 Hydrocephalus, 303 Hymen, 243 imperforate, 260 Hvoid

arch, 109, 153 bone, 347, 363 coinua, 347, 363 muscles, 363 H/perdactihsm, 126 Hypobranchial eminence, 182, 183 Hypoglossal

nen'e, 278, 306, 307 Hypomeie, 357 Hypophy’seal cai tilage, 343 Hypophysis cerebri, 34, 278, 292 cells of, 292 hormones of 34 lobes of, 290, 292

relationship of ivith sex cycle, 34 stalk of 292 Hypoplasia, 126 Hypospadias, '51, 260 Hypothalamus i;, 280, 282

“I” disc, 367 Identical twins 5, 130 Ileum, 210 Iliac

artery, 159 lymph sac, 168 vein (Fig 157), 166 Impar, tuberculum, 182 Imperforate anus, 215, 250, 260 Implantation

of blastocy St, 60, 62 comparative, 377 in Eutheria, 396 sites of, 69 types of

central, 60, 396 circumferential, 396 eccentric, 60, 396 interstitial, 60, 63, 396 orthomesometnal, 396 superficial, 61, 396 Inasivc canal, 181 Incisura temporalis, 301 Indeterminate cleavage, 380 Indinduation, 124 Incus, 325, 347 Induction, 123 Indusium gnseum, 301 Infcnor vtna cava, 145, 163 Infracardiac bursa, 222 Infundibulum

of hypothalamus, 290 of utenne tube, 39

Inguinal canal, 255 crest, 255 fold, 237, 254 hernia, 255

Inheritance, cytoplasmic, 4 Inner cell mass, 43, 70, 382 Innominate artery', 156 vein (Fig 157), 166 Insemination, 22, 37 Insula, 280, 295 Interatrial foramen, 144 septum, 143

Intercostal artery, 159, 161 Intermediate ganglion, 328 mesoderm, 52, 159, 227 Intermenstrual loss, 33 Internal

capsule, 296

carotid artery, 154, 156

ear, 322

factors in development, 4 jugfular vein, 165 Interneuromeric clefts, 281 Interosseous artery', 162 Intersepto- valvular space, 1 43 Intersex, 257

Interstitial implantation, 60, 63, 396 Interthalamic connexus, 291 Intervenous tubercle of Lower, 146 Interventricular foramen

of brain, 281 of heart, 149 septum, 148 sulcus, 147

Intervertebral ligaments, 339 Intervillous circulation, 71 space, of placenta, 71 Intracartilaginous ossification, 334,



coelom, 53, 210, 218 mesoderm, 48, 50

Intramembranous ossification, 334, 335

Intraretinal space, 317 Intra-utenne

amputations, 126 infection, 127 Intussusceptive growth, 6 Inversion of germ layers, 392 Involuntary muscle, 355, 365 Ins, 316, 317, 355 epithelium of, 316 muscles of, 366 stroma of, 317 Irruption canal, 337 Islands, blood, 71, 76 Islets of pancreas, 210 Isthmus

of brain, 278

of thy roid gland, 1 90

Jacobson’s organ, 314 Jaw, 178, 344, 363


lower, 185, 347 upper, 178, 180 Jejunum, 210 Jelly, Wharton’s, 80 Joint, or Joints, giyo capsule, 352 cavity, 352 disc, 351

synovial, 350, 351 Jugular

foramen, 344 lymph sac, 168 vein, 165

Kidney, 228

anomalies of, 233 calyces of, 232

congenital polycystic, 233, 258 horse-shoe, 233 pelvis of, 233 tubules of, 228 Knot, primitive, 49 Krause’s membrane, 367 Kupffer cells, 208 Kursteiner, canals of, 193

Labia, 253 Labial swellings, 253 Labio-dental lamina, 185 sulcus, 185 Labio-gingival lamina, 374 sulcus, 185

Labio-scrotal swellings, 250 Labour, onset of, 90 Labyrinth, membranous, 324 Lacrimal

bone, 344, 348 gland, 321 sac, 322 Lactation, 26 Lactiferous ducts, 372 Lacunae bone, 336

in trophoblast, 63, 7 ® Lamarckian, 5

ar, 272, 283, 285 isal, 272

loroidea epithehahs, 207

mtal, 374 ,

bio-gingival, 374

rmmahs, 277, 3°°

gerhans, islets of, 210

ghan’s layer, 62, 71

ugo hair, 117, 37^ _

mgeal nerves, recurrent, 57 '

158, 31 L 363 mx, 198, 199 irtilages of, 199 uscles of, 199 ' 383

rves of, 199 ) 3 **' 383

iniculatc bodies, 29^ ey columns, 273 version, 132 isal folds (process), II 4 '


plate mesoderm 5 th)roid 193 igj

'entnde of brain aSi ■'89 Uw biogenetic of recapitulation

ameloblastic 37^ enamel J73 ependymal 366 Mnglioncell of retma -tty Langhans 6 71 '

mantle 67 marginal 07 nertous of retina 317 odontoblastic 37^ pigment of retina iio Leg '

anenes 163 bones 349 daefopment of 310 muscle? 36


at birth 120 ofembrjo J03 115 317 c»t»ule 318 epitheLum of 318

«be« 3,8 Pl»c^e Its 3»fi

^rtflJureofitomaeh aoa ontentum 20J 323 ’

15:;“."?' “

««coc)topoiesu joi

wenorenal ligament 3J4

coronary 208 sacra! 3.9 i^lciform 204 ao3 8«trospl«nic 32«  intersertebral 330

i^nc^renal j 4-^^^

°[l'\er 203


triangular 208 urnbilcal 172 H?atienta flava 3,0

l™?”™ >7.

, muscles 362

i;»b.cb„d. ,,6 33»


t Linea alba iC-i ^ Lingual

rpithebitm *84 pnmordia 182 I tonsil jpo Ltnguo-dmial sulcus 18,

I Ijnguo-gingival groo\c 16. Lip 182 ' rlefj »Cf

furrow band i8j 3-4 bare 115 ,27 ,81 ,£5 /"*««■

rhombic 28 j upper i8j Liquor

of amnion ,8 8c , follieub 17 ,8 Litter mates 130 Liter 20^ jo6 capsule of 208 tells ao6 cords 207 ducts 207

harmatopriesis in 100 02 Kupffer cells of 208 '

ligamenii of 208 lobes of 207 IIRUSOlds of 307 Lobes

of cerebellum aBj of cerebrum 20j ®5 *t>popbMu 2<K> ep offiser 207 I of lung 900

Libules of placenta 8» Longitudinal bundle medial 260 I sympathetic trunks 9 7 I I-®op '

ffenles 233

I intestinal limbs of 12 I extremits blood sessets of 162 bones of 349 development of 340 muscles of 36-’

I nerses of 30,

Lumbar arteries 159 nerves 305 I veins 107

1 Lumbo-cosul Veins 16-.

I Lumbo^cral plerus 30^

t-ung 198 alveoli of 198 bud 199

changes at birth '*ot fissures of 200 lobes of 200 I weal

cells 22 24 hormone 32

phase of endometrium

. Lucem 94 I Lymph

gland 169 sac iliac 168

Mmphaiic rystcm 168 I Lymphoblast lot 160 Lymphocyte 99 ,0, Lymphocytopoies s 101

Lymphoid arra

“Miiimocytopoies s 101 j 6 o

L>-mphoid area of tongue 1^

Macaeua rhesus cleavage m 44 implantation in 6j Macrophages 90

'lacTostomia 187 Macula saccular 324 utncular 324 'fagma reticulare 47

CCS of kidney ->32

I external genitalia of 2,1 I gonad 237 I pronucleus 41 'falformatJons 13^ of^mto-urinary svstem 2,8 of heart 173 *'

,®f nervous svstem 302 Ma feu, 325 34G Malnutrition 129 I Malpighian corpuscle, 230 viammary arter\ internal 160 gland 372 alveoli of 373 lactiferous clucU of 372 rupernumenry 373

line, 37J 37 J

Mamiflarv bodies 998 Mandible 348 Mandibular acch tog 153 ntne 309 process 109 178 3.3

Mam). la>er 867 Manubnum sterm 340 ^larginal

imus of placenta 84 zone 267 +

I Marrow

borte tot 336 i cavuv 335 Manupialia 393 placentalion m sn,

^ >olksacor 393 ^lasi cells 99 Mastoid air cells 3 5 I antrum 3 6 Maternal

grey 374 irhife 274

Maturation 6 ofhuman ovum 14-20 ofoogonmm 18

I Maxilla 348 '

Maxillary nerve 309

process toq 178 34,

i sinus 18

«f l.™.« tmbrjo,

•external aud.toiy ,to ,80 ,2. tntemal auditory 344 ®



Mechanical agencies in production of anomalies, 126 Mechanocytes, 97 Meckel’s

cartilage, 345 diverticulum of ileum, 215 Meconium, 208, 217 Medial

lemniscus, 269 nasal fold (process), 114, 179 Medialecithal ova, 378 cleavage in, 380 gastrulation in, 386 Median

aperture of IVth ventricle, 287 eye, 127

fissure of spinal cord, 274 postero-, septum, 274 Mediastinum ovarii, 238 testis, 10, 237 Medulla

oblongata, 264, 278, 282, 283 of suprarenal gland, 329 of thymus gland, 194 Medullary cords, 237 epithelium, 266 velum, 287, 288 Medulloblasts, 266 Megakaryocyte, i o i Megalecithal o%a, 378 cleavage in, 380 gastrulation in, 387 Megalocytc, loi Meiosis, 6 1 1 Melanin, 371 Melanoblasts, 99, 371 Membrana propiia, 17 Membrane or Membranes anal, 58, 212, 235, 250 bones, 334, 336

buccopharyngeal, 48, 52, 56 109, 176

cloacal, 49, 57 79, 21 1 egg, 379 embryonic, 389 e\tra-embry'onic, 6g, 389 foetal, 69, 389 granulosa, 16 Heuser’s, 46 Krause’s, 367 Nasmyth’s, 375 placental, 60, 85, 402 pleuro-peritoneal, 220, 222 pupillatv', 319, 321 persistent, 321 Rcissner’s, 324 rupture of, 80 synov'ial, 350, 352 tcctonal (Fig. 355), 323 Umpanic, 325

urogenital, 58, 212, 235, 250 vestibular, 324 v’ltelline, 16, 37 Membranous labynnth, 324 Meninges, 95, 270, 287, 342 Mcningocoele, 303 Mcninx, 342 ecto-, 342 endo-, 342 KIcnisci, 352

Menses, 26 Menstrual age, 104 cycle, 23, 26 length of, 19 phases of, 26 flow, 26

phase of endometrium, 26 source of, 30 Menstruation, 23, 26-28 in adolescence, 29 anovular, 29 cause of, 30

corpus luteum of, 24, 26 haemorrhage during, 26 histology of, 29 length of, 26 relation of oestrus to, 33 relation of ovulation to, 3 1 Meroblastic cleavage of ovum, 38 1 Mesectodermal cells, 95 Mesencephalon, 109, 263, 277, 287 differentiation of, 289 Mesenchyme, 71 derivatives, 96 Mesenchymal cells, 97, 99 Mesenteric

artery, 77, 158, 210, 218 lymph sac, 1 68 vein, 164 Mesentery

dorsal, 204, 385 fixation of, 213 ventral, 204, 223, 385 Mesoeardmm, dorsal, 139, 218, 220 Mesocolon pelvic, 212 transverse, 214, 225 Mesoderm, 7, 45, 99, 385 axial, 52 branchial, 57 cardiogenic, 52, 137 chorda-, 385 chorionic, 70, 71 derivatives of, 96 extra-embryonic, 45, 46, 405 formation of, 45 intermediate, 52, 159, 227 mtra-embryonic, 48, 50 lateral plate, 52, 227 paraxial, 52, 227, 339 parietal, 47 primary, 47, 405 somatopleuric, 47, 53, 364 splanchnic, 47, 53, 364 splanchnopleuric, 47, 53, 365 visceral, 47, 365 Mesodermal

somites, 52, 107, 339, 355 syndrome, 127 Mesodermic pouches, 385 Mesoduodenum, 205, 213 Mesogastrium

dorsal, 204, 223, 385 ventral, 204, 223, 385 Mesonephne corpuscle, 230 duct, 228, 236, 240 fate of, 236 fold, 230 glomerulus, 230 mesentery, 230

Mesonephric tubules, 228 vesicle, 230 Mesonephros, 227 differentiation of, 230 epigenital part of, 230 functional activity of, 231 in man, 230 paragenital part of, 230 phylogeny of, 227 Meso-oesophagus, 203, 222 Mesorchium, 237, 255 Mesothelium, 96 Mesov'arium, 237 Metabolism, 6 uricotelic, 4 Metamerism, 107 Metanephric artery, 159, 233 bud, 231

Metanephric blastema, 231 Metanephros, 228, 231 anomalies of, 233 calyces, of, 232 collecting tubules of, 232 functional activity of, 234 glomerulus of, 232 histogenesis of, 232 tubules of, 228 ureteric bud, 231 Metaplasia, 123, 253 Metathalamus, 291 Metatheria, 393 yolk sac of, 393 Metazoa, i

Metencephalon, 263, 278 Metoestrus, 33 Microglia, 266 Microstomia, 187 Midbrain, 109, 263, 287 Middle ear, 189, 325 Midgut, 77, 177, 210 Migration of ovum, 40 Milk

ducts, 372 line, 373 ridge, 373 Minor calyces, 232 Miolecithal ova, 37> 37^ cleavage in, 380 gastrulation m, 384 Mitochondria of ovum, 16 Mitosis

in oogenesis, 19 in spermatogenesis, 19 Iitral valve, 151 Iittelschmerz, 33 lole. hydatidiform, 67

Monochorial twins, 131 Monocytes, gg, loi

Monoestrus, 22 Monophyletic theory ol poiesis, 99, 102 Monoplegia, 303 Monozygotic twins, 131 Monro’s interventricular


Monsters, 125, 13*

organizing centres in, 1 Siamese, 13 1






Niorphogenelic hormonw 124 movements 7 363 MoruU 43 6j 380 jije of bi

Mosaic ]»uetn I2t Motor

end p'ate 3t>6 nenes

somatic 274 30O viscera) 274 2^4 3 t)P nucleus

of Spina) nerves 3/4 of irigemma) nerve aOj of vagus nerve 284 Mouth

development of 181 floor of 162 primitive 57 115 roof of ! >9 Mucosa uterine 23

implantation of embrjo in 60 in pregnancy 63 67 penetration by embryo f2 Mullerian

ducb 227 2315 240 transformation of 240 tubercle 242 Multiparous uterus Gt Multiple births (tee Twtnnitvg Multiplication cell G Multiplicative growth 6 104 Muscle or Muscles 3 jj“ 368 of abdomen 3 G of auditory ossicles 363 JVKk 5,G 35B oTbUdd r 248 bronchia] 36^ buccinator 3P3 cardiac 131 355 361 ciliary jfti cotc)gevis 360 ofduphfajm 364 digavtnr 363 of duodenum 203 of expression 363 of eye 221 360 facial 363 fibres 36(1 fibrils 366 geniohyoid 360 ofhead 360 hisfogcncsia of 3C6 ilio-cosiahs 358 infrahyoid 360 intercostal 359 intervertebral 358 ofmtevtme 365 intracostal 359 involuntary 355 36^

355 36b levator am 360 of limbs 362 {onps imus 358 lumbar 359 masseter 363 of mastication 361 mulljfidus 358 mylohyoid 303 ofnecx 360

obliquus abdominis neo of palate 363

Muscle or Muscles

papillary *5*

penncaJ 360 pharyngeal 361 prcvertebral 360

pteoi?^*^ 3G3 pupillary 355 3®® quadratus iumborum 3^9 rectus abdominss 359 roiatores 358 sacrospirsalis 359 scaJenei 360 segments 355

semispinalw 358

skeletal 355-369

smooth 355 36* spindle 36f splenius 3jB superfial 363 iternatis 359 siernomastDid 363 sinate 35^ sivfobyoid 363 siylopharyngeus 3G3 temporal 3G3 tensor tympam 363 tongue 3Cn tracheal 3G5

traniveesus abdomims 359 tratuvenus ihoraeis 359 irapetius 3C3 of trunk, 359 of vertebral column 358 visceral 355-3G9 vulunrary 355 367 Muscular system 355-369 Musculature origin of segmental (Tabic 11; 356 ongiftotvisceral arch (Table 111) 363

hfusculi pecimati 147 MyeJencephalon 263 37B nuclei of 283 Myelm

developmeniof inspmalcord 2C8 sheath 2C8 Myelination 268 Myeloblasts 09 Myelocytes of Wood los Mvoblajts 138 356 Myocardium 138 s^t 3jj Myoeoele y'

Myoepicardial mantle 138 2|8

Myo-epiihelial cells 355 3(16 Myofibnls 366 Myotome 339 3,5 cervical 360 coccygeal 359 demo- 96 35G head 360 lumbar 359 occipital 184 360 sacral 359 thoracic 356

Nall 117 371 fields 37s Nares

anterior 114 1 posterior 180


bone 344 3^8 capsule 314

cavities I" ' conchae 1 folds (processes) J *-1 * I placode U4 179 3«4 s ptum 180 sinuses tSz

Nasmyth 1 membrane 375 Naso-lacrimal

duct 115 182 322 furrovv 115

Naso-palatine canal t8» Nasopharynx 201

Neck 114 Netghbounvise 721 N oeoftex 297 298 Nco-Laroarcltian j Neopallium 295 297 302 Nephric system phylogeny of 227 Ntphrocoele 228 Nephrogenic cord '’27 Nephron 233 Nephrosionte 228 Nephrotome 228 Ncne or Nerves abducent 279 306 308 accessory 278 30C 312 acoustic 270 auditory 306 3a cells histogenesis of 67 2/0 cerebral 30C cerebro-spinal 304 306 cervical 303 chorda tympam 326 cochlear 3 3 crania) 209 306 elTerent

somaiir 30G 31a visceral

branchial 209 311 general 306 311 special 30G 31 1 facial J57 279 3°®


fibres 268

glossopharyngeal 157 278 306 310

hypoglossal 278 306 307 laryngeal 157 15O 3ti 363 lingual 310 mandibular 309 maxillary 309 motor somatic 274 308 oculomotor 306 308 olfactory 30b 314 ophthalmic 309 optic 269 306 315 317 petrosal 310 phrenic 222 304 pi xuses

cervieo brachial 303 lumbosacral 305 post irematic 178 pre cervical segmental 307 pre trcmauc 178 profundus 309 somatic

afferent 306 effer nt 3^ 312



Nerve, or Nerves spinal, 304 accessory, 312 rami, 304 roots, 304

trigeminal, 157, 279, 306, 309 trochlear, 306, 308 vagus, 278, 306, 31 1 vestibular, 269, 323 visceral, 306, 309, 311 vomero-nasal, 314 Nervous system

autonomic, 327 central, 263

development of function in, 312 parasympathetic, 327 peripheral, 269, 304 sympathetic, 327 tissue, histogenesis of, 265 Nervus terminalis, 314 Neural canal, 265 crest, 263, 269 ectoderm, 266 fold, 108, 269 groove, 51, 108, 264 mechanisms, differentiation of, 312

plate, 109, 263 supporting elements, 266 tube, 109, 263, 265 anomalies, 303 derivatives of, 269 histogenesis, 265 Neurenteric canal, 78, 265, 387 Ncuroblasts, 267, 327 differentiation of, 267 of retina, 3 1 7 Neurocranium, 341, 342 cartilaginous, 342 membranous, 344 Neurocranium regions of, 342 sense capsules, 342 Neuro-ectodermal junction, 264 Neurofibrillae, 267 Neurogens, 124 Neuroglia, 266 Neurolemma, 268 Neuromercs, 278, 281 Neurons, 267, 273 Neuropores, 109, 265 Neuro-somatic junction, 264, 269 Neurula, 7 Nipple, 373 Nissl’s granules, 267 Node or Nodes Hensen’s, 49, 389 primitive, 49, 380 of Ranvicr, 268 Non-granular leucocytes, 101 Non-rotation of intestine, 214 Norm, 125 Normoblasts, 10 1 Norrooc>'te, 101 Normogcnesis, 125 Nose, 115, 182 Nostnls, 180 Notochord, 49, 340. 385 Notochordal canal, 49

Notochordal plate, 49, 387 process, 49

Nuchal flexure, no, 271, 278 Nucleus, or Nuclei abducens, 285 acoustic, 283 ambiguus, 284 caudate, 296 cochlear, 283 cuneate, 283 dentate, 286 facial, 285

glossopharyngeal, 283 gracile, 283 habenular, 290 hypoglossal, 284 lentiform, 296 motor

of facial nerve, 285 of trigeminal nerve, 285 of vagus nerve, 285 of myelencephalon, 283 olivary, 283 of ovum, 16, 18, 37, 40 pontine, 285 pulposus, 340 red, 289

of tractus solitarius, 283, 310 trigeminal, 285 trochlear, 289 vagus, 283 vestibular, 283 Nulhparous uterus, 61 Nutrition

embryotrophic, 62 haemotrophic, 71

Oblique vein of left atrium, 168


bone, 343, 344 ganglia, 269 lobe, 280, 295 tectum, 342

Oculomotor nerve, 306, 308 Odontoblastic layer, 374 Odontoblasts, 374 Odontoid process, 339 Oesophageal arteries, 158 Oesophagus, 202, 203 Oestradiol, 17, 22 Oestrogens, 22, 90, 91 Oestrous cycle, 22, 33 Oestrus, 18, 22, 33

relation to ovulation, 18, 33 Olfactory

apparatus, 314 bulb, 279, 314 cells, 314 cortex, 298 epithehum, 314 fibres, 314 lobe, 314 nerve, 306, 314 pit, no, 114, 179, 314 placodes, 114, 182, 314 tract, 314 Oligamnios, 81

Oligodendrocytes, 266 Olivary nucleus, 283 Omental

bursa, 204, 222 superior recess, 223 Omentum

gastrohepatic, 204, 208 greater, 225 lesser, 223 Omphalopleure ' bilaminar, 393 trilaminar, 393 Ontogeny, i Oocyte

maturation of, 18 primary, 16, 19 secondary, 16, 18, 19 Oogenesis, 9, 14 Oogenetic cycle, 23 Oogonia, 15, 16 . Oophoricus, cumulus, 16 Opercula, 295 Ophthalmic nerve, 309 Optic

capsule, 344 chiasma, 282, 290, 302 cup, 278, 289, 316 disc, 320 foramen, 343 nerve, 278, 315, 317 recess, 291

stalk, 278, 281, 289, 316 sulcus, 277, 315 „ vesicle, no, 277, 289, 310 Ora serrata, 317 Oral cavity, 179, 182 Orbital muscles, 360 Orbitosphenoid, 343 Organ, or Organs absence of, 126 Chievitz’s, 188 chromaffin, 329 enamel, 374 Jacobson’s, 314 region, presumptive, 7 sense, 314 sex

accessory, i primary, i, 9 spiral, 324

supernumerary, i 2 d vomero-nasal, 314 Zuckerkandl’s, 329 Organization, 6 Organizer, 123 head, 123 mechanism, 124 primary, 123 region, 123 second grade, 123 in Siamese monsters, 131 tail, 123

third grade, 123 trunk, 123 in twins, 13 1 Organogenesis, 6

Orgasm, 39 Oro-pharynx, 201 _ Orthomesometnal implantatio

Ossicles, auditory, 326, 340 Ossific centre, 336



OssificaUon 334 centres 335 Osteoblasts 97 335 Osteoclasts 337 Osteocyte 97 33® Osteogenesis 334 Osteoid 335 Otic

capsule 344 tatvlage 324 depression 110 323 pit, 313

placode 109 277 322 \esicle no 323 Otoeyst 323 344 Ovarian cycle 23

folbcle 9 14 t6 23 pregnancy 6g Ovar

Ovary i q 14 238 anomalies of 257 258 cortex of 14 t? descent of 256 differentiation of 238 follicles of 15 16 germinal epithelium of 14 238

K ibemaculum of 256 gament of 56 medulla of 14 Pfluger I tubes of 15 stroma of 14 supernumerary ajB Oviparous 395 Ovoviviparous 393 Ovulation g 17 18 23 age 104

methods for determination of 32 multiple i3g