Difference between revisions of "McMurrich1914 Chapter 4"

From Embryology
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Froriep's Neue Notizen, xiu, 1840.) P. Thompson: "Description of a human embryo of twenty-three paired somites,"  
Froriep's Neue Notizen, xiu, 1840.) P. Thompson: "Description of a human embryo of twenty-three paired somites,"  
Journ. Anat. and Phys., xli, 1907.
Journ. Anat. and Phys., xli, 1907.
The conditions to which the embryos and larvse of the majority of animals must adapt themselves are so different from those under which the adult organisms exist that in the early stages of development special organs are very frequently developed which are of use only during the embryonic or larval period and are discarded when more advanced stages of development have been reached. This remark applies with especial force to the human embryo which leads for a period of nine months what may be termed a parasitic existence, drawing its nutrition from and yielding up its waste products to the blood of the parent. In- order that this may be accomplished certain special organs are developed by the embryo, by means of which it forms an intimate connection with the walls of the uterus, which, on its part, becomes greatly modified, the combination of embryonic and maternal structures producing what are termed the deciduce, owing to their being discarded at birth when the parasitic mode of life is given up.
Furthermore, it has already been seen that many peculiar modifications of development in the human embryo result from the inheritance of structures from more or less remote ancestors, and among the embryonic adnexes are found structures which represent in a more or less modified condition organs of considerable functional importance in lower forms. Such structures are the yolk-stalk and vesicle, the amnion, and the allantois, and for their proper understanding it will be well to consider briefly their development in some lower form, such as the chick.
At the time when the embryo of the chick begins to be constricted off from the surface of the large yolk-mass, a fold, consisting
of ectoderm and somatic mesoderm, arises just outside the embryonic area, which it completely surrounds. As development proceeds the fold becomes higher and its edges gradually draw nearer together over the dorsal surface of the embryo (Fig. 64, A, Af), and finally meet and fuse (Fig. 64, B and C), so that the embryo becomes enclosed within a sac, which is termed the amnion and is formed by the fusion of the layers which constituted the inner wall of the fold. The layers of the outer wall of the fold after fusion form part of the
Fig. 64.  -  Diagrams Illustrating the Formation of the Amnion and Allantois
in the Chick. Af, Amnion folds; Al, allantois; Am, amniotic cavity; Ds, yolk-sac.  -  (Cegenbaur.)
general ectoderm and somatic mesoderm which make up the outer wall of the ovum and together are known as the serosa, corresponding to the chorion of the mammalian embryo. The space which occurs between the amnion and the serosa is a portion of the extraembryonic ccelom and is continuous with the embryonic pleuroperitoneal cavity.
In the ovum of the chick, as in that of the reptile, the protoplasmic material is limited to one pole and rests upon the large yolk
mass. As development proceeds the germ layers gradually extend around the yolk-mass and eventually completely enclose it, the yolkmass coming to lie within the endodermal layer, which, together with the splanchnic mesoderm which lines it, forms what is termed the yolk-sac. As the embryo separates from the yolk-mass the yolksac is constricted in its proximal portion and so differentiated into a yolk-stalk and a yolk-sac, the contents of the latter being gradually absorbed by the embryo during its growth, its walls and those of the stalk being converted into a portion of the embryonic digestive tract.
In the meantime, however, from the posterior portion of the digestive tract, behind the point of attachment of the yolk-sac, a diverticulum has begun to form (Fig. 64, A, Al). This increases in size, projecting into the extra-embryonic portion of the pleuroperitoneal cavity and pushing before it the splanchnic mesoderm which lines the endoderm (Fig. 64, B and C) . This is the allantois, which, reaching a very considerable size in the chick and applying itself closely to the inside of the serosa, serves as a respiratory and excretory organ for the embryo, for which purpose its walls are richly supplied with blood-vessels, the allantoic arteries and veins.
Toward the end of the incubation period both the amnion and allantois begin to undergo retrogressive changes, and just before the hatching of the young chick they become completely dried up and closely adherent to the egg-shell, at the same time separating from their point of attachment to the body of the young chick, so that when the chick leaves the egg-shell it bursts through the driedup membranes and leaves them behind as useless structures.
The Amnion.  -  Turning now to the human embryo, it will be found that the same organs are present, though somewhat modified either in the mode or the extent of their development. A welldeveloped amnion occurs, arising, however, in a very different manner from what it does in the chick; a large yolk-sac occurs even though it contains no yolk; and an allantois which has no respiratory or excretory functions is present, though in a somewhat degenerated condition. It has been seen from the description of the earliest stages of development that the processes which occur in the lowe
forms are greatly abbreviated in the human embryo. The enveloping layer, instead of gradually extending from one pole to enclose the entire ovum, develops in situ during the stages immediately succeeding segmentation, and the extra-embryonic mesoderm, instead of growing out from the embryo to enclose the yolk-sac, splits off directly from the enveloping layer. The earliest stages in the development of the amnion are not yet known for the human embryo, but from the condition in which it is found in the Peters embryo (Fig. 37) and in the embryo v.H. of von Spee (Fig. 39) it is probable that it arises, not by the fusion of the edges of a fold, as in the chick, but by a vacuolization of a portion of the inner cellmass, as has been described as occurring in the bat (p. 54). It is, then, a closed cavity from the very beginning, the floor of the cavity being formed by the embryonic disk, its posterior wall by the anterior surface of the belly-stalk, while its roof and sides are thin and composed of a single layer of flattened ectodermal cells lined on the outside by a layer of mesoderm continuous with the somatic mesoderm of the embryo and the mesoderm of the belly-stalk (Fig. 65, A).
When the bending downward of the peripheral portions of the embryonic disk to close in the ventral surface of the embryo occurs, the line of attachment of the amnion to the disk is also carried ventrally (Fig. 65, B), so that when the constriction off of the embryo is practically completed, the amnion is attached anteriorly to the margin of the umbilicus and posteriorly to the extremity of the band of ectoderm lining what may now be considered the posterior surface of the belly-stalk, while at the sides it is attached along an oblique line joining these two points (Fig. 65, B and C, in which the attachment of the amnion is indicated by the broken line).
Leaving aside for the present the changes which occur in the attachment of the amnion to the embryo (see p. 116), it may be said that during the later growth of the embryo the amniotic cavity increases in size until finally its wall comes into contact with the chorion, the extra-embryonic body-cavity being thus practically obliterated (Fig. 65, D), though no actual fusion of amnion and
chorion occurs. Suspended by the umbilical cord, which has by this time developed, the embryo floats freely in the amniotic cavity, which is filled by a fluid, the liquor amnii, whose origin is involved in doubt, some authors maintaining that it infiltrates into the cavity from the maternal tissues, while others hold that a certain amount
Fig. 65.  -  Diagrams Illustrating the Formation of the Umbilical Cord.
The heavy black line represents the embryonic ectoderm; the dotted line represents the line of reflexion of the body ectoderm into that of the amnion. Ac, Amniotic cavity ; Al, allantois; Be, extra-embryonic ccelom; Bs, belly-stalk; Ch, chorion; P, placenta; Uc, umbilical cord; V, chorionic villi; Ys, yolk-sac.
of it at least is derived from the embryo. It is a fluid with a specific gravity of about 1.003 an( ^ contains about 1 per cent, of solids, principally albumin, grape-sugar, and urea, the last constituent probably coming from the embryo. When present in greatest quantity  -  that is to say, at about the beginning of the last month
of pregnancy  -  it varies in amount between one-half and threefourths of a liter, but during the last month it diminishes to about half that quantity. To protect the epidermis of the fetus from maceration during its prolonged immersion in the liquor amnii, the sebaceous glands of the skin at about the sixth month of development pour out upon the surface of the body a white fatty secretion known as the vernix caseosa.
During parturition the amnion, as a rule, ruptures as the result of the contraction of the uterine walls and the liquor amnii escapes as the "waters," a phenomenon which normally precedes the delivery of the child. As a rule, the rupture is sufficiently extensive to allow the passage of the child, the amnion remaining behind in the uterus, to be subsequently expelled along with the deciduae.
Occasionally it happens, however, that the amnion is sufficiently strong to withstand the pressure exerted upon it by the uterine contractions and the child is born still enveloped in the amnion, which, in such cases, is popularly known as the "caul," the possession of which, according to an old superstition, marks the child as a favorite of fortune.
As stated above, the liquor amnii varies considerably in amount in different cases, and occasionally it may be present in excessive quantities, producing a condition known as hydramnios. On the other hand, the amount may fall considerably below the normal, in which case the amnion may form abnormal unions with the embryo, sometimes producing malformations. Occasionally also bands of a fibrous character traverse the amniotic cavity and, tightening upon the embryo during its growth, may produce various malformations, such as scars, splitting of the eyelids or lips, or even amputation of a limb.
The Yolk-sac.  -  The probable mode of development of the yolk-sac in the human embryo, and its differentiation into yolk-stalk and yolk- vesicle have already been described (p. 86). When these changes have been completed, the vesicle is a small pyriform structure lying between the amnion and the chorionic mesoderm, some distance away from the extremity of the umbilical cord (Fig. 65, D), and the stalk is a long slender column of cells extending from the vesicle through the umbilical cord to unite with the intestinal tract of the embryo. The vesicle persists until birth and may be found among the decidual tissues as a small sac measuring from 3 to
10 mm. in its longest diameter. The stalk, however, early undergoes degeneration, the lumen which it at first contains becoming obliterated and its endoderm also disappearing as early as the end of the second month of development. The portion of the stalk which extends from the umbilicus to the intestine usually shares in the degeneration and disappears, but in about 3 per cent, of cases it persists, forming a more or less extensive diverticulum of the lower part of the small intestine, sometimes only half an inch or so in length and sometimes much larger. It may or may not retain connection with the abdominal wall at the umbilicus, and is known as Meckel's diverticulum.
This embryonic rudiment is of no little importance, since, when present, it is apt to undergo invagination into the lumen of the small intestine and so occlude it. How frequently this happens relatively to the occurrence of the diverticulum may be judged from the fact that out of one hundred cases of occlusion of the small intestine six were due to an invagination of the diverticulum.
In the reptiles and birds the yolk-sac is abundantly supplied with blood-vessels by means of which the absorption of the yolk is carried on, and even although the functional importance of the yolk-sac as an organ of nutrition is almost nil in the human embryo, yet it still retains a well-developed blood-supply, the walls of the vesicle, especially possessing a rich network of vessels. The future history of these vessels, which are known as the vitelline vessels, will be described later on.
The Allantois and Belly-stalk.  -  It has been seen that in reptilian and avian embryos the allantois reaches a high degree of development and functions as a respiratory and excretory organ by coming into contact with what is comparable to the chorion of the mammalian embryo. In man it is very much modified both in its mode of development and in its relations to other parts, so that its resemblance to the avian organ is somewhat obscured. The differences depend partly upon the remarkable abbreviation manifested in the early development of the human embryo and partly upon the fact that the allantois serves to place the embryo in relation with the 8
maternal blood, instead of with the external atmosphere, as is the case in the egg-laying forms. Thus, the endodermal portion of the allantois, instead of arising from the intestine and pushing before it a layer of splanchnic mesoderm to form a large sac lying freely in the extra-embryonic portion of the body-cavity, appears in the human embryo before the intestine has differentiated from the yolk-sac and pushes its way into the solid mass of mesoderm which forms the belly-stalk (Fig. 65, A). To understand the significance of this process it is necessary to recall the abbreviation in the human embryo of the development of the extra-embryonic mesoderm and body-cavity. Instead of growing out from the embryonic area, as it does in the lower forms, this mesoderm develops in situ by splitting off from the layer of enveloping cells and, furthermore, the extra-embryonic
body-cavity arises by a splitting of the mesoderm so formed before there is any trace of a splitting of the embryonic mesoderm (Fig. 38). The belly-stalk, whose development from a portion of the inner cell-mass has already been traced (p. 68), is to be regarded as a portion of the body of the embryo, since the ectoderm which covers one surface of it resembles exactly that of the embryonic disk and shows an extension backward of the medullary groove upon its surface (Fig. 66). The mesoderm, therefore, of the belly-stalk is to be regarded as a portion of the embryonic mesoderm which has not yet undergone a splitting into somatic and splanchnic layers, and, indeed, it never does undergo such a splitting, so that there is no body-cavity into which the endodermal allantoic diverticulum can grow.
But this does not account for all the peculiarities of the human allantois. In the birds, and indeed in the lower oviparous mammals, the endodermal portion of the allantois is equally developed with
Fig. 66.  -  Transverse Section THROUGH THE BELLY-STALK
of an Embryo of 2.15 mm.
Aa, Umbilical (allantoic) artery; All, allantois; am, amnion; Va, umbilical (allantoic) vein.  -  (His.)
the mesodermal portion, the allantois being an extensive sac whose cavity is rilled with fluid, and this is also true of such mammals as the marsupials, the rabbit, and the ruminants. In man, however, the endodermal diverticulum never becomes a sac-like structure, but is a slender tube extending from the intestine to the chorion and lying in the substance of the mesoderm of the belly-stalk (Fig. 65, D), the greater portion of which is to be regarded as homologous with the relatively thin layer of splanchnic mesoderm covering the endodermal diverticulum of the chick. An explanation of this disparity in the development of the mesodermal and endodermal portions of the human allantois is perhaps to be found in the altered conditions under which the respiration and secretion take place. In all forms, the lower as well as the higher, it is the mesoderm which is the more important constituent of the allantois, since in it the blood-vessels, upon whose presence the physiological functions depend, arise and are embedded. In the birds and oviparous mammals there are no means by which excreted material can be passed to the exterior of the ovum, and it is, therefore, stored up within the cavity of the allantois, the allantoic fluid containing considerable quantities of nitrogen, indicating the presence of urea. In the higher mammals the intimate relations which develop between the chorion and the uterine walls allow of the passage of excreted fluids into the maternal blood; and the more intimate these relations, the less necessity there is for an allantoic cavity in which excreted fluid may be stored up. The difference in the development of the cavity in the ruminants, for example, and man depends probably upon the greater intimacy of the union between ovum and uterus in the latter, the arrangement for the passage of the excreted material into the maternal blood being so perfect that there is practically no need for the development of an allantoic cavity.
The portion of the endodermal diverticulum which is enclosed within the umbilical cord persists until birth in a more or less rudimentary condition, but the intra-embryonic portion extending from the apex of the bladder to the umbilicus becomes converted into a solid cord of fibrous tissue termed the urachus.
Occasionally a lumen persists in the urachal portion of the allantois and may open to the exterior at the umbilicus, in which case urine from the bladder may escape at the umbilicus.
Since the allantois in the human embryo, as well as in the lower forms, is responsible for respiration and excretion, its blood-vessels are well developed. They are represented in the belly-stalk by two veins and two arteries (Fig. 66), known in human embryology as the umbilical veins and arteries. These extend from the body of the embryo out to the chorion, there branching repeatedly to enter the numerous chorionic villi by which the embryonic tissues are placed in relation with the maternal.
The Umbilical Cord.  -  During the process of closing in of the ventral surface of the embryo a stage is reached in which the embryonic and extra-embryonic portions of the body-cavity are completely separated except for a small area, the umbilicus, through which the yolk-stalk passes out (Fig. 65, B). At the edges of this area in front and at the sides the embryonic ectoderm and somatic mesoderm become continuous with the corresponding layers of the amnion, but posteriorly the line of attachment of the amnion passes up upon the sides of the belly-stalk (Fig. 65, B), so that the whole of the ventral surface of the stalk is entirely uncovered by ectoderm, this layer being limited to its dorsal surface (Fig. 66). In subsequent stages the embryonic ectoderm and somatic mesoderm at the edges of the umbilicus grow out ventrally, carrying with them the line of attachment of the amnion and forming a tube which encloses the proximal part of the yolk-stalk. The ectoderm of the belly-stalk at the same time extending more laterally, the condition represented in Fig. 65, C, is produced, and, these processes continuing, the entire belly-stalk, together with the yolk-stalk, becomes enclosed within a cylindrical cord extending from the ventral surface of the body to the chorion and forming the umbilical cord (Fig. 65, D).
From this mode of development it is evident that the cord is, strictly speaking, a portion of the embryo, its surfaces being completely covered by embryonic ectoderm, the amnion being carried
Fig. 67.  -  -Transverse Sections of the Umbilical Cord of Embryos of (A) 1.8 cm.
and (B) 25 cm. al, Allantois; c, coelom; ua, umbilical artery; uv, umbilical vein; ys, yolk-stalk.
during its formation further and further from the umbilicus until finally it is attached around the distal extremity of the cord.
In enclosing the yolk-stalk the umbilical cord encloses also a small portion of what was originally the extra-embryonic bodycavity surrounding the yolk-stalk. A section of the cord in an early stage of its development (Fig. 67, A) will show a thick mass of mesoderm occupying its dorsal region; this represents the mesoderm of the belly-stalk and contains the allantois and the umbilical arteries and vein (the two veins originally present in the belly-stalk having fused), while toward the ventral surface there will be seen a distinct cavity in which lies the yolk-stalk with its accompanying blood-vessels. The portion of this ccelom nearest the body of the embryo becomes much enlarged, and during the second month of development contains some coils of the small intestine, but later the entire cavity becomes more and more encroached upon by the growth of the mesoderm, and at about the fourth month is entirely obliterated. A section of the cord subsequent to that period of development will show a solid mass of mesoderm in which are embedded the umbilical arteries and vein, the allantois, and the rudiments of the yolk-stalk (Fig. 67, B).
When fully formed, the umbilical cord measures on the average 55 cm. in length, though it varies considerably in different cases, and has a diameter of about 1.5 cm. It presents the appearance of being spirally twisted, an appearance largely due, however, to the spiral course pursued by the umbilical arteries, though the entire cord may undergo a certain amount of torsion from the movements of the embryo in the later stages of development and may even be knotted. The greater part of its substance is formed by the mesoderm, the cells of which become stellate and form a recticulum, the meshes of which are occupied by connective-tissue fibrils and a mucous fluid which gives to the tissue a jelly-like consistence, whence it has received the name of Wharton's jelly.
The Chorion.  -  To understand the developmental changes which the chorion undergoes it will be of advantage to obtain some insight into the manner in which the ovum becomes implanted in
II 9
the wall of the uterus. Nothing is known as to how this implantation is effected in the case of the human ovum; it has already been accomplished in the youngest ovum at present known. But the process has been observed in other mammals, and what takes place in Spermophilus, for example, may be supposed to give a clue to what occurs in the human ovum. In the spermophile the ovum lies free in the uterine cavity up to a stage at which the vacuolization
* I
Fig. 68.  -  Successive Stages in the Implantation of the Ovum of the Spermophile . a, syncytial knob; k, inner cell-mass.  -  (Rejsek.)
of the central cells is almost completed (Fig. 68, A). At one region of the covering layer the cells become thicker and later form a syncytial projection or knob which comes into contact with the uterine mucosa (Fig. 68, B), and at the point of contact the mucosa cells undergo degeneration, allowing the knob to come into relation with the deeper tissues of the uterus (Fig. 68, C), the process apparently being one in which the mucosa cells are eroded by the syncytial knob. It seems probable that in the human ovum the process is at first of a similar nature and that as the covering layer cells come into
Fig. 69.  -  Diagrams Illustrating the Implantation of the Ovum. ac, amniotic cavity; bs, belly-stalk; cf, chorion frondosum; cl, chorion laeve;Jc, decidua capsularis; ic, inner cell-mass; s, space surrounding ovum which becomes the intervillous space; um, uterine mucosa; v, chorionic villus; ys, yolk-sac.
contact with the deeper layers of the uterus, these too are eroded, and, the uterine blood-vessels being included in the erosion process, an extravasation of blood plasma and corpuscles occurs in the vicinity of the burrowing ovum. In the meantime the ovum has increased considerably in size, its growth in these early stages being especially rapid, and the area of contact consequently increases in size, entailing continued erosion of the uterine mucosa. At the same time, too, the uterine tissues surrounding the ovum grow up around it, forming at first as it were a circular wall (Fig. 69, A), and eventually com
â– -K
^,^^f^>r%^^ c y
Fig. 70.  -  Section of an Ovum of i mm. A Section of the Embryo Lies in the
Lower Part of the Cavity of the Ovum.
D, Decidua; E.U., uterine epithelium; Sch, blood-clot closing the aperture left by
the sinking of the ovum into the uterine mucosa.  -  (From Strahl, after Peters.)
pletely enclose it, forming an envelope known as the decidua capsularis or rejiexa. The blood extravasation is now contained within a closed space bounded on the one hand by the uterine tissues and on the other by the wall of the ovum (Fig. 69, B).
The youngest known human ova have already reached approxi
mately this stage. Thus, the Peters ovum (Fig. 70) had already sunk deeply into the uterine mucosa, the point of entrance being indicated by a gap in the decidua capsularis, closed in this case by a patch of coagulated blood (Sch). The uterine tissues in the immediate vicinity of the ovum were much swollen and apparently somewhat necrotic and their blood-vessels could be seen to communicate with the space between the wall of the ovum and the maternal tissues. This space, however, was converted into an irregular network of blood lacunae by anastomosing cords of cells, which arose from the wall of the ovum and extended through the space to the maternal tissues ; these cords of cells are represented in Fig. 70 by the darker masses projecting from the wall of the ovum and scattered among the paler blood lacunae. This stage of implantation of the ovum is shown diagrammatically in Fig. 69, B, where, for simplicity's sake, the cell cords are represented merely as processes radiating from the ovum without reaching the maternal tissues.
The cell cords are derivatives of the trophoblast and are, therefore, of embryonic origin. If examined under a higher magnification than that shown in Fig. 70 they will be seen to be composed of an axial core of cells with distinct outlines, enclosed within a layer of protoplasm which lacks all traces of cell boundaries, although it contains numerous nuclei, being what is termed a syncytium or Plasmodium. The original trophoblast has thus become differentiated into two distinct tissues, a cellular one, which has been termed the cyto-trophoblast, and a plasmodial one, which, similarly, is known as the plasmodi-trophoblast and is the tissue that comes into contact with the maternal blood contained in the lacunar spaces and with the maternal tissues, in connection with these latter sometimes developing into masses of considerable extent. To this plasmoditrophoblast may be ascribed the active part in the destruction of the maternal tissues and probably also the absorption of the products of the destruction for the nutrition of the growing ovum. For up to this stage the ovum has been playing the role of a parasite thriving upon the tissues of^ its host.
The food material that the ovum thus obtains may conveniently
be termed the embryotroph and the type of placentation which obtains up to this stage and for some time longer may be termed the embryotrophic type. But even in the Peters ovum the preparation for another type has begun. In earlier stages the cell cords were entirely trophoblastic, but in this ovum (Fig. 70) processes from the chorionic mesoderm may be seen projecting into the bases of the cell cords, and in later stages these processes extend farther and farther into the axis of each cord, the anastomoses of the cords disappear and the cords themselves become converted into branching processes, the
Fig. 71.  -  Entire Ovum Aborted at about the Beginning of the Second Month. Xi 1/2.  -  (Grosser.)
chorionic villi, which project from the entire surface of the ovum (Fig. 71) into the surrounding space, which may now be termed the intervillous space, and are bathed by the maternal blood which it contains. Toward the maternal surface of the space some masses of the trophoblast still persist, uniting the extremities of certain of the villi to the enclosing uterine wall, such villi being termed fixation villi to distinguish them from the majority, which project freely into the intervillous space. Later, when the embryonic blood-vessels
develop, those associated with the allantois extend outward into the chorionic mesoderm and thence send branches into each villus. The second type of placentation, the hcemotrophic type, is thus established, the fetal blood contained in the vessels of the villi receiving nutrition through the walls of the villi from the maternal blood contained in the intervillous space, and, similarly, transferring waste products to it.
At first, as stated above, the villi usually cover the entire surface of the ovum, but later, as the ovum increases in size, those villi which are remote from the attachment of the belly-stalk to the chorion are placed at a disadvantage so far as their blood supply is concerned
Fig. 72.  -  Two Villi prom the Chorion of an Embryo of 7 mm.
and gradually disappear, and this process continues until, finally, only those villi are retained which are in the immediate region of the belly-stalk (Fig. 69, C), these persisting to form the fetal portion of the placenta. By these changes the chorion becomes differentiated into two regions (Fig. 69, C), one of which is destitute of villi and is termed the chorion lave, while the other provided with them, is known as the chorion frondosum.
Fig. 73.  -  Transverse Sections through Chorionic Villi in (4) the Fifth and (B) the Seventh Month of Development.
cf, Canalized fibrin; Ic, Langhans cells; s, syncytium.  -  (A which is more highly magnified than B, from Szymonowicz; B from Minot.)
Occasionally one or more patches of villi may persist in the area that normally becomes the chorion lseve and thus accessory placenta (-placenta succenturiatce) , varying in number and size, may be formed.
The villi when fully formed are processes of the chorion, branching profusely and irregularly (Fig. 72), and each consists of a core of mesoderm, containing blood-vessels, enclosed within a double layer of trophoblastic tissue (Fig. 73, A). The inner layer consists of a sheet of well defined cells arranged in a single series; it is derived from the cyto-trophoblast and forms what is known as the layer of Langhans cells. The outer layer is syncytial in structure and is formed from the plasmodi-trophoblast.
Fig. 74.  -  Mature Placenta after Separation from the Uterus. c, Cotyledons; eh, chorion, amnion, and decidua vera; urn, umbilical cord.  -  (Kollmann.)
As development proceeds the villi, which are at first distributed evenly over the chorion frondosum, become separated into groups termed cotyledons (Fig. 74) by the growth into the intervillous space of trabecular from the walls of the uterus, the fixation villi becoming connected with these septa as well as with the general uterine wall. The ectoderm of the villi also undergoes certain changes with advancing growth, the layer of Langhans cells disappearing except in small areas scattered irregularly in the villi, and the syncytium,
though persisting, undergoes local thickenings which become replaced, more or less extensively, by depositions of fibrin (Fig. 73, B, cf).
The changes which occur during the later stages of development in the chorion are very similar to those described for the villi.
Fig. 75.  -  Section through the Placental Chorion of an Embryo of Seven
Months. c, Cell layer; ep, remnants of epithelium; fb, fibrin layer; mes, mesoderm.  -  (Minot.)
Thus, the mesoderm thickens, its outermost layers becoming exceedingly fibrillar in structure, while the ectoderm differentiates into two layers, the outer of which is syncytial while the inner is cellular, and later still, as in the villi, the syncytial layer is replaced
in irregular patches by a peculiar form of fibrin which is traversed by flattened anastomosing spaces and to which the name canalized fibrin or fibrinoid has been applied (Fig. 75).
The Deciduae.  -  It has been pointed out (p. 26) that in connection with the phenomenon of menstruation periodic alterations occur in the mucous membrane of the uterus. If during one of these periods a fertilized ovum reaches the uterus, the desquamation
Fig. 76.  -  Diagram showing the Relations of the Fetal Membranes.
Am, Amnion; Ch, chorion; M, muscular wall of uterus; C, decidua capsularis; B,
decidua basalis; V, decidua vera; F, yolk-stalk.
of portions of the epithelium does not occur nor is there any appreciable hemorrhage into the cavity of the uterus; the uterine mucosa remains in what is practically the ante-menstrual condition until the conclusion of pregnancy, when, after the birth of the fetus, a considerable portion of its thickness is expelled from the uterus, forming what is termed the decidua. In other words, the sloughing of the
uterine tissue which concludes the process of menstruation is postponed until the close of pregnancy, and then takes place simultaneously over the whole extent of the uterus. Of course, the changes in the uterine tissues are somewhat more extensive during pregnancy than during menstruation, but there is an undoubted fundamental similarity in the changes during the two processes.
Fig. 77.  -  Surface View op Half of the Decldua Vera at the End of the Third
Week of Gestation.
d, Mucous membrane of the Fallopian tubes; ds, prolongation of the vera toward the
cervix uteri; pp., papillae; rf, marginal furrow. (Kollmann.)
The human ovum comes into direct apposition with only a small portion of the uterine wall, and the changes which this portion of the wall undergoes differ somewhat from those occurring elsewhere. Consequently it becomes possible to divide the deciduae into (1) a portion which is not in direct contact with the ovum, the decidua vera (Fig. 76, V) and (2) a portion which is. The latter portion is again 9
capable of division. The ovum becomes completely embedded in the mucosa, but, as has been pointed out, the chorionic villi reach their full development only over that portion of the chorion to which the belly-stalk is attached. The decidua which is in relation to this chorion frondosum undergoes much more extensive modifications than that in relation to the chorion laeve, and to it the name of decidua basalts (decidua serotina) (Fig. 76, B) is applied, while the rest of the decidua which encloses the ovum is termed the decidua capsularis (decidua rejlexa) (C).
The changes which give rise to the decidua vera may first be described and those occurring in the others considered in succession.
(a) Decidua vera.  -  On opening a uterus during the fourth or fifth month of pregnancy, when the decidua vera is at the height of its development, the surface of the mucosa presents a corrugated appearance and is traversed
Fig. 78.  -  Diagrammatic Sections of the Uterine Mucosa, A, in the Nonpregnant Uterus, and B, at the Beginning of Pregnancy. c, Stratum compactum; gl, the deepest portions of the glands; m, muscular layer; sp, stratum spongiosum.  -  (Kundrat and Engelmann.)
by irregular and rather deep grooves (Fig. 77). This appearance ceases at the internal orifice, the mucous membrane of the cervix uteri not forming a decidua, and the deciduae of the two surfaces of the uterus are separated by a distinct furrow known as the marginal groove.
In sections the mucosa is found to have become greatly thickened, frequently measuring i cm. in thickness, and its glands have undergone very considerable modification. Normally almost straight (Fig. 78, A), they increase in length, not only keeping pace with the thickening of the mucosa, but surpassing its growth, so that they become very much contorted and are, in addition, considerably dilated (Fig. 78, B). Near their mouths they are dilated, but not very much contorted, while lower down the reverse is the case, and it is possible to recognize three layers in the decidua, (1) a stratum compactum nearest the lumen of the uterus, containing the straight but dilated portions of the glands; (2) a stratum spongiosum, so called from the appearance which it presents in sections owing to the dilated and contorted portions of the glands being cut in various planes; and (3) next the muscular coat of the uterus a layer containing the contorted but not dilated extremities of the glands is found. Only in the last layer does the epithelium of the glands retain its normal columnar form; elsewhere the cells, separated from the walls of the glands, become enlarged and irregular in shape and eventually degenerate.
In addition to these changes, the epithelium of the mucosa disappears completely during the first month of pregnancy, and the tissue between the glands in the stratum compactum becomes packed with large, often multinucleated cells, which are termed the decidual cells and are probably derived from the connective tissue cells of the mucosa.
After the end of the fifth month the increasing size of the embryo and its membranes exerts a certain amount of pressure on the decidua, and it begins to diminish'in thickness. The portions of the glands which lie in the stratum compactum become more and more compressed and finally disappear, while in the spongiosum the spaces become much flattened and the vascularity of the whole decidua, at first so pronounced, diminishes greatly.
(b) Decidua capsularis.  -  The decidua capsularis has also been termed the decidua reflexa, on the supposition that it was formed as a fold of the uterine mucosa reflected over the ovum after this had
attached itself to the uterine wall. Since, however, the attachment of the ovum is to be regarded as a process of burrowing into the uterine tissues (see p. 119), the necessity for an upgrowth of a fold is limited to an elevation of the uterine tissues in the neighborhood of the ovum to keep pace with its increasing size. Since it is part of the area of contact with the ovum it possesses no epithelium upon the surface turned toward the ovum, although in the earlier stages its surface is covered by an epithelium continuous with that of the decidua vera, and between it and the chorion there is a portion of the blood extravasation in which the villi formed from the chorion laeve float. Glands and blood-vessels also occur in its walls in the earlier stages of development.
As the ovum continues to increase in size the capsularis begins to show signs of degeneration, these appearing first over the pole of the ovum opposite the point of fixation. Here, even in the case of the ovum described by Rossi Doria, the cavity of which measured 6X5 mm. in diameter, it has become reduced to a thin membrane destitute of either blood-vessels or glands, and the degeneration gradually extends throughout the entire capsule, the portion of the blood space which it encloses also disappearing. At about the fifth month the growth of the ovum has brought the capsularis in contact throughout its whole extent with the vera, and it then appears as a whitish transparent membrane with ho trace of either glands or blood-vessels, and it eventually disappears by fusing with the vera.
(c) Decidua basalis.  -  The structure of the decidua basalis, also known as the decidua serotina, is practically the same as that of the vera up to about the fifth month. It differs only in that, being part of the area of contact of the ovum, it loses its epithelium much earlier and is also the seat of extensive blood extravasations, due to the erosion of its vessels by the chorionic trophoblast. Its glands, however, undergo the same changes as those of the vera, so that in it also a compactum and a spongiosum may be recognized. Beyond the fifth month, however, there is a great difference between it and the vera, in that, being concerned with the nutrition of the embryo, it does not partake of the degeneration noticeable in the other deciduae,
but persists until birth, forming a part of the structure termed the placenta.
The Placenta.  -  This organ, which forms the connection between the embryo and the maternal tissues, is composed of two parts, separated by the intervillous space. One of these parts is of embryonic origin, being the chorion frondosum, while the other belongs to the maternal tissues and is the decidua- basalis. Hence the terms placenta fetalis and placenta uterina frequently applied to the two parts. The fully formed placenta is a more or less discoidal structure, convex on the surface next the uterine muscularis and concave on that turned toward the embryo, the umbilical cord being continuous with it near the center of the latter surface. It averages about 3.5 cm. in thickness, thinning out somewhat toward the edges, and has a diameter of 15 to 20 cm., and a weight varying between 500 and 1250 grams. It is situated on one of the surfaces of the uterus, the posterior more frequently than the anterior, and usually much nearer the fundus than the internal orifice. It develops, in fact, wherever the ovum happens to become attached to the uterine walls, and occasionally this attachment is not accomplished until the ovum has descended nearly to the internal orifice, in which case the placenta may completely close this opening and form what is termed a placenta prcevia.
If a section of a placenta in a somewhat advanced stage of development be made, the following structures may be distinguished: On the inner surface there will be a delicate layer representing the amnion (Fig. 79, Am), and next to this a somewhat thicker one which is the chorion (Cho), in which the degenerative changes already mentioned may be observed. Succeeding this comes a much broader area composed of the large intervillous blood space in which lie sections of the villi (vi) cut in various directions. Then follows the stratum compactum of the basalis, next the stratum spongiosum (Z)')> next the outermost layer of the mucosa (D"), in which the uterine glands retain their epithelium, and, finally, the muscularis uteri (Mc)
These various structures have, for the most part, been already
Fig. 79.  -  Section through a Placenta of Seven Months' Development.
Am, Amnion; cho, chorion; D, layer of decidua containing the uterine glands ;(Mc, muscular coat of the uterus; Ve, maternal blood-vessel; Vi, stalk of a villus; vi, villi in section.  -  (Minoi.)
described and it remains here only to say a few words concerning the special structure of the basal compactum and concerning certain changes that take place in the intervillous space.
The stratum compactum of the basal decidua forms what is termed the basal plate of the placenta, closing the intervillous space on the uterine side and being traversed by the maternal blood-vessels that open into the space. The formation of canalized fibrin, already mentioned in connection with the decidua vera and the syncytium of the villi, also occurs in the basal portion of the decidua, a definite layer of it, known as NitabucJi's fibrin stria, being a characteristic constituent of the basal plate and patches of greater or less extent also occur upon the surface of the plate. Leucocytes also occur in considerable abundance in the plate and their presence has been taken to indicate an attempt on the part of the maternal tissues to resist the erosive action of the parasitic ovum. From the surface of the basal plate processes, termed placental septa, project into the intervillous space, grouping the villi into cotyledons and giving attachment to some of the fixation villi (Fig. 80). Throughout the greater extent of the placenta the septa do not reach the surface of the chorion, but at the periphery, throughout a narrow zone, they do come into contact with the chorion and unite beneath it to form a membrane which has been termed the closing plate. Beneath this lies the peripheral portion of the intervillous space, which, owing to the arrangement of the septa in this region, appears to be imperfectly separated from the rest of the space and forms what is termed the marginal sinus (Fig. 80).
Attention has already been called to the formation of canalized fibrin or fibrinoid in connection with the syncytium of the villi. In the later stages of pregnancy there may be produced by this process masses of fibrinoid of considerable size, lying in the intervillous space; these, on account of their color, are termed white infarcts and may frequently be observed as whitish or grayish patches through the walls of the placenta after its expulsion. Red infarcts produced by the clotting of the blood, also occurs, but with much less regularity and frequency.
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The Separation of the Deciduae at Birth.  -  At parturition, after the rupture of the amnion and the expulsion of the fetus, there still remain in the uterine cavity the deciduae and the amnion, which is in contact but not fused with the deciduae. A continuance of the uterine contractions, producing what are termed the "after-pains," results in the separation of the placenta from the uterine walls, the separation taking place in the deep layers of the spongiosum, so that the portion of the mucosum which contains the undegenerated glands remains behind. As soon as the placenta has separated, the separation of the decidua vera takes place gradually though rapidly, the line of separation again being in the deeper layers of the stratum spongiosum, and the whole of the deciduae, together with the amnion, is expelled from the uterus, forming what is known as the "after-birth."
Hemorrhage from the uterine vessels during and after the separation of the deciduae is prevented by the contractions of the uterine walls, assisted, according to some authors, by a preliminary blocking of the mouths of the uterine vessels by certain large polynuclear decidual cells found during the later months of pregnancy in the outer layers of the decidua basalis. The regeneration of the uterine mucosa after parturition has its starting-point from the epithelium of the undegenerated glands which persist, this epithelium rapidly evolving a complete mucosa over the entire surface of the uterus.
The complicated arrangement of the human placenta is, of course, the culmination of a long series of specializations, the path along which these have proceeded being probably indicated by the conditions obtaining in some of the lower mammals. The Monotremes resemble the reptiles in being oviparous and in this group of forms there is no relation of the ovum to the maternal tissues such as occurs in the formation of a placenta. In the other mammals viviparity is the rule and this condition does demand some sort of connection between the fetal and maternal tissues. One of the simplest of such connections is that seen in the pig, where the chorionic villi of the ovum fit into corresponding depressions in the uterine mucosa, this tissue, however, undergoing no destruction, and at birth the villi simply withdraw from the depressions of the mucosa, leaving it intact. This type of placentation is an embryo trophic one, and since there is no separation of deciduae from the uterine wall after pregnancy it is also of the indeciduate type. In the sheep the placentation is
also embryotrophic and indeciduate, but destruction of the maternal mucosa does take place, the villi penetrating deeply into it and coming into relation with the connective tissue surrounding the maternal blood-vessels. Another step in advance is shown by the dog, in which even the connective tissue around the maternal vessels in the placental area undergoes almost complete destruction so that the chorionic villi are separated from the maternal blood practically only by the endothelial lining of the maternal vessels. In this case the mucosa undergoes so much alteration that the undestroyed portions if it are sloughed off after birth as a decidua, so that the placentation, like that in man, is of the deciduate type. It still represents, however, an embryotrophic type, although closely approximating to the haemotrophic one found in man, in which, as described above, the destruction of the maternal tissues proceeds so far as to open into the maternal blood-vessels, so that the fetal villi are in direct contact with the maternal blood.
If these various stages may be taken to represent steps by which the conditions obtaining in the human placenta have been evolved, the entire process may be regarded as the result of a progressive activity of a parasitic ovum. In the simplest stage the pabulum supplied by the uterus was sufficient for the nutrition of the parasite, but gradually the ovum, by means of its plasmodi-trophoblast, began to attack the tissues of its host, thus obtaining increased nutrition, until finally, breaking through into the maternal blood-vessels, it achieved for itself still more favorable nutrition, by coming into direct contact with the maternal blood.
In addition to the papers by Beneke and Strahl, Bryce and Teacher, Frassi, Jung, and Herzog, cited in Chapter III, the following may be mentioned:
E. Cova: " Ueber ein menschliches Ei der zweiten Woche," Arch, fur Gynaek., lxxxiii,
1907. L. Frassi: "Ueber ein junges menschliches Ei in situ," Arch, fiir mikr. Anal., lxx,
1907. O. Grosser: "Vergleichende Anatomic und Entwicklungsgeschichte der Eihaute
und der Placenta mit besonderer Berticksichtigung des Menschen," Wien, 1909. H. Happe: "Beobachtungen an Eihauten junger menschlicher Eier," Anat. Hefte,
xxxii, 1906. W. His: "Die Umschliessung der menschlichen Frucht wahrend der friihesten Zeit.
des Schwangerschafts," Archiv fiir Anat. und Physiol., Anat. Abth., 1897. M. Hofmeier: "Die menschliche Placenta," Wiesbaden, 1890.
F. Keibel: "Zur Entwickelungsgeschichte der Placenta," Anat. Anzeiger, iv, 1889.
J. Kollmann: "Die menschlichen Eier von 6 mm. Grosse," Archiv fiir Anat. und Physiol., Anat. Abth., 1879.
G. Leopold: "Ueber ein sehr junges menschliches Ei in situ," Arb. aus der
Frauenklinik in Dresden, rv, 1906.
F. Marchand: "Beobachtungen an jungen menschlichen Eiern," Anat.Hefte, xxi,
1903. J. Merttens: "Beitrage zur normalen und pathologischen Anatomie der mensch
lichen Placenta," Zeitschrift fiir Geburtshiilfe und Gynaekol., xxx and xxxi, 1894. C. S. Minot: "Uterus and Embryo," Journal of Morphol., n, 1889.
G. Paladino: "Sur la genese des espaces intervilleux du placenta humain et de leur
premier contenu, comparativement a la meme partie chez quelques mammiferes,"
Archives Ital. de Biolog., xxxi and xxxn, 1899. H. Peters: "Ueber die Einbettung des menschlichen Eies und das friiheste bisher
bekannte menschliche Placentationsstadium," Leipzig und Wien, 1899. J. Rejsek: "Anheftung (Implantation) des Sangetiereies an die Uteruswand, insbe
sondere des Eies von Spermophilus citellus," Arch, fiir mikrosk. Anat., lxiii, 1964. T. Rossi Doria: "Ueber die Einbettung des menschlichen Eies, studirt an einem
kleinen Eie der zweiten Woche," Arch, fiir Gynaek., lxxvi. 1905. C. Ruge: "Ueber die menschliche Placentation," Zeitschrift fur Geburtshiilfe und
Gynaekol., xxxix, 1898. Siegenbeek van Hetjkelom: "Ueber die menschliche Placentation," Arch. f. Anat.
undPhys., Anat. Abth., 1898. F. Graf Spee: "Ueber die menschliche Eikammer und Decidua reflexa," Verhandl.
des Anat. Gesellsch., xii, 1898. H. Strahl: "Die menschliche Placenta," Ergebn der Anat. und Enlwickl., II, 1893.
"Neues uber den Bau der Placenta," ibid, vi, 1897.
"Placentaranatomie," ibid., viii, 1899. R. Todyo: "Ein junges menschliches Ei," Arch, fiir Gynaek., xcv, 1912. Van Cauwenberghe : "Recherches sur la role du Syncytium dans la nutrition
embryonnaire de la femme," Arch, de Biol., xxiii, 1907. J. C. Webster: "Human Placentation," Chicago, 1901. E. Wormser: "Die Regeneration der Uterusschleimhaut nach der Geburt," Arch.
fiir Gynaek., lxix, 1903.
The Development of the Skin.  -  The skin is composed of two embryologically distinct portions, the outer epidermal layer being developed from the ectoderm, while the dermal layer is mesenchymatous in its origin.
The ectoderm covering the general surface of the body is, in the earliest stages of development, a single layer of cells, but at the end of the first month it is composed of two layers, an outer one, the epitrichium, consisting of slightly flattened cells, and a lower one whose cells are larger and which will give rise to the epidermis (Fig. 81, A). During the second month the differences between the two layers become more pronounced, the epitrichial cells assuming a characteristic domed form and becoming vesicular in structure (Fig. 81, B). These cells persist until about the sixth month of development, but after that they are cast off, and, becoming mixed with the secretion of sebaceous glands which have appeared by this time, form a constituent of the vernix caseosa.
In the meantime changes have been taking place in the epidermal layer which result in its becoming several layers thick (Fig. 81, B), the innermost layer being composed of cells rich in protoplasm, while those of the outer layers are irregular in shape and have clearer contents. As development proceeds the number of layers increases and the superficial ones, undergoing a horny degeneration, give rise to the stratum corneum, while the deeper ones become the stratum
Malpighii. At about the fourth month ridges develop on the under surface of the epidermis, projecting downward into the dermis, and later secondary ridges appear in the intervals between the primary ones, while on the palms and soles ridges appear upon the outer surface of the epidermis, corresponding in position to the primary ridges of the under surface.
The mesenchyme which gives rise to the dermis grows in from all sides between the epidermis and the outer layer of the myotomes,
Fig. 81.  -  A, Section of Skin from the Dorsum of Finger of an Embryo of 4.5 cm.;
B, from the Plantar Surface of the Foot of an Embryo of 10.2 cm
et, Epitrichium; ep, epidermis.
which are at first in contact, and forms a continuous layer underlying the epidermis and showing no indications of a segmental arrangement. It becomes converted "principally into fibrous connective tissue, the outer layers of which are relatively compact, while the deeper ones are looser, forming the subcutaneous areolar tissue. Some of the mesenchymal cells, however, become converted into non-striated muscle-fibers, which for the most part are few in number and associated with the hair follicles, though in certain regions, such as the skin of the scrotum, they are very numerous and
form a distinct layer known as the dartos. Some cells also arrange themselves in groups and undergo a fatty degeneration, well-defined masses of adipose tissue embedded in the lower layers of the dermis being thus formed at about the sixth month.
Although the dermal mesenchyme is unsegmental in character, yet the nerves which send branches to it are segmental, and it might be expected that indications of this condition would be retained by the cutaneous nerves even in the adult. A study of the cutaneous nerve-supply in the adult realizes to a very considerable extent this expectation, the areas supplied by the various nerves forming more or less distinct zones, and being therefore segmental (Fig. 82). But a considerable commingling of adjacent areas has also occurred. Thus, while the distribution of the cutaneous branches of the fourth thoracic nerve, as determined experimentally in the monkey (Macacus), is distinctly zonal or segmental, the nipple lying practically in the middle line of the zone, the upper half of its area is also supplied or overlapped by fibers of the third nerve and the lower half by fibers of the fifth (Fig. 83), so that any area of skin in the zone is innervated by fibers coming from at least two segmental nerves (Sherrington). And, furthermore, the distribution of each nerve crosses the mid-ventral line of the body, forming a more or less extensive crossed overlap.
And not only is there a confusion of adjacent areas but an area may shift its position relatively to the deeper structures supplied by the same nerve, so that the skin over a certain muscle is not necessarily supplied by fibers from the nerve which supplies the muscle. Thus, in the lower half of the abdomen, the skin at any point will be supplied by fibers from higher nerves than those supplying the underlying muscles (Sherrington), and the skin of the limbs may receive twigs from nerves which are not represented at all in the muscle-supply (second and third thoracic and third sacral).
'Ts 7i\
Fig. 82.  -  Diagram showing the cutaneOUS Distribution of the Spinal Nerves -  (Head.)
The Development of the Nails. -  The earliest indications of the development of the nails have been described by Zander in embryos of about nine weeks as slight thickenings of the epidermis
Fig. 83.  -  Diagram showing the Overlap of the III, IV, and V Intercostal Nerves of a Monkey.  -  (Sherrington.)
Fig. 84.  -  Longitudinal Section through the Terminal Joint of the IndexFinger of an Embryo of 4.5 cm. e, Epidermis; ep, epitrichium; nf, nail fold; Ph, terminal phalanx; sp, sole plate.
of the tips of the digits, these thickenings being separated from the neighboring tissue by a faint groove. Later the nail areas migrate to the dorsal surfaces of the terminal phalanges (Fig. 84) and the
grooves surrounding the areas deepen, especially at their proximal edges, where they form the nail-folds (nf) , while distally thickenings of the epidermis occur to form what have been termed sole-plates (sp), structures quite rudimentary in man, but largely developed in the lower animals, in which they form a considerable portion of the claws.
The actual nail substance does not form, however, until the embryo has reached a length of about 17 cm. By this time the epidermis has become several layers thick and its outer layers, over the nail areas as well as elsewhere, have become transformed into the stratum corneum (Fig. 85, sc), and it is in the deep layers of this (the stratum lucidum) that keratin granules develop in cells which degenerate to give rise to the nail substance (n). At its first formation, accordingly, the nail is covered by the outer layers of the stratum corneum as well as by the epitrichium, the two together forming what has been termed the eponychium (Fig. 85, ep). The epitrichium soon disappears, however, leaving only the outer layers of the stratum corneum as a covering, and this also later disappears with the exception of a narrow band surrounding the base of the nail which persists as the perionyx.
The formation of the nail begins in the more proximal portion of the nail area and its further growth is by the addition of new keratinized cells to its proximal edge and lower surface, these cells being formed only in the proximal part of the nail bed in a region marked by its whitish color and termed the lunula.
The first appearance of the nail-areas at the tips of the digits as described by Zander has not yet been
Fig. 85.  -  Longitudinal Section through the nail Area in an Embryo
OF 17 CM.
ep, Eponychium; n, nail substance; nb, nail bed; sc, stratum corneum; sp, sole plate.  -  (Okamura.)
confirmed by later observers, but the migration of the areas to the dorsal surface necessitated by such a location of the primary differentiation affords an explanation of the otherwise anomalous cutaneous nerve-supply of the nail-areas in the adult, this being from the palmar (plantar) nerves.
The Development of the Hairs.  -  The hairs begin to develop at about the third month and continue to be formed during the remaining portions of fetal life. They arise as solid cylindrical downgrowths, projecting obliquely into the subjacent dermis from
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p ...
Fig. 86.  -  The Development of a Hair. c, Cylindrical cells of stratum mucosum; hf, wall of hair follicle; m, mesoderm; mu, stratum mucosum of epidermis; p, hair papilla; r, root of hair; s, sebaceous gland.  -  (Kollmann.)
the lower surface of the epidermis. As these downgrowths continue to elongate, they assume a somewhat club-shaped form (Fig. 86, A), and later the extremity of each club moulds itself over the summit of a small papilla which develops from the dermis (Fig. 86, B). Even before the dermal papilla has made its appearance, however, a
differentiation of the cells of the downgrowth becomes evident, the central cells becoming at first spindle-shaped and then undergoing a keratinization to form the hair shaft, while the more peripheral ones assume a cuboidal form and constitute the lining of the hair follicle. The further growth of the hair takes place by the addition to its basal portion of new keratinized cells, probably produced by the multiplication of the epidermal cells which envelop the papilla.
From the cells which form the lining of each follicle an outgrowth takes place into the surrounding dermis to form a sebaceous gland, which is at first solid and club-shaped, though later it becomes lobed. The central cells of the outgrowth separate from the peripheral and from one another, and, their protoplasm undergoing a fatty degeneration, they finally pass out into the space between the follicle walls and the hair and so reach the surface, the peripheral cells later giving rise by division to new generations of central cells. During fetal life the fatty material thus poured out upon the surface of the body becomes mingled with the cast-off epitrichial cells and constitutes the white oleaginous substance, the vernix caseosa, which covers the surface of the new-born child. The muscles, arrectores pilorum, connected with the hair follicles arise from the mesenchyme cells of the surrounding dermis.
The first growth of hairs forms a dense covering over the entire surface of the fetus, the hairs which compose it being exceedingly fine and silky and constituting what is termed the lanugo. This growth is cast off soon after birth, except over the face, where it is hardly noticeable on account of its extreme fineness and lack of coloration. The coarser hairs which replace it in certain regions of the body probably arise from new follicles, since the formation of follicles takes place throughout the later periods of fetal life and possibly after birth. But even these later formed hairs do not individually persist for any great length of time, but are continually being shed, new or secondary hairs normally developing in their places. The shedding of a hair is preceded by a cessation of the proliferation of the cells covering the dermal papilla and by a shrinkage of the papilla,
whereby it becomes detached from the hair, and the replacing hair arises from a papilla which is probably budded off from the older one before its degeneration and carries with it a cap of epidermal cells.
It is uncertain whether the cases of excessive development of hair over the face and upper part of the body which occasionally occur are due to an excessive development of the later hair follicles (hypertrichosis) or to a persistence and continued growth of the lanugo.
The Development of the Sudoriparous Glands.  -  The sudoriparous glands arise during the fifth month as solid cylindrical outgrowths from the primary ridges of the epidermis (Fig. 87), and at first project vertically downward into the subjacent dermis. Later, however, the lower end of each downgrowth is thrown into coils, and at the same time a lumen appears in the center. Since, however, the cylinders are formed from the deeper layers of the epidermis, their lumina do not at first open upon the surface, but gradually approach it as the cells of the deeper layers of the epidermis replace those which are continually being cast off from the surface of the stratum corneum. The final opening to the surface occurs during the seventh month of development.
The Development of the Mammary Glands.  -  In the majority of the lower mammals a number of mammary glands occur, arranged in two longitudinal rows, and it has been observed that in the pig the first indication of their development is seen in a thickening of the epidermis along a line situated at the junction of the abdominal walls with the membrana reuniens (Schulze). This thickening subsequently becomes a pronounced ridge, the milk ridge, from which, at certain points, the mammary glands develop, the ridge
Fig. 87.  -  Lower Surface of a Detached Portion of Epidermis from the Dorsum of the Hand. h, Hair follicle; s, sudoriparous gland.  -  (Blaschko.)
disappearing in the intervals. In a human embryo 4 mm. in length an epidermal thickening has been observed which extended from just below the axilla to the inguinal region (Fig. 88) and was apparently equivalent to the milk line of the pig, and in embryos of 14 or 15 mm. the upper end of the line had become a pronounced ridge, while more posteriorly the thickening had disappeared.
The further history of the ridge has not, however, been yet traced in human embryos, and the next stage of the development of the glands which has been observed is one in which they are represented by a circular thickening of the epidermis which projects downward into the dermis (Fig. 89, A). Later the thickening becomes lobed (Fig. 89, B), and its superficial and central cells become cornified and are cast off, so that the gland area appears as a depression of the surface of the skin. During the fifth and sixth months the lobes elongate into solid cylindrical columns of cells (Fig. 90) resembling not a little the cylinders which become converted into sudoriparous glands, and each column becomes slightly enlarged at its lower end, from which outgrowths begin to develop to form the acini. A lumen first appears in the lower ends of the columns and is formed by the separation and breaking down of the central cells, the peripheral cells persisting as the lining of the acini and ducts.
The elevation of the gland area above the surface to form the nipple appears to occur at different periods in different embryos and frequently does not take place until after birth. In the region around the nipple sudoriparous and sebaceous glands develop, the latter also occurring within the nipple area and frequently opening into
Fig. 88.  -  Milk Ridge (mr) in a Human Embryo.  -  (Kallius.)
the extremities of the lacteal ducts. In the areola, as the area surrounding the nipple is termed, other glands known as Montgomery' 's glands, also appear, their development resembling that of the mammary gland so closely as to render it probable that they are really rudimentary mammary glands.
" B
Fig. 89.  -  Sections through the Epidermal Thickenings which Represent the Mammary Gland in Embryos (A) of 6 cm. and (B) or 10.2 cm.
The further development of the glands, consisting of an increase in the length of the ducts and the development from them of additional acini, continues slowly up to the time of puberty in both sexes, but at that period further growth ceases in the male, while in females it continues for a time and the subjacent dermal tissues, especially the adipose tissue, undergo a rapid development.
The occurrence of a milk ridge has not yet been observed in a sufficient number of embryos to determine whether it is a normal development or is associated with the formation of supernumerary glands (polymastia). This is by no means an infrequent anomaly; it has been observed in 19 per cent, of over 100,000 soldiers of the German army who were examined, and occurs in 47 per cent, of individuals in certain regions of Germany The extent to which the anomaly is developed varies from the occurrence of well-developed accessory glands to that of rudimentary accessory nipples (Jiy perihelia), these latter sometimes occurring in the areolar area of a normal gland and being possibly due in such cases to an hypertrophy of one or more of Montgomery's glands.
c€; * .-/'-* ., ° '>_,
Fig. 90.  -  Section through the Mammary Gland of an Embryo of 25 cm. 1, Stroma of the gland.  -  (From Nagel, after Basch.)
Although the mammary glands are typically functional only in females in the period immediately succeeding pregnancy, cases are not unknown in which the glands have been well developed and functional in males (gynecomastia). Furthermore, a functional activity of the glands normally occurs immediately after birth, infants of both sexes yielding a few drops of a milky fluid, the so-called witch-milk (Hexenmilch) , when the glands are subjected to pressure.
J. T. Bowen: "The Epitrichial Layer of the Human Epidermis," Anat. Anzeiger, rv
1889. Brouha: •' Recherches sur les diverses phases du developpement et de l'activite dela
mammelle," Arch, de Biol., xxi, 1905. G. Burckhard: "Ueber embryonale Hypermastie und Hyperthelie," Anat. Hefte
viii, 1897. H. Head: "On Disturbances of Sensation with Special Reference to the Pain of
Visceral Disease," Brain, xvi, 1892; xvn, 1894; and xix, 1896. E. Kallius: "Ein Fall von Milchleiste bei einem menschlichen Embryo," Anat.
Hefte, viii, 1897.
T. Okamura: "Ueber die Entwicklung des Nagels beim Menschen," Archiv fur
Dermatol, und Syphilol., xxv, 1900. H. Schmidt: "Ueber normale Hyperthelie menschlicher Embryonen und uber die
erste Anlage der menschlichen Milchdriisen iiberhaupt," Morphol. Arbeiten, xvil,
1897. C. S. Sherrington: "Experiments in Examination of the Peripheral Distribution of
the Fibres of the Posterior Roots of some Spinal Nerves," Philos. Trans. Royal
Soc, clxxxiv, 1893, and cxc, 1898. P. Stohr: " Entwickelungsgeschichte des menschlichen Wollhaares," Anat. Hefte,
xxiii, 1903. H. Strahl: "Die erste Entwicklung der Mammarorgane beim Menschen," Verhandl.
Anat. Gesellsch., xii, 1898.
It has been seen that the cells of a very considerable portion of the somatic and splanchnic mesoderm, as well as of parts of the mesodermic somites, become converted into mesenchyme. A very considerable portion of this becomes converted into what are termed connective or supporting tissues, characterized by consisting of a non-cellular matrix in which more or less scattered cells are embedded. These tissues enter to a greater or less extent into the formation of all the organs of the body, with the exception of those forming the central nervous system, and constitute a network which holds together and supports the elements of which the organs are composed; in addition, they take the form of definite membranes (serous membranes, fasciae), cords (tendons, ligaments), or solid masses (cartilage), or form looser masses or layers of a somewhat spongy texture (areolar tissue). The intermediate substance is somewhat varied in character, being composed sometimes of white, non-branching, non-elastic fibers, sometimes of yellow, branching, elastic fibers, of white, branching, but inelastic fibers which form a reticulum, or of a soft gelatinous substance containing considerable quantities of mucin, as in the tissue which constitutes the Whartonian jelly of the umbilical cord. Again, in cartilage the matrix is compact and homogeneous, or, in other cases, more or less fibrous, passing over into ordinary fibrous tissue, and, finally, in bone the organic matrix is largely impregnated with salts of lime.
Two views exist as to the mode of formation of the matrix, some authors maintaining that in the fibrous tissues it is produced by the actual transformation of the mesenchyme cells into fibers, while others claim that it is manufactured by the cells but does not directly
represent the cells themselves. Fibrils and material out of which fibrils could be formed have undoubtedly been observed in connective-tissue cells, but whether or not these are later passed to the exterior of the cell to form a connective-tissue fiber is not yet certain, and on this hangs mainly the difference between the theories. Recently it has been held (Mall) that the mesenchyme of the embryo is really a syncytium in and from the protoplasm of which the matrix
â– a fmm0m^&
â–  J
Fig. 91.  -  Portion of the Center of Ossification of the Parietal Bone of a
Human Embryo.
forms; if this be correct, the distinction which the older views make between the intercellular and intracellular origin of the matrix becomes of little importance.
Bone differs from the other varieties of connective tissue in that it is never a primary formation, but is always developed either in fibrous tissue or cartilage; and according as it is associated with the one or the other, it is spoken of as membrane bone or cartilage bone. In the development of membrane bone some of the connective-tissue cells, which in consequence become known as osteoblasts, deposit lime salts in the matrix in the form of bony spicules which increase in size and soon unite to form a network (Fig. 91). The trabecular of the network continue to thicken, while, at the same time, the formation of spicules extends further out into the connective-tissue membrane, radiating in all directions from the region in which it first
developed. Later the connective tissue which lies upon either surface of the reticular plate of bone thus produced condenses to form a stout membrane, the periosteum, between which and the osseous plate osteoblasts arrange themselves in a more or less definite layer and deposit upon the surface of the plate a lamella of compact bone. A membrane bone, such as one of the flat bones of the skull, thus comes to be composed of two plates of compact bone, the inner and outer tables, enclosing and united to a middle plate of spongy bone which constitutes the diploe.
With bones formed from cartilage the process is somewhat different. In the center of the cartilage the intercellular matrix becomes increased so that the cells appear to be more scattered and a calcareous deposit forms in it. All around this region of calcification the cells arrange themselves in rows (Fig. 92) and the process of calcification extends into the trabecular of matrix which separate these rows. While these processes have been taking place the mesenchyme surrounding the cartilage has become converted into a periosteum (po), similar to that of membrane bone, and its osteoblasts deposit a layer of bone (p) upon the surface of the cartilage. The cartilage cells now disappear from the intervals between the trabeculae of calcified matrix, which form a fine network into which masses of mesenchyme (Fig. 93, pi), containing blood-vessels and osteoblasts, here and there penetrate from the periosteum, after having broken through the layer of periosteal bone. These masses absorb a portion of the fine calcified network and so transform it
Fig 92.  -  Longitudinal section of Phalanx of a Finger of an Embryo of 3 1/2 Months.
c, Cartilage trabeculae; p, periosteal bone; po, periosteum; x, ossification center.  -  (Szymonowicz.)
C ^ ;
into a coarse network, the meshes of which they occupy to form the bone maigow (m), and the osteoblasts which they contain arrange themselves on the surface of the persisting trabeculse and deposit layers of bone upon their surfaces. In the meantime the calcification of the cartilage matrix has been extending, and as fast as the
network of calcified trabeculse is formed it is invaded by the mesenchyme, until finally the cartilage becomes entirely converted into a mass of spongy bone enclosed within a layer of more compact periosteal bone.
As a rule, each cartilage bone is developed from a single center of ossification, and when it is found that a bone of the skull, for instance, develops by several centers, it is to be regarded as formed by the fusion of several primarily distinct bones, a conclusion which may generally be confirmed by a comparison of the bone in question with its homologues in the lower vertebrates. Exceptions to this rule occur in bones situated in the median line of the body, these occasionally developing from two centers lying one on either side of the median line, but such centers are usually to be regarded as a double center rather than as two distinct centers, and are merely an expression of the fundamental bilaterality which exists even in median structures.
More striking exceptions are to be found in the long bones in which one or both extremities develop from special centers which give rise to the epiphyses (Fig. 94, ep, ep'), the shaft or diaphysis (d) being formed from the primary center. Similar secondary centers appear in marked prominences on bones to which powerful muscles
Fig. 93.  -  The Ossification Center of Fig. 92 More Highly Magnified. c, Ossifying trabeculse; cc, cavity of cartilage network; m, marrow cells; p, periosteal bone; pi, irruption of periosteal tissue; po, periosteum.  -  (Szymonowicz.)
are attached (Fig. 94, a and b), but these, as well as the epiphysial centers, can readily be recognized as secondary from the fact that they do not appear until much later than the primary centers of the bones to which they belong. These secondary centers give the necessary firmness required for articular surfaces and for the attachment of muscles and, at the same time, make provision for the growth in length of the bone, since a plate of cartilage always intervenes between the epiphyses and the diaphysis. This cartilage continues to be transformed into bone on both its surfaces by the extension of both the epiphysial and diaphysial ossification into it, and, at the same time, it grows in thickness with equal rapidity until the bone reaches its required length, whereupon the rapidity of the growth of the cartilage diminishes and it gradually becomes completely ossified, uniting together the epiphysis and diaphysis.
The growth in thickness of the long bones is, however, an entirely different process, and is due to the formation of new layers of periosteal bone on the outside of those already present. But in connection with this process' an absorption of bone also takes place. A section through the middle of the shaft of a humerus, for example, at an early stage of development would show a peripheral zone of compact bone surrounding a core of spongy bone, the meshes of the latter being occupied by the marrow tissue. A similar section of an adult bone, on the other hand, would show only the peripheral compact bone, much thicker than before and enclosing a large marrow cavity in which no trace of spongy bone might remain. The difference depends on the fact that as the periosteal bone
Fig. 94.  -  The Ossification Centers of the Femur.
a, and b, Secondary centers for the great and lesser trochanters; d, diaphysis; ep, upper and ep', lower epiphysis.  -  (Testut.)
increases in thickness, there is a gradual absorption of the spongy bone and also of the earlier layers of periosteal bone, this absorption being carried on by large multinucleated cells, termed osteoclasts, derived from the marrow mesenchyme. By their action the bone is enabled to reach its requisite diameter and strength, without becoming an almost solid and unwieldy mass of compact bone.
During the ossification of the cartilaginous trabeculse osteoblasts become enclosed by the bony substance, the cavities in which they lie forming the lacuna and processes radiating out from them, the
Fig. 95.  -  A, Transverse Section of the Femur of a Pig Killed after Having Been fed with Madder for Four Weeks; B, the Same of a Pig Killed Two Months after the Cessation of the Madder Feeding. The heavy black line represents the portion of bone stained by the madder.  -  (After
canaliculi, so characteristic of bone tissue. In the growth of periosteal bone not only do osteoblasts become enclosed, but bloodvessels also, the Haversian canals being formed in this way, and around these lamellae of bone are deposited by the enclosed osteoblasts to form Haversian systems.
That the absorption of periosteal bone takes place during growth can be demonstrated by taking advantage of the fact that the coloring substance madder, when consumed with food, tinges the bone being formed at the time a distinct red. In pigs fed with madder for a time and then killed a section of the femur shows a superficial band of red bone (Fig. 95, A), but if the animals be allowed to live for one or two months after the cessation of the madder feeding, the red band will be found to be covered by a layer of white bone varying in thickness according to the interval elapsed since the cessation of feeding (Fig. 95, B); and if this
interval amount to four months, it will be found that the thickness of the uncolored bone between the red bone and the marrow cavity will have greatly diminished (Flourens).
The Development of the Skeleton.  -  Embryologically considered, the skeleton is composed of two portions, the axial skeleton, consisting of the skull, the vertebrae, ribs, and sternum, developing
fin* ' \m. :
Fig. 96.  -  Frontal Section through Mesodermic Somites of a Calf Embryo.
isa, Intersegmental artery; my, myotome; n, central nervous system; nc, notochord;
sea and scp, anterior and posterior portions of sclerotomes.
from the sclerotomes of the mesodermal somites, and the appendicular skeleton, which includes the pectoral and pelvic girdles and the bones of the limbs, and which arises from the mesenchyme of the somatic mesoderm. It will be convenient to consider first the development of the axial skeleton, and of this the differentiation of the vertebral column and ribs may first be discussed.
The Development of the Vertebrae and Ribs.  -  The mesenchyme formed from the sclerotome of each mesodermic somite grows inward toward the median line and forms a mass lying between the notochord and the myotome, separated from the similar mass in front and behind by some loose tissue in which lies an intersegmental artery. Toward the end of the third week of
development the cells of the posterior portion of each sclerotome condense to a tissue more compact than that of the anterior portion (Fig. 96), and a little later the two portions become separated by a cleft. At about the same time the posterior portion sends a process medially, to enclose the notochord by uniting with a corresponding process from the sclerotome of the other side, and it also sends a prolongation dorsally between the myotome and the spinal cord to form the vertebral arch, and a third process laterally and ventrally along the distal border of the myotome to form a costal process (Fig. 97). The looser tissue of the anterior half of the sclerotome also grows medially to surround the notochord, filling up the intervals between successive denser portions, and it forms too a membrane extending between successive vertebral arches. Later the tissue surrounding the notochord, which is derived from the anterior half of the sclerotome, associates itself with the posterior portion of the preceding sclerotome to form what will later be a vertebra, the tissue occupying and adjacent to the line of division between the anterior and posterior portions of the sclerotomes condensing to form intervertebral fibrocartilages. Consequently each vertebra is formed by parts
Fig. 97.  -  Transverse Section through the intervertebral plate of the First Cervical Vertebra of a Calf Embryo of 8.8 mm.
be 1 , Intervertebral plate; m i , fourth myotome; s, hypochordal bar; XI, spinal accessory nerve.  -  (Froriep.)
from two sclerotomes, the original intersegmental artery passes over the body of a vertebra, and the vertebrae themselves alternate with the myotomes. With this differentiation the first or blastemic stage of the development of the vertebras closes.
In the second or cartilaginous stage, portions of the sclerotomic mesenchyme become transformed into cartilage. In the posterior portion of each vertebral body, that is to say in the portion formed from the anterior halves of the more posterior of the two pairs of sclerotomes entering into its formation, two centers of chondrification appear, one on each side of the median line, and these eventually unite to form a single cartilaginous body, the chondrification probably also extending to some extent into the denser anterior portion of the body. A center also appears in each half of the vertebral arch and in each costal process, the cartilages formed in the costal processes of the anterior cervical region uniting across the median line below the notochord, to form what has been termed a hypochordal bar (Figs. 97 and 98). These bars are for the most part but transitory, recalling structures occurring in the lower vertebrates; in the mammalia they degenerate before the close of the cartilaginous stage of development, except in the case of the atlas, whose development will be described later. As development proceeds the cartilages of the vertebral arches and costal processes increase in length and come into contact with the cartilaginous bodies, with which they eventually fuse, and from the vertebral arches processes grow out which represent the future transverse and articular processes.
The fusion of the cartilage of the costal process with the body of the vertebra does not, however, persist. Later a solution of the junction occurs and the process becomes a rib cartilage, the mesenchyme surrounding the area of solution forming the costo-vertebral ligaments. At first the rib cartilage is separated by a distinct interval from the transverse process of the vertebral arch, but later it develops a process, the tubercle, which bridges the gap and forms an articulation with the transverse process.
The mesenchyme which extends between successive vertebral arches does not chondrify, but later becomes transformed into the
interspinous ligaments and the ligamenta ftava, while the anterior and posterior longitudinal ligaments are formed from unchondrified portions of the tissue surrounding the vertebral bodies.
As was pointed out, the mesenchyme in the region of the cleft separating the anterior and posterior portions of a sclerotome becomes an intervertebral fibrocartilage, and, as the cartilaginous bodies develop, the portions of the notochord enclosed by them become constricted, while at the same time the portions in the intervertebral regions increase in size. Finally the notochord disappears from the vertebral regions, although a canal, representing its former position, traverses each body for a considerable time, but in the intervertebral regions it persists as relatively large flat disks forming the pulpy nuclei of the fibrocartilages.
The mode of development described above applies to the great majority of the vertebrae, but some departures from it occur, and these may be conveniently considered before passing on to an account of the ossification of the cartilages. The variations affect principally the extremes of the series. Thus the posterior vertebrae present a reduction of the vertebral arches, those of the last sacral vertebrae being but feebly developed, while in the coccygeal vertebrae they are indicated only in the first. In the first cervical vertebra, the atlas, the reverse is the case, for the entire adult vertebra is formed from the posterior portion of a sclerotome, its lateral masses and posterior arch being the vertebral arches, while its anterior arch is the hypochordal bar, which persists in this vertebra only. A welldeveloped centrum is also formed, however (Fig. 98), but it does not unite with the parts derived from the preceding sclerotome, but during its ossification unites with the centrum of the epistropheus (axis), forming the odontoid process of that vertebra. The epistropheus consequently is formed by one and a half sclerotomes, while but half a one constitutes the atlas.
The extent to which the ribs are developed in connection with the various vertebrae also varies considerably. Throughout the cervical region they are short, the upper five or six being no longer than the transverse processes, with the tips of which their extremities
unite at an early stage. In the upper five or six vertebrae a relatively large interval persists between the rib and the transverse process, forming the costo-transverse foramen, through which the vertebral vessels pass, but in the seventh vertebra the fusion is more extensive and the foramen is very small and hardly noticeable. In the thoracic region the ribs reach their greatest development, the upper eight or
â–  \;-^Z ... --â– 
Fig. 9,8.  -  Longitudinal Section through the Occipital Region and Upper
Cervical Vertebrae of a Calf Embryo of 18.5 mm.
has, Basilar artery; ch, notochord; Kc l ~ 4 , vertebral centra; lc 2 ~ 4 , intervertebral
disks; occ, basioccipital; Sc x ~ 4 , hypochordal bars.  -  (Froriep.)
nine extending almost to the mid-ventral line, where their extremities unite to form a longitudinal cartilaginous bar from which the sternum develops (see p. 166). The lower three or four thoracic ribs are successively shorter, however, and lead to the condition found in the lumbar vertebras, where they are again greatly reduced and firmly united with the transverse processes, the union being so close that only the tips of the latter can be distinguished, forming what are known as the accessory tubercles. In the sacral region the ribs
are reduced to short flat plates, which unite together to form the lateral masses of the sacrum, and, finally, in the coccygeal region the blastemic costal processes of the first vertebra unite with the transverse processes to form the transverse processes of the adult vertebra, but no indications of them are to be found in the other vertebrae beyond the blastemic stage.
The third stage in the development of the axial skeleton begins with the ossification of the cartilages, and in each vertebra there are typically as many primary centers of ossification as there were originally cartilages, except that but a single center appears in the body. Thus, to take a thoracic vertebra as a type, a center appears in each half of each vertebral arch at the base of the transverse process and gradually extends to form the bony lamina, pedicle, and the greater portion of the transverse and spinous processes; a single center gives rise to the body of the vertebra; and each rib ossifies
Fig. 99.  -  A, A Vertebra at Birth; B, Lumbar Vertebra showing Secondary Centers of Ossification. a, Center for the articular process; c, body; el, lower epiphysial plate; en, upper epiphysial plate; na, vertebral arch; s, center for spinous process; t, center for transverse process.  -  (Sappey.)
from a single center. These various centers appear early in embryonic life, but the complete transformation of the cartilages into bone does not occur until some time after birth, each vertebra at that period consisting of three parts, a body and two halves of an arch, separated by unossified cartilage (Fig. 99, A). At about puberty secondary centers make their appearance; one appears in the cartilage which still covers the anterior and posterior surfaces of the vertebral body, producing disks of bone in these situations (Fig. 99,
l6 5
B, en and el), another appears at the tip of each spinous and transverse process (Fig. 99, B), and in the lumbar vertebrae others appear at the tips of the articulating processes. The epiphyses so formed remain separate until growth is completed and between the sixteenth and twenty-fifth years unite with the bones formed from the primary centers, which have fused by this time, to form a single vertebra.
Each rib ossifies from a single primary center situated near the angle, secondary centers appearing for the capitulum and tuberosity.
In some of the vertebras modifications of this typical mode of ossification occur. Thus, in the upper five cervical vertebrae the centers for the rudimentary ribs are suppressed, ossification extending into them from the vertebral arch centers, and a similar suppression of the costal centers occurs in the lower lumbar vertebrae, the first only developing a separate rib center. Furthermore, in the
Fig. ioo. - A, Upper Surface of the First Sacral Vertebra, and B, Ventral
View of the Sacrum showing Primary Centers of Ossification.
c, Body; na, vertebral arch; r, rib center.  -  (Sappey.)
atlas a double center appears in the persisting hypochordal bar, and the body which corresponds to the atlas, after developing the terminal epiphysial disks, fuses with the body of the epistropheus (axis) to form its odontoid process, this vertebra consequently possessing, in addition to the typical centers, one (double) other primary and two secondary centers. In the sacral region the typical centers appear
in all five vertebrae, with the exception of rib centers for the last one or two (Fig. ioo) and two additional secondary centers give rise to plate-like epiphyses on each side, the upper plates forming the articular surface for the ilium. At about the twenty-fifth year all the sacral vertebrae unite to form a single bone, and a similar fusion occurs also in the rudimentary vertebrae of the coccyx.
The majority of the anomalies seen in the vertebral column are due to the imperfect development of one or more cartilages or of the centers of ossification. Thus, a failure of an arch to unite with the body or even the complete absence of an arch or half an arch may occur, and in cases of spina bifida the two halves of the arches fail to unite dorsally. Occasionally the two parts of the double cartilaginous center for the body fail to unite, a double body resulting; or one of the two parts may entirely fail, the result being the formation of only one-half of the body of the vertebra. Other anomalies result from the excessive development of parts. Thus, the rib of the seventh cervical vertebra may sometimes remain distinct and be long enough to reach the sternum, and the first lumbar rib may also fail to unite with Its vertebra. On the other hand, the first thoracic rib is occasionally found to be imperfect.
The Development of the Sternum.  -  Longitudinal bars, which are formed by the fusion of the ventral ends of the anterior eight or nine cartilaginous thoracic ribs, represent the future sternum. At an early period the two bars come into contact anteriorly and fuse together (Fig. 101), and at this anterior end two usually indistinctly separated masses of cartilage are to be observed at the vicinity of the points where the ventral ends of the cartilaginous clavicles articulate. These are the episternal cartilages (em), which later normally unite with the longitudinal bars and form part of the manubrium sterni, though occasionally they persist and ossify to form the ossa suprasternal. The fusion of the longitudinal bars gradually extends backward until a single elongated plate of cartilage results, with which the seven anterior ribs are united, one or two of the more posterior ribs which originally took part in the formation of each bar having separated. The portions of the bars formed by these posterior ribs constitute the xiphoid process.
The ossification of the sternum (Fig. 102) partakes to a certain extent of the original bilateral segmental origin of the cartilage,
but there is a marked condensation of the centers of ossification and considerable variation in their number also occurs. In the portion of the cartilage which lies below the junction of the third costal cartilages a series of pairs of centers appears just about birth, each center
Fig. ioi.  -  Formation of the Sternum in an Embryo of About 3 cm. el, Clavicle; em, episternal cartilage.  -  (Ruge.)
probably representing an epiphysial center of a corresponding rib. Later the centers of each pair fuse and the single centers so formed, extending through the cartilage, eventually unite to form the greater part of the body of the bone. In each of the two uppermost segments, however, but a single center appears, that of the second segment uniting with the more posterior centers and forming the upper part of the body, while the uppermost center gives rise to the manubrium, which frequently persists as a distinct bone united to the body by a hinge-joint.
A failure of the cartilaginous bars to fuse produces the condition known as cleft sternum, or if the failure to fuse affects only a portion of the bars there results a perforated sternum. A perforation or notching of the xiphoid cartilage is of frequent occurrence owing to this being the region where the fusion of the bars takes place last.
Fig. i 02.  -  Sternum of New-born Child, showing Centers of Ossification. I to VII, Costal cartilages.  -  (Gegenbaur.)
Fig. 103.  -  Reconstruction of the Chondrocranium of an embryo of 14 mm. as, Alisphenoid; bo, basioccipital; bs, basisphenoid; eo, exoccipital; m, Meckel's cartilage; os, orbitosphenoid; p, periotic; ps, presphenoid; so, sella turcica; s, supraoccipital.  -  (Levi.)
The suprasternal bones are the rudiments of a bone or cartilage, the omosternum, situated in front of the manubrium in many of the lower mammalia. It furnishes the articular surfaces for the clavicles and is possibly formed by a fusion of the ventral ends of the cartilages which represent those bones; hence its appearance as a pair of bones in the rudimentary condition.
The Development of the Skull.  -  In its earliest stages the human skull is represented by a continuous mass of mesenchyme which invests the anterior portion of the notochord and extends forward beyond its extremity into the nasal region, forming a core for the nasal process (see p. 99). From each side of this basal mass a wing projects dorsally to enclose the anterior portion of the medullary canal which will later become the cerebral part of the central nervous system. No indications of a segmental origin are to be
found in this mesenchyme; as stated, it is a continuous mass, and this is likewise true of the cartilage which later develops in it.
The chondrihcation occurs first along the median line in what will be the occipital and sphenoidal regions of the skull (Fig. 103) and thence gradually extends forward into the ethmoidal region and to a certain extent dorsally at the sides and behind into the regions later occupied by the wings of the sphenoid (as and os) and the squamous portion of the occipital (s). No cartilage develops, however, in the rest of the sides or in the roof of the skull, but the mesenchyme of these regions becomes converted into a dense membrane of connective tissue. While the chondrification is proceeding in the regions mentioned, the mesenchyme which encloses the internal ear becomes converted into cartilage, forming a mass, the periotic capsule (Fig. 103, p), wedged in on either side between the occipital and sphenoidal regions, with which it eventually unites to form a continuous chondro cranium, perforated by foramina for the passage of nerves and vessels.
The posterior part of the basilar portion of the occipital cartilage presents certain peculiarities of development. In calf embryos there are in this region, in very early stages, four separate condensations of mesoderm corresponding to as many mesodermic somites and to the three roots of the hypoglossal nerve together with the first cervical or suboccipital nerve (Froriep) (Fig. 104). These mesenchymal masses in their general characters and relations resemble vertebral bodies, and there are good reasons for believing that they represent four vertebrae which, in later stages, are taken up into the skull region and fuse with the primitive chondrocranium. In the human embfyo they are less distinct than in lower mammals, but since a three-rooted hypoglossal and a suboccipital nerve also occur in man it is probable that the corresponding vertebrae are also represented. Indeed, confirmation of their existence may be found in the fact that during the cartilaginous stage of the skull the hypoglossal foramina are divided into three portions by two cartilaginous partitions which separate the three roots of the hypoglossal nerve. It seems certain from the evidence derived from embryology and comparative
anatomy that the human skull is composed of a primitive unsegmental chondrocranium plus four vertebrae, the latter being added
to and incorporated with the occipital portion of the chondrocranium. Emphasis must be laid upon the fact that the cartilaginous portion of the skull forms only the base and lower portions of the sides of the cranium, its entire roof, as well as the face region, showing no indication of cartilage, the mesenchyme in these regions being converted into fibrous connective tissue, which, especially in the cranial region, assumes the form of a dense membrane.
But in addition to the chondrocranium and the vertebras incorporated with it, other cartilaginous elements enter into the composition of the skull. The mesenchyme which occupies the axis of each branchial arch undergoes more or less complete chondrification, cartilaginous bars being so formed, certain of which enter into very close relations with the skull. It has been seen (p. 92) that each half of the first arch gives rise to a maxillary process which grows forward and ventrally to form the anterior boundary of the mouth, while the remaining portion of the arch forms the mandibular process. The whole of the axis of the mandib
J-^V : y:
Fig. 104.  -  Frontal Section through the occipital and upper Cervical Regions of a Calf Embryo of 8.7 MM.
ai and ai 1 , Intervertebral arteries; be 1 , first cervical intervertebral plate; bo, suboccipital intervertebral plate; c 1 -  2 , cervical nerves; eh, notochord; K, vertebral centrum; m l  -  3 , occipital myotomes; m 4 -  5 , cervical myotomes; 1 -  3 , roots of hypoglossal nerve; vj, jugular vein; x and xi, vagus and spinal accessory nerves.  -  (Froriep.)
ular process becomes chondrified, forming a rod known as Meckel's cartilage, and this, at its dorsal end, comes into relation with the periotic capsule, as does also the dorsal end of the cartilage of the second arch. In the remaining three arches cartilage forms only in the ventral portions, so that their rods do not come into relation with the skull, though it will be convenient to consider their further history together with that of the other branchial arch cartilages. The arrangement of these cartilages is shown diagrammatically in Fig. 105.
By the ossification of these various parts three categories of bones are formed: (1) cartilage bones formed in the chondrocranium, (2) membrane bones, and (3) cartilage bones developing from the cartilages of the branchial arches. The bones belonging to each of these categories are primarily quite distinct from one another and from those of the other groups, but in the human skull a very considerable amount of fusion of the primary bones takes place, and elements belonging to two or even to all three categories may unite to form a single bone of the adult skull. In a certain region of the chondrocranium also and in one of the branchial arches the original cartilage bone becomes ensheathed by membrane bone and eventually disappears completely, so that the adult bone, although represented by a cartilage, is really a membrane bone. And, indeed, this process has proceeded so far in certain portions of the branchial arch skeleton that the original cartilaginous representatives are no longer developed, but the bones are deposited directly in connective tissue. These various modifications interfere greatly with the precise application to the human skull of the classification of bones into the three categories given above, and indeed the true significance of certain of the skull bones can only be perceived by comparative
Fig. 105.  -  Diagram showing the Five
Branchial Cartilages, I to'F.
At, Atlas; Ax, epistropheus; 3, third
cervical vertebra.
studies. Nevertheless it seems advisable to retain the classification, indicating, where necessary, the confusion of bones of the various categories.
The Ossification of the Chondrocranium.  -  The ossification of the cartilage of the occipital region results in the formation of four distinct bones which even at birth are separated from one
another by bands of cartilage. The portion of cartilage lying in front of the foramen magnum ossifies to form a basioccipital bone (Fig. 106, bo), the portions on either side of this give rise to the two exoccipitals (eo), which bear the condyles, and the portion above the foramen produces a supraoccipital (so), which represents the part of the squamous portion of the adult bone lying below the superior nuchal line. All that portion of the bone which lies above that line is composed of membrane bone which owes its origin to the fusion of two or sometimes four centers of ossification, appearing in the membranous roof of the embryonic skull. The bone so formed (ip) represents the interparietal of lower vertebrates and, at an early stage, unites with the supraoccipital, although even at birth an indication of the line of union of the two parts is to be seen in two deep incisions at the sides of the bone. The union of the exoccipitals and supraoccipital takes place in the course of the first or second year after birth, but the basioccipital does not fuse with the rest of the bone until the sixth or eighth year. It will be noticed that no special centers occur for the four occipital vertebrae, these structures having become completely incorporated in the chondro
Fig. 106.  -  Occipital Bone of a Fetus
at Term. bo, Basioccipital; eo, exoccipital; ip, interparietal; so, supraoccipital.
cranium, and even the cartilaginous partitions which divide the hypoglossal foramina usually disappear during the process of ossification.
Two pairs of centers have been described for the interparietal bone and it has been claimed that the deep lateral incisions divide the lower pair, so that when the incisions meet and persist as the sutura mendosa, separating the so-called inca bone from the rest of the occipital, the division does not correspond to the line between the supraoccipital and the interparietal, but a portion of the latter bone remains in connection with the supraoccipital. Mall, however, in twenty preparations, found but a single pair of centers for the interparietal.
Occasionally an additional pair of small centers appear for the uppermost angle of the interparietal, and the bones formed from them may remain distinct as what have been termed fontanelle bones.
Fig. 107.  -  Sphenoid Bone from Embryo of 3^ to 4 Months. The parts which are still cartilaginous are represented in black, as, Alisphenoid ; b, basisphenoid; /, lingula; os, orbitosphenoid ; p, internal pterygoid plate.  -  (Sappey.)
In the sphenoidal region the number of distinct bones which develop is much greater than in the occipital region. At the beginning of the second month a center appears in each of the cartilages which represent the alisphenoids (great wings). These cartilages do not, however, represent the entire extent of the great wings and their ossification gives rise only to those portions of the bone in the neighborhood of the foramina ovale and rotundum and to the lateral pterygoid plates. The remaining portions of the wings, the orbital and temporal portions, develop as membrane bone (Fawcett)
and early unite with the portions formed from the cartilage. At the end of the second month a center appears in each orbito sphenoid (lesser wing) cartilage (Fig. 107, os), and a little later a pair of centers (b), placed side by side, are developed in the cartilage representing the posterior portion of the body; together these form what is known as the basisphenoid. Still later a center appears on either side of the basisphenoids to form the UngulcB (I), and another pair appears in the anterior part of the cartilage, between the orbitosphenoids, and represent the presphenoid.
In addition to these ten centers in cartilage and the membrane portion of the alisphenoid, two other membrane bones are included in the adult sphenoid. Thus, a little before the appearance of the center for the alisphenoids an ossification is formed in the mesenchyme of each lateral wall of the posterior part of the nasal cavity and gives rise to the medial lamina of the pterygoid process, the mesenchyme at the tip of the ossification condensing to form a cartilaginous hook-like structure over which the tendon of the tensor veli palatini plays. This cartilage later ossifies to form the pterygoid hamulus, the medial pterygoid lamina being thus a combination of membrane and cartilage, the latter, however, being a secondary development and quite independent of the chondrocranium.
By the sixth month the lingular have fused with the basisphenoid and the orbitosphenoids with the presphenoid, and a little later the basisphenoid and presphenoid unite. The alisphenoids and medial pterygoid laminae remain separate, however, until after birth, fusing with the remaining portions of the adult bone during the first year.
The cartilage of the ethmoidal region of the chondrocranium forms somewhat later than the other portions and consists at first of a stout median mass projecting downward and forward into the nasal process (Fig. 108, Ip), and two lateral masses (lm), situated one on either side in the mesenchyme on the outer side of each olfactory pit. Ossification of the lateral masses or ectethmoids begins relatively early, but it appears in the upper part of the median cartilage only after birth, producing the crista galli and the perpendicular plate, which together form what is termed the mesethmoid. When
first formed, the three cartilages are quite separate from one another, the olfactory and nasal nerves passing down between them to the olfactory pit, but later trabecular begin to extend across from the mesethmoid to the upper part of the ectethmoids and eventually form a fenestrated horizontal lamella which ossifies to form the cribriform plate.
The lower part of the median cartilage does not ossify, but a center appears on each side of the median line in the mesenchyme behind and below its posterior or lower border. From these centers two vertical bony plates develop which unite by their median surfaces below, and above invest the lower border of the cartilage and form the vomer. The portion of the cartilage which is thus invested undergoes resorption, but the more anterior portions persist to form the cartilaginous septum of the nose. The vomer, consequently, is not really a portion of the chondrocranium, but is a membrane bone; its intimate relations with the median ethmoidal cartilage, however, make it convenient to consider it in this place.
When first formed, the ectethmoids are masses of spongy bone and show no indication of the honeycombed appearance which they present in the adult skull. This condition is produced by the absorption of the bone of each mass by evaginations into it of the mucous membrane lining the nasal cavity. This same process also brings about the formation of the curved plates of bone which project from the inner surfaces of the lateral masses and are known as the superior and middle conchse (turbinated bones). The inferior and sphenoidal conchae are developed from special centers, but belong to the same category as the others, being formed from portions of the lateral ethmoidal cartilages which become almost
Fig. 108.  -  Anterior Portion of the Base of the Skull of a 6 to 7 Months' Embryo.
The shaded parts represent cartilage. cp, Cribriform plate; hn, lateral mass of the ethmoid; Ip, perpendicular plate; of optic foramen; os, orbitosphenoid.  -  (After von Spec.)
separated at an early stage before the ossification has made much progress. Absorption of the body of the sphenoid bone to form the sphenoidal cells, of the frontal to form the frontal sinuses, and of the maxillaries to form the maxillary antra is also produced by outgrowths of the nasal mucous membrane, all these cavities, as well as the ethmoidal cells, being continuous with the nasal cavities and lined with an epithelium which is continuous with the mucous membrane of the nose.
In the lower mammalia the erosion of the mesial surface of the ectethmoidal cartilages results, as a rule, in the formation of five conchae, while in man but three are usually recognized. Not infrequently, however, the human middle concha shows indications, more or less marked, of a division into an upper and a lower portion, which correspond to the third and fourth bones of the typical mammalian arrangement. Furthermore, at the upper portion of the nasal wall, in front of
the superior concha, a slight elevation, termed the agger nasi, is always observable, its lower edge being prolonged downward to form what is termed the uncinate process of the ethmoid. This process and the agger together represent the uppermost concha of the typical arrangement, to which, therefore, the human arrangement may be reduced.
A number of centers of ossification  -  the exact number is yet uncertain  -  appear in the periotic capsule during the later portions of the fifth month, and during the sixth month these unite together to form a single center from which the complete ossification of the cartilage proceeds to form the petrous and mastoid portions of the temporal bone (Fig. 109, p). The mastoid process does not really form until several years after birth, being produced by the hollowing and bulging out of a portion of the petrous bone by out-growths from the lining membrane of the middle ear. The cavities so formed are the mastoid cells, and their relations to the middle-ear cavity are in all respects similar to those of the ethmoidal
Fig. 109.  -  The Temporal
Bone at Birth. The Styloid
Process and Auditory Ossicles
are not Represented.
p, Petrous bone; s, squamosal;
t, tympanic.  -  (Poirier.)
and sphenoidal cells to the nasal cavities. The remaining portions of the temporal bone are partly formed by membrane bone and partly from the branchial arch skeleton. An ossification appears at the close of the eighth week in the membrane which forms the side of the skull in the temporal region and gives rise to a squamosal bone (s), which later unites with the petrous to form the squamosal portion of the adult temporal, and another membrane bone, the tympanic (/), develops from a center appearing in the mesenchyme surrounding the external auditory meatus, and later also fuses with the petrous to form the floor and sides of the external meatus, giving attachment at its inner edge to the tympanic membrane. Finally, the styloid process is developed from the upper part of the second branchial arch, whose history will be considered later.
The various ossifications which form in the chondrocranium and the portions of the adult skull which represent them are shown in the following table:
Region of Chondrocranium.
IBasioccipital Exoccipitals Supraoccipital
Ethmoidal .
Parts of Adult Skull;
Basilar process. Condyles.
Squamous portion below superior nuchal line.
Greater wings (in part) . Lesser wings. Lamina perpendicularis. Crista galli. Nasal septum. Lateral masses. Superior concha. Middle concha.
Inferior concha.
Sphenoidal concha.
,, . . f Mastoid.
Penolic capsule < _.
1 Petrous.
The Membrane Bones of the Skull. -  In the membrane forming the sides and roof of the skull in the second stage of its develop
ment ossifications appear, which give rise, in addition to the interparietal and squamosal bones already mentioned in connection with the occipital and temporal, to the parietals and frontal. Each of the former bones develops from a single center which appears at the end of the eighth week, while the frontal is formed at about the same time from two centers situated symmetrically on each side of the median line and eventually fusing completely to form a single bone, although more or less distinct indications of a median suture, the metopic, are not infrequently present.
Furthermore, ossifications appear in the mesenchyme of the facial region to form the nasal, lachrymal, and zygomatic bones, all of which arise from single centers of ossification. In the case of each zygomatic bone, however, three osseous thickenings appear on the inner surface of the original ossification, which then disappears and the thickenings unite to form the adult bone, though occasionally one or more of their lines of union may persist, producing a bipartite or tripartite zygomatic.
The vomer, which has already been described, belongs also strictly to the category of membrane bones, as do also the maxillae and the palatines; these latter, however, primarily belonging to the branchial arch skeleton, with which they will be considered.
The purely membrane bones in the skull, are, then, the following:
Interparietals Part of squamous portion of occipital.
Pterygoids Medial pterygoid plates.
Squamosals Squamous portions of temporals.
Tympanies Tympanic plates of temporals.
The Ossification of the Branchial Arch Skeleton.  -  It has
been seen (p. 171) that a cartilaginous bar develops only in the mandibular process of the first branchial arch. In the maxillary process no cartilaginous skeleton forms, but two membrane bones,
Fig. i 10.  -  Diagram of the Ossifications of which the Maxilla is Composed, as seen from the Outer Surface. The Arrow Passes through the Infraorbital Canal.  -  (From von Spee, after Sappey.)
the palatine and maxilla, are developed in it, their cartilaginous representatives, which are to be found in lower vertebrates, having been suppressed by a condensation of the development. The palatine bone develops from a single center of ossification, but for each maxilla no less than five centers have been described (Fig. no). One of these gives rise to so much of the alveolar border of the bone as contains the bicuspid and molar teeth; a second forms the nasal process and the part of the alveolar border which contains the canine tooth; a third the portion which contains the incisor teeth; while the fourth and fifth centers lie above the first and give rise to the inner and outer portions of the orbital plate and the body of the bone. The first, second, fourth, and fifth portions early unite together, but the third center, which really lies in the ventral part of the nasal process, remains separate for some time, forming what is termed the premaxilla, a bone which remains permanently distinct in the majority of the lower mammals.
The above is the generally accepted view as to the development of the maxilla. Mall, however, maintains^ that it has but tw r o centers of ossification, one giving rise to the premaxilla and the other to the rest of the bone. The maxillary center makes its appearance about the middle of the sixth week.
Since the condition known as hare-lip results from a failure of the maxillary process to unite completely with the frontonasal process (see p. 100), and since the premaxilla develops in the latter and the maxilla in the former, the cleft may pass between these two bones and prevent their union (see also p. 284).
The upper end of Meckel's cartilage passes between the tympanic bone and the outer surface of the periotic capsule and thus comes to lie apparently within the tympanic cavity of the ear; this portion of the cartilage divides into two parts which ossify to form two of the bones of the middle ear, the malleus and incus, a description of
whose further development may be postponed until a later chapter. At about the middle of the sixth week of development a plate of membrane bone appears to the outer side of the lower portion of the cartilage and gradually extends to form the body and ramus of the mandible.
In the region of the body the bone develops so as to enclose the cartilage, together with the inferior alveolar (dental) nerve which lies to the outer side of the cartilage, but in the region of the ramus
Fig. hi. -  Model of Right Half of Mandible of a Fetus 95 mm. in Length, seen from the mesial surface. C 1 and C 2 , Accessory cartilages; Ch. T., chorda tympanijO., cartilage for coronoid process; Cy., cartilage for condyloid process; Mai., malleus; M.C., Meckel's cartilage; N. Al., inferior alveolar nerve; N. Aur., auriculo-temporal nerve; N.L., lingual nerve; N.Mh., mylo-hyoid nerve; N.T., trigeminal nerve; Sy., symphysis.  -  (Low.)
the bone remains entirely to the outer side of the cartilage and nerve, whence the position of the mandibular foramen on the inner surface of the adult bone. The anterior portion of Meckel's cartilage becomes ossified by the extension of ossification from the membrane bone into it, the portion corresponding to the body of the bone behind the mental foramen disappears and the portion above the mandibular foramen is said to become transformed into fibrous connective tissue and to persist as the spheno-mandibular ligament. At the upper extremity of the ramus two nodules of cartilage develop, quite independently, however, of Meckel's cartilage (Fig. in, Cr and Cy),
and ossification extends into these from the ramus to form the coronoid and condyloid processes. And, finally, two other independent cartilages appear toward the anterior extremity of each half
Fig. 112.  -  Diagram showing the Categories to which the Bones of the Skull . . Belong.
The unshaded bones are membrane bones, the heavily shaded represent the chondrocranium, while the black represents the branchial arch elements. AS, Alisphenoid; ExO, exoccipital; F, frontal; Hy, hyoid; IP, interparietal; Z, zygomatic; Mn, mandible; Mx, maxilla; NA, nasal; P, parietal; Pe, periotic; SO, supraoccipital; Sg, squamosal; St, styloid process; Th, thyreoid cartilage; Ty, tympanic.
of the bone, one at the alveolar (C t ) and the other at the lower border (C 2 ), and these, also are later incorporated into the bone without developing special centers of ossification.
Each half of the mandible thus ossifies from a single center, and is essentially a membrane bone replacing a cartilaginous precursor. At birth the two halves are united at the symphysis by fibrous tissue, into which ossification extends later, union occurring in the first or second year.
The upper part of the cartilage of the second branchial arch also comes into relation with the tympanic cavity and ossifies to form the styloid process of the temporal bone. The succeeding moiety of the cartilage undergoes degeneration to form the stylo-hyoid ligament, while its most ventral portion ossifies as the lesser comu of trie hyoid bone. The great variability which may be observed in the length of the styloid processes and of the lesser cornua of the hyoid depends upon the extent to which the ossification of the original cartilage proceeds, the length of the stylo-hyoid ligaments being in inverse ratio to the length of the processes or cornua. The greater cornua of the hyoid are formed by the ossification of the cartilages of the third arch, and the body of the bone is formed from a cartilaginous plate, the copula, which unites the ventral ends of the two arches concerned.
Finally, the cartilages of the fourth and fifth branchial arches early fuse together to form a plate of cartilage, and the two plates of opposite sides unite by their ventral edges to form the thyreoid cartilage of the larynx.
The accompanying diagram (Fig. 112) shows the various structures derived from the branchial arch skeleton, as well as some of the other elements of the skull, and a re'sume' of the fate of the branchial arches may be stated in tabular form as follows, the parts represented by cartilage which becomes replaced by membrane bone being printed in italics, while membrane bones which have no cartilaginous representatives are enclosed in brackets:
(Palatine) .
Spheno-mandibular ligament.
1st arch.
(Styloid process of the temporal. Stylo-hyoid ligament. Lesser cornu of hyoi< 1 .
3d arch Greater cornu of hyoid.
4th and 5th arches Thyreoid cartilage of larynx.
The Development of the Appendicular Skeleton.  -  While the greater portion of the axial skeleton is formed from the sclerotomes of the mesodermic somites, the appendicular skeleton is derived from the somatic mesenchyme, which is not divided into metameres. This mesenchyme forms the core of the limb bud and becomes converted into cartilage, by the ossification of which all the bones of the limbs, with the possible exception of the clavicle, are formed.
Of the bones of the pectoral girdle the clavicle requires further study before it can be certain whether it is to be regarded as a purely cartilage bone or as a combination of cartilage and membrane ossification (Gegenbaur). It is the first bone of the skeleton to ossify, two centers appearing for each bone at about the sixth week of development. The tissue in which the ossifications form has certain peculiar characters, and it is difficult to say whether it is to be regarded as cartilage which, on account of the early differentiation of the center, has not yet become thoroughly differentiated histologically, or as some other form of connective tissue. However that may be, true cartilage develops on either side of the ossifying region, and into this the ossification gradually extends, so that at least a portion of the bone is preformed in cartilage.
The scapula is at first a single plate of cartilage in which two centers of ossification appear. One of these gives rise to the body and the spine, while the other produces the coracoid process (Fig. 113, co), the rudimentary representative of the coracoid bone which extends between the scapula and sternum in the lower vertebrates. The coracoid does not unite with the body until about the fifteenth year, and secondary centers which give rise to the vertebral edge (b) and inferior angle of the bone (a) and to the acromion process (c) unite with the rest of the bone at about the twentieth year.
1 84
The humerus and the bones of the forearm are typical long bones, each of which develops from a primary center, which gives rise to the shaft, and has, in addition, two or more epiphysial centers. In the humerus an epiphysial center appears for the head, another for the greater tuberosity, and usually a third for the lesser tuberosity, while at the distal end there is a center for each condyle, one for the trochlea and one for the capitulum, the fusion of these various epiphyses with the shaft taking place between the seventeenth and
Fig. 113.  -  The Ossification Centers of the Scapula. a, b, and c, Secondary centers for the angle, vertebral border, and acromion; co, center for the coracoid process.  -  (Testut.)
Fig. 114.  -  Reconstruction of an Embryonic Carpus.
c, Centrale; cu, triquetral; lu, lunate; m, capitate; p, pisiform; sc, navicular; t, greater multangular; tr, lesser multangular; u, hamate.
twentieth years. The radius and ulna each possesses a single epiphysial center for each extremity in addition to the primary center for the shaft, the proximal epiphysial center for the ulna giving rise to the tip of the olecranon process.
The embryological development of the carpus is somewhat complicated. A cartilage is found representing each of the bones normally occurring in the adult (Fig. 114), and these are arranged in two distinct rows: a proximal one consisting of three elements,
named from their relation to the bones of the forearm, radiate, intermedium, and ulnar e; and a distal on^composed of four elements, termed carpalia. In addition, a cartilage, termed the pisiform, is found on the ulnar side of the proximal row ^nd is generally j^g&rded as a sesamoid cartilage developed in the /tendon of the flei ulnaris, and furthermore a number of inconstant carti been observed whose significance in the majority of cast less obscure. These accessory cartilage^either disappc stages of development or fuse with neighboring cartilages^ cases, ossify and form distinct elements of the carpus, however, occurs so frequently as almdK to deserve^ classification as a constant element; it \p known asvthje ceniraie (Fig. 114, c) and occupies a position between the/car\ua!§;es of the proximal and distal rows and apparently correspond ~r&. a cartilage typVally present in lower forms and o^fying*to~f»rai a distinct bone. Iri tha human carpus its fate varies, wfe it may\eitnfer disappear or unitp with other cartilages, that with wpich it most usually fuses b'eing probably the radiale. There is evraence also to sfrftw that another ofJthe accessory cartilages unites/with the ulnar element of the distatsAw, representing the carpale v typically present in lower forms.
Each of the eleinents corresponding to an adu^t) bone ossifies
from a single centerwith the exception of carpale iv-Xwhich has two centers, a furtherindication of its composite character. The relation of the cartrteg&s to the adult bones may be seen from the table given on page loX^J \v_^
With regard toYhe metacarpals and phalanges; it need merely be stated that each develops from a single primary center for the shaft and one secondary epiphysial center. The" primary center appears at about the middle of the shaft excepJ in the terminal phalanges, in which it appears at the distal enfr of the cartilage. The epiphyses for the metacarpals are at the distends of the bones, except in the case of the metacarpal of the ihumb, which resembles the phalanges in having its epiphysis at the proximal end.
Each innominate bone appears as a somewhat oval plate of cartilage whose long axis is directed almost at right angles to the
vertebral column and which is in close relation with the fourth and fifth sacral vertebrae. As development proceeds a rotation of the cartilage, accompanied by a slight shifting of position, occurs, so that eventually the plate has its long axis almost parallel with the vertebral column and is in relation with the first three sacrals. Ossification appears at three points in each cartilage, one in the
upper part to form the ilium (Fig. 115, il) and two in the lower part, the anterior of these giving rise to the pubis (p), while the posterior produces the ischium (is). At birth these three bones are still separated from one another by a Y-shaped piece of cartilage whose three limbs meet at the bottom of the acetabulum, but later a secondary center appears in this cartilage and unites the three bones together. The central part of the lower half of each original cartilage plate does not undergo complete chondrification, but remains membranous, constituting the obturator membrane which closes the obturator foramen. In addition to the Y-shaped secondary center, other epiphysial centers appear in the prominent portions of the cartilage, such as the pubic crest (Fig. 115, c), the ischial tuberosity (d), the anterior inferior spine (b) and the crest of the ilium (a), and unite with the rest of the bone at about the twentieth year.
The femur, tibia, and fibula each develop from a single primary center for the shaft and an upper and a lower epiphysial center, the femur possessing, in addition, epiphysial centers for the greater and lesser trochanters (Fig. 94). The patella does not belong to the same category as the other bones, but resembles the pisiform
Fig. 115.  -  The Ossification Centers of the os innominatum. a, b, c, and d, Secondary centers for the crest, anterior inferior spine, symphysis, and ischial tuberosity; il, ilium; is, ischium; p, pubis.  -  (Testut.)
l8 7
bone of the carpus in being a sesamoid bone, developed in the tendon of the quadriceps extensor cruris. Its cartilage does not appear until the fourth month of intrauterine life, when most of the primary centers for other bones have already appeared, and its ossification does not begin until the third year after birth.
The tarsus, like the carpus, consists of a proximal row of three cartilages, termed the tibiale, the intermedium, and the fibulare, and of a distal row of four tarsalia. Between these two rows a single cartilage, the centrale, is interposed. Each of these cartilages ossifies from a single center, that of the intermedium early fusing with the tibiale, though it occasionally remains distinct as the os trigonum, and from a comparison with lower forms it seems probable that the fibular cartilage of the distal row really represents two separate elements, there being, properly speaking, five tarsalia instead ot four. The fibulare, in addition to its primary center, possesses also an epiphysial center, which develops at the point of insertion of the tendo Achillis.
A comparison of the carpal and tarsal cartilages and their relations to the adult bones may be seen from the following table:
f Tibiale
\ Intermedium
Sesamoid cartilage
-  - 
Fuses with navicular
Carpale I
Gr. multangular
1 st Cuneiform
Tarsale I
Carpale II
Less, multangular
2d Cuneiform
Tarsale II
Carpale III
3d Cuneiform
Tarsale III
Carpale IV 1 Carpale V J
( Tarsale TV I Tarsale V
The development of the metatarsals and phalanges is exactly similar to that of the corresponding bones of the hand (see p. 185).
The Development of the Joints.  -  The mesenchyme which primarily represents each, vertebra, or the skull, or the skeleton of a limb, is at first a continuous mass, and when it becomes converted into cartilage this also may be continuous, as in the skull, or may appear as a number of distinct parts united by unmodified portions of the mesenchyme. In the former case the various ossifications as they extend will come into contact with their neighbors and will either fuse with them or will articulate with them directly, forming a suture.
When, however, a portion of unmodified mesenchyme intervenes between two cartilages, the mode of articulation of the bones formed from these cartilages will vary. The intermediate mesenchyme may in time undergo chondrification and unite the bones in an almost immovable articulation known as a synchondrosis (e. g., the articulation of the first rib with the sternum) ; or a cavity may appear in the center of the intervening cartilage so that a slight amount of movement of the two bones is possible, forming an amphiar thro sis (e. g., the symphysis pubis); or, finally, the intermediate mesenchyme may not chondrify, but its peripheral portions may become converted into a dense sheath of connective tissue (Fig. 116, c) which surrounds the adjacent ends of the two bones like a sleeve, forming the articular capsule, while the central portions degenerate to form a cavity. The bones which enter into such an articulation are more or less freely movable upon one another and the joint is termed a diarthrosis (e. g., the knee- or shoulder-joint).
In a diarthrosis the connective-tissue cells near the inner surface of the capsule arrange themselves in a layer to form a synovial membrane for the joint, and portions of the capsule may thicken to form special bands, the reinforcing ligaments, while other strong fibrous bands, which may pass from one bone to the other, forming accessory ligaments, are shown by comparative studies to be in many cases degenerated portions of what were originally muscles.
In certain diarthroses, such as the temporo-mandibular and
sternoclavicular, the whole of the central portions of the intermediate mesenchyme does not degenerate, but it is converted into a fibro-cartilage, between each surface of which and the adjacent bone there is a cavity. These interarticular cartilages seem, in the sterno-clavicular joints, to represent the sternal ends of a bone existing in lower vertebrates and known as the precoracoid, but it seems doubtful if those of the temporo-mandibular and knee
Fig. 116. -  Longitudinal Section through the Joint oe the Great Toe in an
Embryo of 4.5 cm. c, Articular capsule; i, intermediate mesenchyme which has almost disappeared in the center; p 1 and p 2 , cartilages of the first and second phalanges.  -  (Nicholas.)
joints have a similar significance, the most recent observations on their development tending to derive them from the intermediate mesenchyme.
From their mode of development it is evident that the cavities of diarthrodial joints are completely closed and their walls, except where they are formed by cartilage, are lined by a continuous layer of synovial cells. Ligaments or tendons, which, at first sight, appear to traverse the cavities of certain joints, are in reality excluded from them, being lined by a sheath of synovial cells continuous with the layer fining the general cavity. Thus, the tendon of the long head of the biceps, which seems to traverse the shoulder-joint is, in the fetus, entirely outside the articular capsule, upon which it rests. Later it sinks in toward the joint cavity, pushing the articular capsule before it, so that it lies at first in a groove in the capsule, which later on becomes converted into a canal and, finally, separates from the rest of the capsule except at its two extremities,
forming a cylindrical canal, open at either end, traversing the joint cavity and containing the tendon of the biceps.
The ligamentum teres of the hip-joint is similarly excluded from the joint cavity by a sheath of synovium, which extends outward around it from the bottom of the acetabular fossa to the depression in the head of the femur, and in the knee-joint the crucial ligaments are also excluded from the cavity by a reflection of the synovium. This joint, indeed, is in the fetus incompletely divided into two parts, one corresponding to each femoral condyle, by a partition which extends backward from the patellar ligament to the crucial ligaments, remains of this partition persisting in the adult as the so-called ligamentum mucosum.
C. R. Bardeen: " The Development of the Thoracic Vertebrae in Man," Amer. Journ.
Anat., iv, 1905. C. R. Bardeen: "Studies of the Development of the Human Skeleton," Amer
Journ. Anat. iv, 1905. C. R. Bardeen: "Early Development of the Cervical Vertebra and the Base of the
Occipital Bone in Man," Amer. Journ. Anat., vm, 1908. C. R. Bardeen: "Vertebral Regional Determination in Young Human Embryos,"
Anat. Record, 11, 1908. E. T. Bell: "On the Histogenesis of the Adipose Tissue of the Ox," Amer. Journ.
Anat., ix, 1909. A. Bernays: "Die Entwicklungsgeschichte des Kniegelenks des Menschen mit
Bemerkungen liber die Gelenke im Allgemeinen," Morpholog. Jahrbuch, TV, 1878. E. Dtjrsy: "Zur Entwicklungsgeschichte des Kopfes des Menschen und der hoheren
Wirbelthiere," Tubingen, 1869. E. Fawcett: "On the Development, Ossification and Growth of the Palate Bone,"
Journ. Anat. and Phys., XL, 1906. E. Fawcett: "Notes on the Development of the Human Sphenoid," Journ. Anat.
and Phys., xliv, 1910. E. Fawcett: "The Development of the Human Maxilla, Vomer and Paraseptal Cartilages," Journ. Anat. and Phys., xlv, 1911. A. Froriep: "Zur Entwicklungsgeschichte der Wirbelsaule, insbesondere des Atlas
und Epistropheus und der Occipitalregion," Archiv fur Anat. und Physiol., Anat.
Abth., 1886. E. Gaupp: "Alte Probleme und neuere Arbeiten iiber den Wirbeltierschadel," Ergeb.
der Anat. und Entwicklungsgesch., x, 1901. C. Gegenbaur: "Ein Fall von erblichem Mangel der Pars acromialis Claviculae, mit
Bemerkungen iiber die Entwicklung der Clavicula," Jenaische Zeitschr.filr medic.
Wissensch., I, 1864. J. Golowinski: "Zur Kenntnis der His.togenese der Bindegewebsfibrillen," Anat.
Hefte, xxxiii, 1907.
E. Grafenberg: "Die Entwirklung der Knochen, Muskeln unci Nerven der Hand und
der fur die Bewegungen der Hand bestimmten Muskeln des Unterarms," Anat.
Hefte, xxx, 1906. Henkeand Reyher: "Studien liber die Entwickelung der Extremitaten des Menschen,
insbesondere der Gelenkflachen," Sitzungsberichte der kais. Akad. Wien, LXX, 1875. M. Jakoby: "Beitrag zur Kenntnis des menschlichen Primordialcraniums," Archiv
fiir mikrosk. Anat., xliv, 1894. K. Kjellberg: "Beitrage zur Entwicklungsgeschichte des Kiefergelenks," Morph.
Jahrbuch, xxxii, 1904. H. Leboucq: "Recherches sur la morphologie du carpe chez les mammiferes,"
Archives de Biolog., V, 1884. G. Levi: "Beitrag zum Studium der Entwickelung des knorpeligen Primordialcraniums des Menschen," Archiv fiir mikrosk. Anat., lv, 1900. A. Linck: "Beitrage zur Kennlnis der menschlichen Chorda dorsalis in Hals- und
Kopfskelett, etc.," Anat. Hefte, xlii, 1911. A. Low: "Further Observations on the Ossification of the Human Lower Jaw,"
Journ. Anat. and Phys., xliv, 1910. M. Lucien: " Developpement de l'articulation du genou et formation du ligament
adipeux," Bibliogr. Anat., xiii, 1904.
F. P. Mall: "The Development of the Connective Tissues from the Connective-tissue
Syncytium," Amer. Jour. Anat., 1, 1902. F. P. Mall: "On Ossification Centers in Human Embryos Less Than One Hundred Days Old," Amer. Journ. Anat., V 1906.
F. Merkel: "Betrachtungen fiber die Entwicklung des Bindegewebes," Anat. Hefte,
xxxviii, 1909. W. van Noorden: "Beitrag zur Anatomie der knorpeligen Schadelbasis menschlicher
Embryonen," Archiv fiir Anat. und Physiol., Anat. Abth., 1887. A. M. Paterson: "The Human Sternum," Liverpool, 1904. K. Peter: " Anlage und Homologie der Muscheln des Menschen und der Saugetiere,"
Arch, fur mikrosk. Anat., lx, 1902. J. W. Pryor: "The Chronology and Order of Ossification of the Bones of the Human
Carpus," Bulletin State Univ., Lexington, Ky., 1908. Rambaut et Renault: "Origine et developpement des Os," Paris, 1864. E. Rosenberg: "Ueber die Entwickelung der Wirbelsaule und das Centrale carpi des
Menschen," Morpholog. Jahrbuch, 1, 1876. H. and H. Rouviere: "Sur le developpement de l'antre mastoidien et les cellules
mastoidiennes," Bibliogr. Anat., xx, 1910.
G. Ruge: " Untersuchungen liber die Entwickelungsvorgange am Brustbein des Menschen," Morpholog. Jahrbuch, VI, 1880.
J. P. Schaffer: "The Lateral Wall of the Cavum Nasi in Man, with Especial Reference to the Various Developmental Stages," Journ. Morph., xxi, 1910.
J. P. Schaffer: "The Sinus Maxillaris and its Relations in the Embryo, Child and Adult Man," Amer Journ. Anat., x, 1910.
G. Thilenius: "Untersuchungen iiber die morphologische Bedeutung accessorischer Elemente am menschlichen Carpus (und Tarsus)," Morpholog. Arbeiten, V, 1896.
K. Toldt Jr.: "Entwicklung und Struktur des menschlichen Jochbeines," Sitzungsber.
k. Acad. Wissensch. Wien, M ath.-naturwiss Kl., Cxi, 1902. A. Vinogradoff: "Developpement de l'articulation temporo-maxillaire chez l'homme
dans la periode intrauterine," Internal. Monatsschr. Anat. Phys., xxvil, 1910. R. H. Whitehead and J. A. Waddell: "The Early Development of the Mammalian
Sternum," Amer. Journ. Anat., xii, 191 1. L. W. Williams: "The Later Development of the Notochord," Amer. Journ. Anat.,
vin, 1908. E. Zuckerkandl: "Ueber den Jacobsonschen Knorpel und die Ossifikation des
Pflugscharbeines," Sitzb. Akad. Wiss. Wien., cxvn, 1908.
Two forms of muscular tissue exist in the human body, the striated tissue, which forms the skeletal muscles and is under the control of the central nervous system, and the non-striated, which is controlled by the sympathetic nervous system and is found in the skin, in the walls of the digestive tract, the blood-vessels and lymphatics, and in connection with the genito-urinary apparatus. In the walls of the heart a muscle tissue occurs which is frequently regarded as a third form, characterized by being under control of the sympathetic system and yet being striated; it is, however, in its origin much more nearly allied to the non-striated than to the striated form of tissue, and will be considered a variety of the former.
The Histogenesis of Non-striated Muscular Tissue.  -  With the exception of the sphincter and dilator of the pupil and the muscles of the sudoriparous glands, which are formed from the ectoderm, all the non-striated muscle tissue of the body is formed by the conversion of mesenchyme cells into muscle-fibers. The details of this process have been worked out by McGill for the musculature of the digestive and respiratory tracts of the pig and are as follows: The mesenchyme surrounding the mucosa in these tracts is at first a loose syncytium (Fig. 117, m) and in the regions where the muscle tissue is to form a condensation of the mesenchyme occurs followed by an elongation of the mesenchyme cells and their nuclei, so that the muscle layers become clearly distinguishable from the neighboring undifferentiated tissue (Fig. 117, mm). Fibrils of two kinds then begin to appear in the cytoplasm of the muscle cells. Coarse fibrils (f.c) make their appearance as rows of granules, which enlarge and increase in number until they finally fuse to form homogeneous 13 i93
Fig. 117.  -  Longitudinal Section of the Lower Part of the Oesophagus of a Pig Embryo of 15 mm, Showing the Histogenesis of the Non-striated Musculature.
b, Basement membrane; e, epithelium; /.c, coarse fibril;//., fine fibril; ga, ganglion of Auerbach's plexus; gm, ganglion of Meissner's plexus; m, mesenchyne; mm, muscularis mucosae; pb, protoplasmic bridge; vf, varicose fibril.  -  (McCill.)
J 95
fibrils that are at first varicose, but later become of uniform caliber. Fine fibrils (/./) which are homogeneous from the first, make their appearance after the coarse ones and in some cases seem to be formed by the splitting of the latter. They are scattered uniformly throughout the cytoplasm of the muscle cells and increase in number as development proceeds, while the coarse fibrils diminish and may be entirely wanting in the adult tissue.
Some of the mesenchyme cells in each muscle sheet fail to undergo the differentiation just described and multiply to form the interstitial connective tissue, which usually divides the muscle cells into more or less distinct bundles. Traces of the original syncytial nature of the tissue are to be seen in the intercellular bridges that occur between the non-striated muscle cells of many adult forms.
The cells from which the heart musculature develops are at first of the usual well defined embryonic type, but, as development proceeds, they become irregularly stellate in form, the processes of neighboring cells fuse and, eventually, there is formed a continuous mass of protoplasm or syncytium in which all traces of cell boundaries are lacking (Fig. 118). While the individual cells, or myoblasts as they are termed, are still recognizable, granules appear in their cytoplasm, and these arrange themselves in rows and unite to form slender fibrils, which at first do not extend beyond the limits of the myoblasts in which they have appeared, but later, as the fusion of the cells proceeds, are continued from one cell territory into the other
Fig. 118.  -  Section through the Heartwall of a Duck Embryo of Three Days.  -  (M. Heidenhain.)
through considerable stretches of the syncytium, without regard to the original cell areas.
The fibrils multiply, apparently by longitudinal division, and arrange themselves in circles around areas of the syncytium (compare Fig. 119). As the multiplication of the fibrils continues those newly formed arrange themselves around the interior of each of the original circles and gradually occupy the entire cytoplasm, or sarcoplasm as it may now be termed, except immediately around the nuclei where, even in the adult, a certain amount of undifferentiated sarcoplasm persists. The fibrils when first formed are apparently homo
Fig. 119.  -  Cross-section of a Muscle prom the Thigh of a Pig Embryo 75 mm.
Long. A, Central nucleus; B, new peripheral nucleus.  -  (Macallum.)
geneous, but later they become differentiated into two distinct substances which alternate with one another throughout the length of the fibril and produce the characteristic transverse striation of the tissue. Finally stronger interrupted transverse bands of so-called cement substance appear, dividing the tissue into areas which have usually been regarded as representing the original myoblasts, but are really devoid of significance as cells, the tissue remaining, strictly speaking, a syncytium.
The Histogenesis of Striated Muscle Tissue. -  The histogenesis of striated or voluntary muscle tissue resembles very closely that which has just been described for the heart muscle. There is a similar formation of a syncytium by the fusion of the cells of the myotomes, an appearance of granules which unite to form fibrils, an increase of the fibrils by longitudinal division and a primary arrangement of the fibrils around the periphery of areas of sarcoplasm (Fig. 119), each of which represents a muscle fiber. In addition there is an active proliferation of the nuclei of the original myoblasts, the new nuclei arranging themselves more or less regularly in rows and later migrating from their original central position to the periphery of the fibers, and, in the limb muscles, the development is further complicated by a process of degeneration which affects groups of muscle fibers, so that bundles of normal fibers are separated by strands of degenerated tissue in which the fibrils have disappeared, the nuclei have become pale and the sarcoplasm vacuolated and homogeneous. Later the degenerated tissue seems to disappear entirely and mesenchymatous connective tissue grows in between the persisting fibers, grouping them into bundles and the bundles into the individual muscles.
So long as the formation of new fibrils continues, the increase in the thickness of a muscle is probably due to a certain extent to an increase in the actual number of fibers, which results from the division of those already existing. Subsequently, however, this mode of growth ceases, the further increase of the muscle depending upon an increase in size of its constituent elements (Macallum).
The Development of the Skeletal Muscles.  -  It has already been pointed out that all the skeletal muscles of the body, with the exception of those connected with the branchial arches, are derived from the myotomes of the mesodermic somites, even the limb muscles possibly having such an origin, although the cells of the tissue from which the muscles of the limb buds form lack an epithelial arrangement and are indistinguishable from the somatic mesenchyme which forms the axial cores of the limbs.
The various fibers of each myotome are at first loosely arranged,
but later they become more compact and are arranged parallel with one another, their long axes being directed antero-posteriorly. This stage is also transitory, however, the fibers of each myotome undergoing various modifications to produce the conditions existing in the adult, in which the original segmental arrangement of the fibers can be perceived in comparatively few muscles. The exact nature of these modifications is almost unknown from direct observation, but since the relation between a nerve and the myotome belonging to the same segment is established at a very early period of development and persists throughout life, no matter what changes of fusion, splitting, or migration the myotome may undergo, it is possible to trace out more or less completely the history of the various myotomes by determining their segmental innervation. It is known, for example, that the latissimus dorsi arises from the seventh and eighth* cervical myotomes, but later undergoes a migration, becoming attached to the lower thoracic and lumbar vertebrae and to the crest of the ilium, far away from its place of origin (Mall), and yet it retains its nerve-supply from the seventh and eighth cervical nerves with which it was originally associated, its nerve-supply consequently indicating the extent of its migration.
By following the indications thus afforded, it may be seen that the changes which occur in the myotomes may be referred to one or more of the following processes:
1. A longitudinal splitting into two or more portions, a process well illustrated by the trapezius and sternomastoid, which have differentiated by the longitudinal splitting of a single sheet and contain therefore portions of the same myotomes. The sternohyoid and omohyoid have also differentiated by the same process, and, indeed, it is of frequent occurrence.
2. A tangential splitting into two or more layers. Examples of this are also abundant and are afforded by the muscles of the fourth, fifth, and sixth layers of the back, as recognized in English text-books
* This enumeration is based on convenience in associating the myotomes with the nerves which supply them. The myotomes mentioned are those which correspond to the sixth and seventh cervical vertebrae.
of anatomy, by the two oblique and the transverse layers of the abdominal walls, and by the intercostal muscles and the transversus of the thorax.
3. A fusion of portions of successive myotomes to form a single muscle, again a process of frequent occurrence, and well illustrated by the rectus abdominis (which is formed by the fusion of the ventral portions of the last six or seven thoracic myotomes) or by the superficial portions of the sacro-spinalis.
4. A migration of parts of one or more myotomes over others. An example of this process is to be found in the latissimus dorsi, whose history has already been referred to, and it is also beautifully shown by the serratus anterior and the trapezius, both of which have extended far beyond the limits of the segments from which they are derived.
5. A degeneration of portions or the whole of a myotome. This process has played a very considerable part in the evolution of the muscular system in the vertebrates. When a muscle normally degenerates, it becomes converted into connective tissue, and many of the strong aponeurotic sheets which occur in the body owe their origin to this process. Thus, for example, the aponeurosis connecting the occipital and frontal portions of the occipito-frontalis is formed in this process and is muscular in such forms as the lower monkeys, and a good example is also to be found in the aponeurosis which occupies the interval between the superior and inferior serrati postici, these two muscles being continuous in lower forms. The strong lumbar aponeurosis and the aponeuroses of the oblique and transverse muscles of the abdomen are also good examples.
Indeed, in comparing one of the mammals with a member of one of the lower classes of vertebrates, the greater amount of connective tissue compared with the amount of muscular tissue in the former is very striking, the inference being that these connectivetissue structures (fasciae, aponeuroses, ligaments) represent portions of the muscular tissue of the lower form (Bardeleben). Many of the accessory ligaments occurring in connection with diarthrodial joints apparently owe their origin to a degeneration of muscle tissue, the
fibular lateral ligament of the knee-joint, for instance, being probably a degenerated portion of the peroneus longus, while the sacrotuberous ligament appears to stand in a similar relation to the long head of the biceps femoris (Sutton).
6. Finally, there may be associated with any of the first four processes a change in the direction of the muscle-fibers. The original antero-posterior direction of the fibers is retained in comparatively few of the adult muscles and excellent examples of the process here referred to are to be found in the intercostal muscles and the muscles of the abdominal walls. In the musculature associated with the branchial arches the alteration in the direction of the fibers occurs even in the fishes, in which the original direction of the muscle-fibers is very perfectly retained in other myotomes, the branchial muscles, however, being arranged parallel with the branchial cartilages or even passing dorso-ventrally between the upper and lower portions of an arch, and so forming what may be regarded as a constrictor of the arch. This alteration of direction dates back so far that the constrictor arrangement may well be taken as the primary condition in studying the changes which the branchial musculature has undergone in the mammalia.
It would occupy too much space 'in a work of this kind to consider in detail the history of each one of the skeletal muscles of the human body, but a statement of the general plan of their development will not be out of place. For convenience the entire system may be divided into three portions  -  the cranial, trunk and limb musculature; and of these, the trunk musculature may first be considered.
The Trunk Musculature.  -  It has already been seen (p. 82) that the myotomes at first occupy a dorsal position, becoming prolonged ventrally as development proceeds so as to overlap the somatic mesoderm, until those of opposite sides come into contact in the mid-ventral line. Before this is accomplished, however, a longitudinal splitting of each myotome occurs, whereby there is separated off a dorsal portion which gives rise to a segment of the dorsal musculature of the trunk and is supplied by the ramus dorsalis
of its corresponding spinal nerve. In the lower vertebrates this separation of each of the trunk myotomes into a dorsal and ventral portion is much more distinct in the adult than it is in man, the two portions being separated by a horizontal plate of connective tissue extending the entire length of the trunk and being attached by its inner edge to the transverse processes of the vertebrae, while peripherally it becomes continuous with the connective tissue of the
Fig. 120.  -  Embryo of 13 mm. showing the Formation of the Rectus Muscle. - 
dermis along a line known as the lateral line. In man the dorsal portion is also much smaller in proportion to the ventral portion than in the lower vertebrates. From this dorsal portion of the myotomes are derived the muscles belonging to the three deepest layers of the dorsal musculature, the more superficial layers being
composed of muscles belonging to the limb system. Further longitudinal and tangential divisions and a fusion of successive myotomes bring about the conditions which obtain in the adult dorsal musculature.
While the myotomes are still some distance from the mid-ventral line another longitudinal division affects their ventral edges (Fig. 120), portions being thus separated which later fuse more or less perfectly to form longitudinal bands of muscle, those of opposite sides being brought into apposition along the mid-ventral line by the continued growth ventrally of the myotomes. In this way are formed the rectus and pyramidalis muscles of the abdomen and the depressors of the hyoid bone, the genio-hyoid and genio-glossus* in the neck region. In the thoracic region this rectus set of muscles, as it may be termed, is not represented except as an anomaly, its absence being probably correlated with the development of the sternum in this region.
The lateral portions of the myotomes which intervene between the dorsal and rectus muscles divide tangentially, producing from their dorsal portions in the cervical and lumbar regions muscles, such as the longus capitis and colli and the psoas, which lie beneath the vertebral column and hence have been termed hyposkeletal muscles (Huxley). More ventrally three sheets of muscles, lying one above the other, are formed, the fibers of each sheet being arranged in a definite direction differing from that found in the other sheets. In the abdomen there are thus formed the two oblique and the transverse muscles, in the thorax the intercostals and the transversa thoracis, while in the neck these portions of some of the myotomes disappear, those of the remainder giving rise to the scaleni muscles, portions of the trapezius and sternomastoid (Bolk), and possibly the hyoglossus and styloglossus. In the abdominal region, and to a considerable extent in the neck also, the various portions of myotomes fuse together, but in the thorax they retain in the intercostals their original distinctness, being separated by the ribs.
* This muscle is supplied by the hypoglossal nerve, but for the present purpose it is convenient to regard this as a spinal nerve, as indeed it primarily is.
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The table on page 203 will show the relation of the various trunk muscles to the portions of the myotomes.
The intimate association between the pelvic girdle and the axial skeleton brings about extensive modifications of the posterior trunk myotomes. So far as their dorsal portions are concerned probably all these myotomes as far back as the fifth sacral are represented in the sacro-spinalis, but the ventral portions from the first lumbar myotome onward are greatly modified. The last myotome taking part in the formation of the rectus abdominis is the twelfth thoracic and the last to be represented in the lateral musculature of the
Fig. 121.  -  Perineal Region of Embryos of (A) Two Months and (25) Four to
Five Months, showing the Development of the Perineal Muscles.
dc, Nervus dorsalis clitoridis; p, pudendal nerve; sa, sphincter ani; sc sphincter cloacae;
sv, sphincter vaginse.  -  (Popowsky.)
abdomen is the first lumbar, the ventral portions of the remaining lumbar and of the first and second sacral myotomes either having disappeared or being devoted to the formation of the musculature of the lower limb.
The ventral portions of the third and fourth sacral myotomes are represented, however, by the levator ani and coccygeus, and are the last myotomes which persist as muscles in the human body, although traces of still more posterior myotomes are to be found in muscles such as the curvator coccygis sometimes developed in connection with the coccygeal vertebrae.
The perineal muscles and the external sphincter ani are also
developments of the third and fourth (and second) sacral myotomes. At a time when the cloaca (see p. 280) is still present, a sheet of muscles lying close beneath the integument forms a sphincter around its opening (Fig. 121). On the development of the partition which divides the cloaca into rectal and urinogenital portions, the sphincter is also diyided, its more posterior portion persisting as the external sphincter ani, while the anterior part gradually differentiates into the various perineal muscles (Popowsky).
The Cranial Musculature.  -  As was pointed out in an earlier chapter, the existence of distinct mesodermic somites has not yet been completely demonstrated in the head of the human embryo, but in lower forms, such as the elasmobranch fishes, they are clearly distinguishable, and it may be supposed that their indistinctness in man is a secondary condition. Exactly how many of these somites are represented in the mammalian head it is impossible to say, but it seems probable, from comparison with lower forms, that there is a considerable number. The majority of them, however, early undergo degeneration, and in the adult condition only three are recognizable, two of which are prseoral in position and one postoral. The myotomes of the anterior praeoral segment give rise to the muscles of the eye supplied by the third cranial nerve, those of the posterior one furnish the superior oblique muscles innervated by the fourth nerve, while from the postoral myotomes the lateral recti, supplied by the sixth nerve, are developed. The muscles supplied by the hypoglossal nerve are also derived from myotomes, but they have already been considered in connection with the trunk musculature.
The remaining muscles of the head differ from all other voluntary muscles of the body in the fact that they are derived from the branchiomeres formed by the segmentation of the cephalic ventral mesoderm. These muscles, therefore, are not to be regarded as equivalent to the myotomic muscles if their embryological origin is to be taken as a criterion of equivalency, and in their case it would seem, from the fact that they are innervated by nerves fundamentally distinct from those which supply the myotomic muscles, that this
criterion is a good one. They must be regarded, therefore, as belonging to a special category, and may be termed branchiomeric muscles to distinguish them from the myotomic set.
If their embryological origin be taken as a basis for homology, it is clear that they should be regarded as equivalent to the muscles derived from the ventral mesoderm of the trunk, and these, as has been seen, are the non-striated muscles associated with the viscera, among which may be included the striated heart muscle. At first sight this homology seems decidedly strained, chiefly because long-continued custom has regarded the histological and physiological peculiarities of striated and non-striated muscle tissue as fundamental. It may be pointed out, however, that the branchiomeric muscles are, strictly speaking, visceral muscles, and indeed give rise to muscle sheets (the constrictors of the pharynx) which surround the upper or pharyngeal portion of the digestive tract. It is possible, then, that the homology is not so strained as might appear, but further discussion of it may profitably be deferred until the cranial nerves are under consideration.
The skeleton of the first branchial arch becomes converted partly into the jaw apparatus and partly into auditory ossicles, and the muscles derived from the corresponding branchiomere become the muscles of mastication (the temporal, masseter, and pterygoids), the mylohyoid, anterior belly of the digastric, the tensor veli palatini and the tensor tympani. The nerve which corresponds to the first branchial arch is the trigeminus or fifth, and consequently these various muscles are supplied by it.
The second arch has corresponding to it the seventh nerve, and its musculature is partly represented by the stylohyoid and posterior belly of the digastric and by the stapedius muscle of the middle ear. From the more superficial portions of the branchiomere, however, a sheet of tissue arises which gradually extends upward and downward to form a thin covering for the entire head and neck, its lower portion giving rise to the platysma and the nuchal fascia which extends backward from the dorsal border of this muscle, while its upper parts become the occipito-frontalis and the superficial muscles of the face (the muscles of expression), together with the fascia? which unite the various muscles of this group. The extension of the platysma sheet of muscles over the face is well shown by the
Fig. 122.  -  Head of Embryos (.4) of Two Months and (B) of Three Months showing the Extension of the Seventh Nerve upon the Face.  -  (Popowsky.)
development of the branches of the facial nerve which supply it (Fig. 122).
The degeneration of the upper part of the third arch produces a shifting forward of one of the muscles derived from its branchiomere, the stylopharyngeus arising from the base of the styloid process. The innervation of this muscle by the ninth nerve indicates, however, its true significance, and since fibers of this nerve of the third arch also pass to the constrictor muscles of the pharynx, a portion of these must also be regarded as having arisen from the third branchiomere.
The cartilages of the fourth and fifth arches enter into the formation of the larynx and the muscles of the corresponding branchiomeres constitute the muscles of the larynx, together with the remaining portions of the constrictors of the pharynx and the muscles of the soft palate, with the exception of the tensor. Both these arches have branches of the tenth nerve associated with them and hence this nerve supplies the muscles named. In addition, two of the extrinsic muscles of the tongue, the glosso-palatinus and chondroglossus, belong to the fourth or fifth branchiomere, although the remaining muscles of this physiological set are myotomic in origin.
Finally, portions of two other muscles should probably be included in the list of branchiomeric muscles, these muscles being the trapezius and sternomastoid. It has already been seen that they are partly derived from the cervical myotomes, but they are also innervated in part by the spinal accessory, and since the motor fibers of this nerve are serially homologous with those of the vagus it would seem that the muscles which they supply are probably branchiomeric in origin. Observations on the development of these muscles, determining their relations to the branchiomeres, are necessary, however, before their morphological significance can be regarded as definitely settled.
The table on page 209 shows the relations of the various cranial muscles to the myotomes and branchiomeres, as well as to the motor cranial nerves.
Trapezius. Sternomastoid.
Constrictors of pharynx (in part). Pharyngopalatinus. Levator veli palatini. Musculus
uvulae. Muscles of the larynx. Glosso-pal
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The Limb Muscles.  -  It has been customary to regard the limb muscles as derivatives of certain of the myotomes, these structures in their growth vent rally in the trunk walls being supposed to pass out upon the postaxial surface of the limb buds and loop back again to the trunk along the praeaxial surface, each myotome thus giving rise to a portion of both the dorsal and the ventral musculature of the limb. This view has not, however, been verified by direct observation of an actual looping of the myotomes over the axis of the limb buds; indeed, on the contrary, the limb muscles have been found to develop from the cores of mesenchyme which form the axes of the limb buds and from which the limb skeleton is also developed. This may be explained by supposing that the limb muscles are primarily derivatives of the myotomes and that an extensive concentration of their developmental history has taken place, so that the axial mesenchyme actually represents myotomic material even though no direct connection between it and the myotomes can be discovered. Condensations of the developmental history certainly occur and the fact that the muscles of the human limbs, as they differentiate from the axial cores, present essentially the same arrangement as in the adult seems to indicate that there is actually an extensive condensation of the phylogenetic history of the individual muscles, since comparative anatomy shows the arrangement of the muscles of the higher mammalian limbs to be the result of a long series of progressive modifications from a primitive condition. However, even though this be the case, there is yet the possibility that the limb musculature, like the limb skeleton, may take its origin from the ventral mesoderm and consequently belong to a different embryological category from the axial myotomic muscles.
The strongest evidence in favor of the myotomic origin of the limb muscles is that furnished by their nerve supply, this presenting a distinctly segmental arrangement. This does not necessarily imply, however, a corresponding primarily metameric arrangement of the muscles, any more than the pronouncedly segmental arrangement of the cutaneous nerves implies a primary metamerism of the
dermis (see p. 143). It may mean only that the nerves, being segmental, retain their segmental relations to one another even in their distribution to non-metameric structures, and that, consequently, the limb musculature is supplied in succession from one border of the limb bud to the other from succeeding nerve roots.
But whether further observation may prove or disprove the myotomic origin of the limb musculature, the fact remains that it possesses a segmentally arranged innervation, and it is possible,
Fig. 123.  -  Diagram of a Segment of the Body and Limb. bl, Axial blastema; dm, dorsal musculature of trunk; rl, nerve to limb; s, septum between dorsal and ventral trunk musculature; str.d, dorsal layer of limb musculature; tr.d and tr.v, dorsal and ventral divisions of a spinal nerve; vm, ventral musculature of the trunk.  -  (Kollmann.)
therefore, to recognize in the limb buds a series of parallel bands of muscle tissue, extending longitudinally along the bud and each supplied by a definite segmental nerve. And furthermore, corresponding to each band upon the ventral (praeaxial) surface of the limb bud, there is a band similarly innervated upon the dorsal (postaxial) surface, since the fibers which pass to the limb from each nerve root sooner or later arrange themselves in praeaxial and postaxial
groups as is shown in the diagram Fig. 123. The first nerve which enters the limb bud lies along its anterior border, and consequently the muscle bands which are supplied by it will, in the adult, lie along
Fig. 124.  -  External Surface of the Os Innominatum showing the Attachment
of Muscles and the Zones Supplied by the Various Nerves.
12, Twelfth thoracic nerve; I to V, lumbar nerves; 1 and 2, sacral nerves.  -  (Bolk.)
the outer side of the arm and along the inner side of the leg, in consequence of the rotation in opposite directions which the limbs undergo during development (see p. 101).
The first nerve which supplies the muscles attached to the dorsum of the ilium is the second lumbar, and following that there come successively from before backward the remaining lumbar and the
Fig. 125.  -  Sections through (A) the Thigh and (B) the Calf showing the Zones Supplied by the Nerves. The Nerves are Numbered in Continuation with the Thoracic Series.  -  (A, after Bolk.)
first and second sacral nerves. The arrangement of the muscle bands supplied by these nerves and the muscles of the adult to which they contribute may be seen from Fig. 124. What is shown there is only the upper portions of the postaxial bands, their lower portions
extending downward on the anterior surface of the leg. Only the sacral bands, however, extend throughout the entire length of the limb into the foot, the second lumbar band passing down only to about the middle of the thigh, the third to about the knee, the fourth to about the middle of the crus and the fifth as far as the base of the fifth metatarsal bone, and the same is true of the corresponding praeaxial bands, which descend from the ventral surface of the os coxae (innominatum) along the inner and posterior surfaces of the leg to the same points. The first and second sacral bands can be traced into the foot, the first giving rise to the musculature of its
Fig. 126.  -  Section through the Upper Part of the Arm showing the Zones Supplied by the Nerves.
$v to jv, Ventral branches; 5J to Sd, dorsal branches of the cervical nerves. -  (Bolk.)
inner side and the second to that of its outer side, the praeaxial bands forming the plantar musculature, while the postaxial ones are upon the dorsum of the foot as a result of the rotation which the limb has undergone.
In a transverse section through a limb at any level all the muscle bands, both praeaxial and postaxial, which descend to that level will be cut and will lie in a definite succession from one border of the limb to the other, as is seen in Fig. 125. In the differentiation of the individual muscles which proceeds as the nerves extend from the trunk into the axial mesenchyme of the limb, the muscle bands
undergo modifications similar to those already described as occurring in the trunk myotomes. Thus, each of the muscles represented in Fig. 125, B, is formed by the fusion of elements derived from two or more bands; the soleus and gastrocnemius represent deep and superficial layers formed from the same bands by a horizontal (tangential) splitting, these same muscles contain a portion of the second sacral band which overlaps muscles composed only of higher myotomes, and the intermuscular septum between the peroneus brevis and the flexor hallucis longus represents a portion of the third sacral band which has degenerated into connective tissue.
A similar arrangement occurs in the bands which are to be recognized in the musculature of the upper limb. These are supplied by the fourth, fifth, sixth, seventh and eighth cervical and the first thoracic nerves, and only those supplied by the eighth cervical and the first thoracic nerves extend as far as the tips of the fingers. The arrangement of the bands in the upper part of the brachium may be seen from Fig. 126, in connection with which it must be noted that the fourth cervical band does not extend down to the level at which the section is taken and that the praeaxial band of the eighth cervical nerve and both the praeaxial and postaxial bands of the first thoracic are represented only by connective tissue in this region.
In another sense than the longitudinal one there is a division of the limb musculature into more or less definite areas, namely, in a transverse direction in accordance with the jointing of the skeleton. Thus, there may be recognized a group of muscles which pass from the axial skeleton to the pectoral girdle, another from the limb girdle to the brachium or thigh, another from the brachium or thigh to the antibrachium or crus, another from the antibrachium or crus to the carpus or tarsus, and another from the carpus or tarsus to the digits. This transverse segmentation, if it may be so termed, is not, however, perfectly definite, many muscles, even in the lower vertebrates, passing over more than one joint, and in the mammalia, especially, it is further obscured by secondary migrations, by the partial degeneration of muscles and by an end to end union of primarily distinct muscles.
The latissimus dorsi, serratus anterior and pectoral muscles are all examples of a process of migration as is shown by their innervation from cervical nerves, as well as by the actual migration which has been traced in the developing embryo (Mall, Lewis). In the lower limb evidences of migration may be seen in the femoral head of the biceps, comparative anatomy showing this to be a derivative of the gluteal set of muscles which has secondarily become attached to the femur and has associated itself with a praeaxial muscle to form a compound structure. An appearance of migration may also be produced by a muscle making a secondary attachment below its original origin or above the insertion and the upper or lower part, as the case may be, then degenerating into connective tissue. This has been the case with the peroneus longus, which, in the lower mammals, has a femoral origin, but has in man a new origin from the fibula, its upper portion being represented by the fibular lateral ligament of the knee-joint. So too the pectoralis minor is primarily inserted into the humerus, but it has made a secondary attachment to the coracoid process, its distal portion forming a coraco-humeral ligament.
The comparative study of the flexor muscles of the antibrachial and crural regions has yielded abundant evidence of extensive modifications in the differentiation of the limb muscles. In the tailed amphibia these muscles are represented by a series of superposed layers, the most superficial of which arises from the humerus or femur, while the remaining ones take their origin from the ulna or fibula and are directed distally and laterally to be inserted either into the palmar or plantar aponeurosis, or, in the case of the deeper layers, into the radius (tibia) or carpus (tarsus). In the arm of the lower mammalia the deepest layer becomes the pronator quadratus, the lateral portions of the superficial layer are the flexor carpi ulnaris and the flexor carpi radialis, while the intervening layers, together with the median portion of the superficial one, assuming a more directly longitudinal direction, fuse to form a common flexor mass which acts on the digits through the palmar aponeurosis. From this latter structure and from the carpal and metacarpal bones five
layers of palmar muscles take origin. The radial and ulnar portions of the most superficial of these become the flexor pollicis brevis and abductor pollicis brevis and the abductor quinti digiti, while the rest of the layer degenerates into connective tissue, forming tendons
Fig. 127.  -  Transverse sections through (A) the forearm and (B) the hand showing the arrangement of the layers of the flexor muscles. The superficial layer is shaded horizontally, the second layer vertically, the third obliquely to the left, the fourth vertically, and the fifth obliquely to the right. AbM, abductor digiti quinti; AdP, adductor pollicis; BR, brachio-radialis; ECD, extensor digitorum communis; ECU, extensor carpi ulnaris;£Z, extensor indicis; EMD, extensor digiti quinti; EMP, abductor pollicis longus; ERB, extensor carpi radialis brevis; FCR, flexor carpi radialis; FCU, flexor carpi ulnaris; FLP, flexor pollicis longus; FM, flexor digiti quinti brevis; FP, flexor digitorum profundus; FS, flexor digitorum sublimis; ID, interossei dorsales; IV, interossei volares; L, lumbricales; OM, opponens digiti quinti; PL, palmaris longus; PT, pronator teres; R, radius; U, ulna; II-V, second to fifth metacarpal.
which pass to the four ulnar digits. Gradually superficial portions of the antibrachial flexor mass separate off, carrying with them the layers of the palmar aponeurosis from which the tendons representing
the superficial layer of the palmar muscles arise, and they form with these the flexor digitorum sublimis. The deeper layers of the antibrachial flexor mass become the flexor digitorum profundus and the flexor pollicis longus (Fig. 127, A), and retain their connection with the deeper layers of the palmar aponeurosis which form their tendons; and since the second layer of the palmar muscles takes origin from this portion of the aponeurosis it becomes the lumbrical muscles, arising from the profundus tendons (Fig. 127,
Fig. 128.  -  Transverse sections through (A) the crus and (B) the foot, showing the arrangement of the layers of the flexor muscles. The shading has the same significance as in the preceding figure. AbH, abductor hallucis; AbM, abductor minimi digiti; AdH, adductor hallucis; ELD, extensor longus digitorum; F, fibula; FBD, flexor brevis digitorium; FBH, flexor brevis hallucis; FBM, flexor brevis minimi digiti; FLD, flexor longus digitorum; G, gastrocnemius; ID, interossei dorsalis; IV, interossei ventrales; L, lumbricales; P, plantaris; Pe, peroneus longus; Po, popliteus; S, soleus; T, tibia; TA, tibialis anticus; TP, tibialis posticus; I-V, first to fifth metatarsal.
B). The third layer of palmar muscles becomes the adductors of the digits, reduced in man to the adductor pollicis, while from the two deepest layers the interossei are developed. Of these the fourth layer consists primarily of a pair of slips corresponding to each digit, while the fifth is represented by a series of muscles which extend obliquely across between adjacent metacarpals. With these last muscles certain of the fourth layer slips unite to form the dorsal interossei, while the rest become the volar interossei. j The modifications of the almost identical primary arrangement in the crus and foot are somewhat different. The superficial layer
of the crural flexors becomes the gastrocnemius and plantaris (Fig. 128, A) and the deepest layer becomes the popliteus and the interosseous membrane. The second and third layers unite to form a common mass which is inserted into the deeper layers of the plantar aponeurosis and later differentiates into the soleus and the long digital flexor, the former shifting its insertion from the plantar aponeurosis to the os calcis, while the flexor retains its connection with the deeper layers of the aponeurosis, these separating from the superficial layer to form the long flexor tendons. The fourth layer partly assumes a longitudinal direction and becomes the tibialis posterior and the flexor hallucis longus and partly retains its original cblique direction and its connection with the deep layers of the plantar aponeurosis, becoming the quadratus plantse. In the foot (Fig. 128, B) the superficial layer persists as muscular tissue, forming the abductors, the flexor digitorum brevis and the medial head of the flexor hallucis brevis, the second layer becomes the lumbricales, and the third the lateral head of the flexor hallucis brevis and the adductor hallucis, while the fourth and fifth layers together form the ioterossei, as in the hand, the flexor quinti digiti brevis really belonging to that group of muscles.
C. R. Bardeen and W. H. Lewis: "Development of the Limbs, Body-wall, and
Back in Man," The American Journal of Anat., 1, 1901. K. Bardeleben: "Musk el und Fascia," Jenaische Zeitschr. fiir Naturwissensch.,
xv, 1882. L. Bolk: "Beziehungen zwischen Skelett, Muskulatur und Nerven der Extremitaten,
dargelegt am Beckengurtel, an dessen Muskulatur sowie am Plexus lumbo
sacralis," Morphol. Jahrbuch, xxi, 1894. L. Bolk: " Rekonstruktion der Segmentirung der Gliedmassenmuskulatur dargelegt
an den Muskeln des Oberschenkels und des Schultergurtels," Morphol. Jahrbuch,
xxii, 1895. L. Bolk: "Die Sklerozonie des Humerus," Morphol. Jahrbuch, xxill, 1S96. L. Bolk: "Die Segmentaldifferenzierung des menschlichen Rumpfes und seiner
Extremitaten," 1, Morphol. Jahrbuch, xxv, 1898. R. Futamtjra: "Ueber die Entwickelung der Facialismuskulatur des Menschen,"
Anat. Hefte, xxx, 1906. E. Godlewski: "Die Entwicklung des Skelet- und Herzmuskelgewebes der Sauge
thiere," Archiv fur mikr. Anat., lx, 1902.
E. Grafenberg: "Die Entwicklung der menschlichen Beckenmuskulatur," Anal.
Hefte, xxiii, 1904. W. P. Herringham: "The Minute Anatomy of the Brachial Plexus," Proceedings
of the Royal Soc. London, xli, 1886. W. H. Lewis: " The Development of the Arm in Man," Amer. Jour, of Anat., 1, 1902 J. B. MacCallum: "On the Histology and Histogenesis of the Heart Muscle-cell,"
Anat. Anzeiger, xiil, 1897. J. B. MacCallum: "On the Histogenesis of the Striated Muscle-fiber and the
Growth of the Human Sartorius Muscle," Johns Hopkins Hospital Bulletin, 1898
F. P. Mall: "Development of the Ventral Abdominal Walls in Man," Journ. of
Morphol., xiv, 1898. Caroline McGill: "The Histogenesis of Smooth Muscle in the Alimentary Canal
and Respiratory Tract of the Pig," Internat. Monatschr. Anat. und Phys., xxiv,
1907. J. P. McMurrich: "The Phylogeny of the Forearm Flexors," Amer. Journ, of Anat.,
11, 1903. J. P. McMurrich: "The Phylogeny of the Palmar Musculature," Amer. Journ. of
Anat., 11, 1903. J. P. McMurrich: "The Phylogeny of the Crural Flexors," Amer. Journ. of Anat.,
iv, 1904. J. P. McMurrich: "The Phylogeny of the Plantar Musculature," Amer. Journ. of
Anat., vi, 1907.
A. Meek: "Preliminary Note on the Post-embryonal History of Striped Muscle-fibers
in Mammalia," Anat. Anzeiger, xiv, 1898. (See also Anat. Anzeiger, xv, 1899.)
B. Morpurgo: "Ueber die post-embryonale Entwickelung der quergestreiften Muskel
von weissen Ratten," Anat. Anzeiger, xv, 1899. I. Popowsky: " Zur Entwicklungsgeschichte des N. facialis beim Menschen," Morphol.
Jahrbuch, xxiii, 1896. I. Popowsky: " Zur Entwickelungsgeschichte der Dammmuskulatur beim Menschen,"
Anat. Hefte, xi, 1899. L. Rethi: "Der peripheren Verlauf der motorischen Rachen- und Gaumennerven,"
Sitzungsber. der kais. Akad. Wissensch. Wien. Math.-Naturwiss. Classe, Cii, 1893.
C. S. Sherrington: " Notes on the Arrangement of Some Motor Fibers in the Lumbo
sacral Plexus," Journal of Physiol., xin, 1892. J. B. Sutton: "Ligaments, their Nature and Morphology," London, 1897.
At present nothing is known as to the earliest stages of development of the circulatory system in the human embryo, but it may be supposed that they resemble in their fundamental features what has been observed in such forms as the rabbit and the chick. In both these the system originates in two separate parts, one of which, located in the embryonic mesoderm, gives rise to the heart, while the other, arising in the extra-embryonic mesoderm, forms the first blood-vessels. It will be convenient to consider these two parts separately, and the formation of the blood-vessels may be first described.
In the rabbit the extension of the mesoderm from the embryonic region, where it first appears, over the yolk-sac is a gradual process, and it is in the more peripheral portions of the layer that the bloodvessels first make their appearance. They can be distinguished before the splitting of the mesoderm has been completed, but are always developed in that portion of the layer which is most intimately associated with the yolk-sac, and consequently becomes the splanchnic layer. They belong, indeed, to the deeper portion of that layer, that nearest the endoderm of the yolk-sac, and so characteristic is their origin from this portion of the layer that it has been termed the angioblast and has been held to be derived from the endoderm independently of the mesoderm proper. The first indication of blood-vessels is the appearance in the peripheral portion of the mesoderm of cords or minute patches of spherical cells (Fig. 129, .4). These increase in size by the division and separation of the cells from one another (Fig. 129, B), a clear fluid appearing in the intervals which separate them. Soon the cells surrounding each cord arrange
themselves to form an enclosing wall, and the cords, increasing in size, unite together to form a network of vessels in which float the spherical cells which may be known as mesamceboids (Minot). Viewed from the surface at this stage a portion of the vascular area of the mesoderm would have the appearance shown in Fig. 130, revealing a dense network of canals in which, at intervals, are groups of mesamaeboids adherent to the walls, constituting what have been termed the blood-islands, while in the meshes of the network unaltered mesoderm cells can be seen, forming the so-called substance-islands.
Fig. 129.  -  Transverse Section through the Area Vasculosa of Rabbit Embryos showing the Transformation of Mesoderm cells into the Vascular Cords.
Ec, Ectoderm; En, endoderm; Me, mesoderm.  -  (van der Stricht.)
At the periphery of the vascular area the vessels arrange themselves to form a sinus terminalis enclosing the entire area, and the vascularization of the splanchnic mesoderm gradually extends toward the embryo. Reaching it, the vessels penetrate the embryonic tissues and eventually come into connection with the heart, which has already differentiated and has begun to beat before the connection with the vessels is made, so that when it is made the circulation is at once established. Before, however, the vascularization reaches the embryo some of the canals begin to enlarge (Fig.
131,-4), producing arteries and veins, the rest of the network forming capillaries uniting these two sets of vessels, and, this process continuing, there are eventually differentiated a single vitelline artery and two vitelline veins (Fig. 131, B).
In the human embryo the small size of the yolk-sac permits of the extension of the vascular area over its entire surface at an early period, and this condition has already been reached in the earliest stages known and consequently no sinus terminalis such as occurs in the rabbit is visible. Otherwise the conditions are probably similar to what has been described above, the first circulation developed being associated with the yolk-sac.
It is to be noted that the capillary network of the area vasculosa consists of relatively wide anastomosing spaces whose endothelial lining rests directly upon the substance islands (Fig. 130). In certain of the embryonic organs, notably the liver, the metanephros and the heart, the network has a similar character, consisting of wide anastomosing spaces bounded by an endothelium which rests directly, or almost so, upon the parenchyma of the organ (the hepatic cylinders, the mesonephric tubules, or the cardiac muscle trabecular) (Figs. 132 and 190, B). To this form of capillary the term sinusoid has been applied (Minot), and it appears to be formed by the expansion of the wall of a previously existing blood-vessel, which thus moulds itself, as it were, over the parenchyma of the organ. The
Fig. 130.  -  Surface View of a Portion of the Area Vasculosa of a Chick.
The vascular network is represented by the shaded portion. Bi, Bloodisland; Si, substance-island.  -  (Disse.)
true capillaries, on the other hand, are more definitely tubular in form, are usually imbedded in mesenchymatous connective tissue and are developed in the same manner as the primary capillaries of the area vasculosa, by the aggregation of vasifactive cells to form cords, and the subsequent hollowing out of these. Whether these vasifactive cells are new differentiations of the embryonic mesenchyme or are budded off from the walls of existing capillaries which have grown in from extra-embryonic regions, is at present undecided. The Formation of the Blood.  -  The mesamceboids, which are
i i
A , \
Fig. 131.  -  The Vascular Areas of Rabbit Embryos. In B the Veins are Represented by Black and the Network is Omitted.  -  (van Beneden and Julin.)
the first formed blood-corpuscles are all nucleated and destitute or nearly so of haemoglobin. They have been held by some observers to be the only source of the various forms of corpuscles that are found in the adult vessels, while others maintain that they give rise only to the red corpuscles, the leukocytes arising in tissues external to the blood-vessels and only secondarily making their way into them. According to this latter view the red and white corpuscles have a different origin and remain distinct throughout life.
So long as the formation of blood-vessels is taking place in the extra-embryonic mesoderm, so long are new mesamceboids being differentiated from the mesoderm. But whether the formation of blood-vessels within the embryo results from a differentiation of the embryonic mesoderm in situ, or from the actual ingrowth of vessels from the extra-embryonic regions (His), is as yet uncertain, and hence it is also uncertain whether mesamceboids are differentiated from the embryonic mesoderm or merely pass into the embryonic region from the more peripheral areas. However this may be, it is certain that they and the erythrocytes that are formed from them increase by division in the interior of the embryo, and that there are certain portions of the body in which these divisions take place most abundantly, partly, perhaps, on account of the more favorable conditions of nutrition which they present and partly because they are regions where the circulation is sluggish and permits the accumulation of erythrocytes. These regions constitute what have been termed the hematopoietic organs, and are especially noticeable in the later stages of fetal life, diminishing in number and variety about the time of birth. It must be remembered, however, that the life of individual corpuscles is comparatively short, their death and disintegration taking place continually during the entire life of the individual, so that there is a necessity for the formation of new corpuscles and for the existence of haematopoietic organs at all stages of life.
In the fetus mesamceboids in process of division may be found in the general circulation and even in the heart itself, but they are much more plentiful in places where the blood-pressure is diminished, as, for instance, in the larger capillaries of the lower limbs and in the capillaries of all the visceral organs and of the subcutaneous tissues. Certain organs, however, such as the liver, the spleen, and the bone-marrow, present especially favorable conditions for the multiplication of the blood-cells, and in these not only are the capillaries enlarged so as to afford resting-places for the corpuscles, but gaps appear in the walls of the vessels through which the blood-elements may pass and so come into intimate relations with the actual tissues is
of the organs (Fig. 132). After birth the haematopoietic function of the liver ceases and that of the spleen becomes limited to the formation of white corpuscles, though the complete function may be re-established in cases of extreme anaemia. The bone-marrow, however, retains the function completely, being throughout life the seat of formation of both red and white corpuscles, the lymphatic nodes and follicles, as well as the spleen, assisting in the formation of the latter elements.
The mesamceboids early become converted into nucleated red
corpuscles or erythrocytes by the development of haemoglobin in their cytoplasm, their nuclei at the same time becoming granular. Up to a stage at which the embryo has a length of about 12 mm. these are the only form of red corpuscle in the circulation, but at this time (Minot) a new form, characterized by its smaller size and more deeply staining nucleus, makes its appearance. These erythrocytes have been termed normoblasts (Ehrlich), although they are merely transition stages leading to the formation of erythroplastids by the extrusion of their nuclei (Fig. 133). The cast-off nuclei undergo degeneration and phagocytic absorption by the leukocytes, and the masses of cytoplasm pass into the circulation, becoming more and more numerous as development proceeds, until finally they are the typical haemoglobin-containing elements in the blood and form what are properly termed the red bloodcorpuscles.
It has already (p. 224) been pointed out that discrepant views
Fig. 132.  -  Section of a Portion or the Liver of a Rabbit Embryo of 5 mm. e, Erythrocytes in the liver substance and in a capillary; h, hepatic cells.  -  (van der Stricht)
prevail as to the origin of the white blood-corpuscles. Indeed, three distinct modes of origin have been assigned to them. According to one view they have a common origin with the erythrocytes from the mesamceboids (Weidenreich), according to another they are formed from mesenchyme cells outside the cavities of the blood-vessels (Maximo w), while according to a third view the first formed leukocytes take their origin from the endodermal epithelial cells of the thymus gland (Prenant).
But whatever may be their origin in later stages the leukocytes multiply by mitosis and there is a tendency for the dividing cells to collect in the lymphoid tissues, such as
the lymph nodes, tonsils, etc., to form /||\ /^s 0$\ /^p. & more or less definite groups which  -  ^^ v^ KjJ \Jj
have been termed germ-centers (Flem
. m , .. . . _ Fig. 133.  -  Stages in the
ming). The new cells when they first transformation of an Ery
pass into the circulation have a rel- throcyte into an _ Erythro
r plastid.  -  (van der Stricnt.)
atively large nucleus surrounded by a
small amount of cytoplasm without granules and, since they resemble the cells found in the lymphatic vessels, are termed lymphocytes (Fig. 134, a). In the circulation, however, other forms of leukocytes also occur, which are believed to have their origin from cells with much larger nuclei and more abundant cytoplasm, which occur throughout life in the bone-marrow and have been termed myelocytes. Cells of a similar type, free in the circulation, constitute what are termed the finely granular leukocytes (neutrophile cells of Ehrlich) (Fig. 134, b), but whether these and the myelocytes are derived from lymphocytes or have an independent origin is as yet undetermined. Less abundant are the coarsely granular leukocytes (eosinophile cells of Ehrlich) (Fig. 134, c), characterized by the coarseness and staining reactions of their cytoplasmic granules and by their reniform or constricted nucleus. They are probably derivatives of the finely granular type and it has been maintained by Weidenreich that their granules have been acquired by the phagocytosis of degenerated erythrocytes. Finally, a third type is formed by the polymorphonuclear or polynuclear leukocytes (basophile cells
of Ehrlich) (Fig. 134, d), which are to be regarded as leukocytes in the process of degeneration and are characterized by their irregularly lobed or fragmented nuclei, as well as by their staining peculiarities.
In the fetal haematopoietic organs and in the bone-marrow of the adult large, so-called giant-cells are found, which, although they do not enter into the general circulation, are yet associated with the development of the blood-corpuscles. These giant-cells as they
Fig. 134.  -  Figures of the Different Forms of White Corpuscles occurring
in Human Blood.
a, Lymphocytes; b, finely granular (neutrophile) leukocyte; c, coarsely granular (eosino
phile) leukocyte; d, polymorphonuclear (basophile) leukocyte.  -  (Weidenreich.)
occur in the bone-marrow are of two kinds which seem to be quite distinct, although both are probably formed from leukocytes. In one kind the cytoplasm contains several nuclei, wherce they have been termed polycaryocytes, and they seem to be the cells which have already been mentioned as osteoclasts (p. 158). In the other kind (Fig- I 35) tne nucleus is single, but it is large and irregular in shape, frequently appearing as if it were producing buds. These megacaryocytes appear to be phagocytic cells, having as their function the destruction of degenerated corpuscles and of the nuclei of the erythrocytes.
The blood-platelets have recently been shown by Wright to be formed from the cytoplasm of the megacaryocytes, by the constriction and separation of portions of the slender processes to which they give rise in their amoeboid movements (Fig. 135).
Fig. 135.  -  Megacaryocyte from a Kitten, which has Extended two pseudopodial processes through the wall of blood-vessel and is budding off blood-platelets.
bp, Blood-platelets; V, blood-vessel.  -  (J. H. Wright.)
The Formation of the Heart.  -  The heart makes its appearance while the embryo is still spread out upon the surface of the yolk-sac, and arises as two separate portions which only later come into contact in the median line. On each side of the body near the margins of the embryonic area a fold of the splanchnopleure appears, projecting into the ccelomic cavity, and within this fold a very thinwalled sac is formed, probably by a splitting off of its innermost cells (Fig. 136, .4). Each fold will produce a portion of the muscular walls (myocardium) of the heart, and each sac part of its endothelium (endocardium). As the constriction of the embryo from the yolk-sac proceeds, the two folds are gradually brought nearer together (Fig. 136, B), until they meet in the mid-ventral line, when the myocardial folds and endocardial sacs fuse together (Fig. 136, C) to form a cylindrical heart lying in the mid-ventral line of the body, in front of the anterior surface of the yolk-sac and in what will later be the
cervical region of the body. At an early stage the various veins which have already been formed, the vitellines, umbilicals, jugulars
Fig. 136.  -  Diagrams Illustrating the Formation or the Heart in the
Guinea-pig. The mesoderm is represented in black and the endocardium by a broken line. am, Amnion; en, endoderm; h, heart; i, digestive tract.-  -  (After Strahl and Carius.)
and cardinals, unite together to open into a sac-like structure, the sinus venosus, and this opens into the posterior end of the heart cylinder. The anterior end of the cylinder tapers off to form the
aortic bulb, which is continued forward on the ventral surface of the pharyngeal region and carries the blood away from the heart. The blood accordingly opens into the posterior end of the heart tube and flows out from its anterior end.
The simple cylindrical form soon changes, however, the heart tube in embryos of 2.15 mm. in length having become bent upon itself into a somewhat S-shaped curve (Fig. 137). Dorsally and to the left is the end into which the sinus venosus opens, and from this
Fig. 137.  -  Heart of EmbrycTof 2.15 mm., from a Reconstruction.
a, Atrium; ab, aortic bulb; d, diaphragm; dc, ductus Cuvieri; /, liver; v, ventricle; vj, jugular vein; vu, umbilical vein.  -  (His.)
Fig. 138.  -  Heart of Embryo of 4.2 mm., seen from the Dorsal Surface.
DC, Ductus Cuvieri; I A , left atrium rA, right atrium; vf, jugular vein; VI, left ventricle; vu, umbilical vein.  -  (His.)
the heart tube ascends somewhat and then bends so as to pass at first ventrally and then caudally and to the right, where it again bends at first dorsally and then anteriorly to pass over into the aortic bulb. The portion of the curve which lies dorsally and to the left is destined to give rise to both atria, the portion which passes from right to left represents the future left ventricle, while the succeeding portion represents the right ventricle. In later stages (Fig. 138) the left ventricular portion drops downward in front of the atrial
portion, assuming a more horizontal position, while the portion which represents the right ventricle is drawn forward so as to lie in the same plane as the left.
At the same time two small out-pouchings develop from the atrial part of the heart and form the first indications of the two atria. As development progresses, these increase in size to form large pouches opening into a common atrial canal (Fig. 139) which is directly continuous with the left ventricle, and as the enlargement of the pouches continues their openings into the canal enlarge,
until finally the pouches become continuous with one another, forming a single large sac, and the atrial canal becomes reduced to a short tube which is slightly invaginated into the ventricle (Fig. 140).
In the meantime the sinus venosus, which was originally an oval sac and opened into the atrial canal, has elongated transversely until it has assumed the form of a crescent whose convexity is in contact with the walls of the atria, and its opening into the heart has verged toward the right, until it is situated entirely within the area of the right atrium. As the enlargement of the atria continues, the right horn and median portion of the crescent are gradually taken up into their walls, so that the various veins which originally opened into the sinus now open directly into the right atrium by a single opening, guarded by a projecting fold which is continued upon the roof of the atrium as a muscular ridge known as the septum spurium (Fig. 140, sp). The left horn of the crescent is not taken up into the atrial wall, but remains upon its posterior surface as an elongated sac forming the coronary sinus.
The division of the now practically single atrial cavity into the
Fig. 139.  -  Heart of Embryo of 5 mm., Seen from in Front and slightly from Above.  -  (His).
permanent right and left atria begins with the formation of a falciform ridge running dorso-ventrally across the roof of the cavity. This is the atrial septum or septum primum (Fig. 140, ss), and it rapidly increases in size and thickens upon its free margin, which reaches almost to the upper border of the short atrial canal (Fig. 142). The continuity of the two atria is thus almost dissolved, but is soon re-established by the formation in the dorsal part of the septum of an opening which soon reaches a considerable size and is known as
Fig. 140.  -  Inner Surface of the Heart of an Embryo of 10 mm.
al, Atrio-ventricular thickening; sp, septum spurium; ss, septum primum; sv, septum
ventriculi; ve, Eustachian valve.  -  (His.)
the foramen ovale (Fig. 141, fo). Close to the atrial septum, and parallel with it, a second ridge appears in the roof and ventral wall of the right atrium. This septum secundum (Fig. 141, S 2 ) is of relatively slight development in the human embryo, and its free edge, arching around the ventral edge and floor of the foramen ovale, becomes continuous with the left lip of the fold which guards the opening of the sinus venosus and with this forms the annulus of Vieussens of the adult heart.
Si Sz
When the absorption of the sinus venosus into the wall of the right atrium has proceeded so far that the veins communicate directly with the atrium, the vena cava superior opens into it at the upper part of the dorsal wall, the vena cava inferior more laterally, and below this is the smaller opening of the coronary sinus. The
upper portion of the right lip of the fold which originally surrounded the opening of the sinus venosus, together with the septum spurium, gradually disappears; the lower portion persists, however, and forms (i) the Eustachian valve (Fig. 141, Ve), guarding the opening of the inferior cava and directing the blood entering by it toward the foramen ovale, and (2) the Thebesian valve, which guards the opening of the coronary sinus. At first no Fig. 141. -  Heart of Embryo veins communicate with the left atrium,
OF I0.2 CM. FROM WHICH HALF , 111 c t i 1
of the Right Auricle has but on the development of the lungs and been Removed. the establishment of their vessels, the
fo, Foramen ovale; pa, pul- , . .,,
monary artery; S u septum pri- pulmonary veins make connection with
mum; S 2 ,_ septum secundum; j t TwQ ye j ns arise from eac h l ung an( J ba, systemic aorta; V, right ven- °
tricle; vd and vcs, inferior and as they pass toward the heart they unite
superior venae cavae; Ve, Eusta- ,-, i r „ j •
chfan valve. . in pairs, the two vessels so formed again
uniting to form a single short trunk which opens into the upper part of the atrium (Fig. 142, Vep). As is the case with the right atrium and the sinus venosus, the expansion of the left atrium brings about the absorption of the short single trunk into its walls, and, the expansion continuing, the two vessels are also absorbed, so that eventually the four primary veins open independently into the atrium.
While the atrial septa have been developing there has appeared on the dorsal wall of the atrial canal a tubercle-like thickening of the endocardium, and a similar thickening also forms on the ventral wall. These endocardial cushions increase in size and finally unite together by their tips, forming a complete partition, dividing the
2 35
atrial canal into a right and left half (Fig. 142). With the upper edge of this partition the thickened lower edge of the atrial septum unites, so that the separation of the atria would be complete were it not for the foramen ovale.
Fig. 142.  -  Section through a Reconstruction of the Heart of a Rabbit
Embryo of 10. i mm. Ad and Ad u Right and As, left atrium; Bw x and Bw 2 , lower ends of the ridges which divide the aortic bulb; En, endocardial cushion; En.r and En.s, thickenings of the cushion; la, interatrial and Iv, interventricular communication; S v septum primum; Sd, right and Ss, left horn of the sinus venosus; S.iv, ventricular septum; SM, opening of the sinus venosus into the atrium; Vd, right and Vs, left ventricle; Vej, jugular vein; Vep, pulmonary vein; Vvd and Vvs, right and left limbs of the valve guarding the opening of the sinus venosus.  -  (Born.)
While these changes have been taking place in the atrial portion of the heart, the separation of the right and left ventricles has also been progressing, and in this two distinct septa take part. From the floor of the ventricular cavity along the line of junction of the
right and left portions a ridge, composed largely of muscular tissue, arises (Figs. 140 and 142), and, growing more rapidly in its dorsal than its ventral portion, it comes into contact and fuses with the dorsal part of the partition of the atrial canal. Ventrally, however, the ridge, known as the ventricular septum, fails to reach the ventral part of the partition , so that an oval foramen, situated just below the point where the aortic bulb arises, still remains between the two ventricles. This opening is finally closed by what it termed the aortic septum. This makes its appearance in the aortic bulb just at the point where the first lateral branches which give origin to the pulmonary arteries (see p. 243) arise, and is formed by the fusion of the free edges of two endocardial ridges which develop on opposite sides of the bulb. From its point of origin it gradually extends down the bulb until it reaches the ventricle, where it fuses with the free edge of the ventricular septum and so completes the separation of the two ventricles (Fig. 143). The bulb now consists of two vessels lying side by side, and owing to the position of the partition at its anterior end, one of these vessels, that which opens into the right ventricle, is continuous with the pulmonary arteries, while the other, which opens into the left ventricle, is continuous with the rest of the vessels which arise from the forward continuation of the bulb. As soon as the development of the partition is completed, two grooves, corresponding in position to the lines of attachment of the partition on the inside of the bulb, make their appearance on the outside and gradually deepen until they finally meet and divide the bulb into two separate vessels, one of which is the pulmonary aorta and the other the systemic aorta.
In the early stages of the heart's development the muscle bundles which compose the wall of the ventricle are very loosely arranged, so that the ventricle is a somewhat spongy mass of muscular tissue with a relatively small cavity. As development proceeds the bundles nearest the outer surface come closer together and form a compact layer, those on the inner surface, however, retaining their loose arrangement for a longer time (Fig. 142). The lower edge of the atrial canal becomes prolonged on the left side into one, and on the
right side into two, flaps which project downward into the ventricular cavity, and an additional flap arises on each side from the lower
Fig. 143.  -  Diagrams of Sections through the Heart of Embryo Rabbits to Show the Mode of Division of the Ventricles and of the Atrio-ventricular Orifice.
Ao, Aorta; Ar. p, pulmonary artery; B, aortic bulb; Bw 2 and *, one of the ridges which divide the bulb; Eo, and Eu, upper and lower thickenings of the margins of the atrio-ventricular orifice; F.av.c, the original atrio-ventricular orifice; F.av.d and F.av.s, right and left atrio-ventricular orifices; Oi, interventricular communication; S.iv, ventricular septum; Vd and Vs, right and left ventricles.  -  (Born.)
edge of the partition of the atrial canal, so that three flaps occur in the right atrio-ventricular opening and two in the left. To the
2 3 8
under surfaces of these flaps the loosely arranged muscular trabecular of the ventricle are attached, and muscular tissue also occurs in the flaps. This condition is transitory, however; the muscular tissue of the flaps degenerates to form a dense layer of connective tissue, and at the same time the muscular trabecular undergo a condensation. Some of them separate from the flaps, which represent the atrio-ventricular valves, and form muscle bundles which may fuse throughout their entire length with the more compact portions of the ventricular walls, or else may be attached only by their ends, forming loops; these two varieties of muscle bundles constitute the trabecule carnece of the adult heart. Other bundles
Fig. 144.  -  Diagrams showing the Development of the Atjriculo-ventricular
b, Muscular trabecule; cht, chordae tendinae; mk and vtk 1 , valve; pm, musculus papillaris;
tc, trabeculse carneae; v, ventricle.  -  (From Hertwig, after Gegenbaur.)
may retain a transverse direction, passing across the ventricular cavity and forming the so-called moderator bands; while others, again, retaining their attachment to the valves, condense only at their lower ends to form the musculi papillares, their upper portions undergoing conversion into strong though slender fibrous cords, the chorda tendinece (Fig. 144).
The endocardial lining of the ventricles is at first a simple sac separated by a distinct interval from the myocardium, but when the condensation of the muscle trabecular occurs the endocardium applies itself closely to the irregular surface so formed, dipping into all the crevices between the trabeculse carneae and wrapping itself around
the musculi papillares and chordae tendineae so as to form a complete
lining of the inner surface of the myocardium.
The aortic and pulmonary semilunar valves make their appearance,
before the aortic bulb undergoes its longitudinal splitting, as four
tubercle-like thickenings of connective tissue situated on the inner
wall of the bulb just where it arises from the ventricle. When the
division of the bulb occurs, two of the thickenings, situated on
opposite sides, are divided, so that both the
pulmonary and systemic aorta? receive three
thickenings (Fig. 145). Later the thickenings
become hollowed out on the surfaces directed
away from the ventricles and are so converted
into the pouch-like valves of the adult.
Changes in the Heart after Birth.  -  The T FlG - 145- -  Diagrams
/ . Illustrating the For
heart when first formed lies far forward in the mation of the Semi
neck region of the embryo, between the head £toarValves.-(G^«»and the anterior surface of the yolk-sac, and from this position it gradually recedes until it reaches its final position in the thorax. And not only does it thus change its relative position, but the direction of its axes also changes. For at an early stage the ventricles lie directly in front of (i. e., ventrad to) the atria and not below them as in the adult heart, and this primitive condition is retained until the diaphragm has reached its final position (see p. 322).
In addition to these changes in position, which are antenatal, important changes also occur in the atrial septum after birth. Throughout the entire period of fetal life the foramen ovale persists, permitting the blood returning from the placenta and entering the right atrium to pass directly across to the left atrium, thence to the left ventricle, and so out to the body through the systemic aorta (see p. 267). At birth the lungs begin to function and the placental circulation is cut off, so that the right atrium receives only venous blood and the left only arterial; a persistence of the foramen ovale beyond this period would be injurious, since it would permit of a mixture of the arterial and venous bloods, and, consequently, it
closes completely soon after birth. The closure is made possible by the fact that during the growth of the heart in size the portion of the atrial septum which is between the edge of the foramen ovale and the dorsal wall of the atrium increases in width, so that the foramen is carried further and further away from the dorsal wall of the atrium and comes to be almost completely overlapped by the annulus of Vieussens (Fig. 141). This process continuing, the dorsal portion of the atrial septum finally overlaps the free edge of the annulus, and after birth the fusion of the.overlapping surfaces takes place and the foramen is completely closed.
In a large percentage (25 to 30 per cent.) of individuals the fusion of the surfaces of the septum and annulus is not complete, so that a slit-like opening persists between the two atria. This, however, does not allow of any mingling of the blood in the two cavities, since when the atria contract the pressure of the blood on both sides will force the overlapping folds together and so practically close the opening. Occasionally the growth of the dorsal portion of the septum is imperfect or is inhibited, in which case closure of the foramen ovale is impossible.
The Development of the Arterial System.-  -  It has been seen (p. 221) that the formation of the blood-vessels begins in the extraembryonic splanchnic mesoderm surrounding the yolk-sac and extends thence toward the embryo. Furthermore, it has been seen that the vessels appear as capillary networks from which definite stems are later elaborated. This seems also to be the method of formation of the vessels developed within the body of the embryo, the arterial and venous stems being first represented by a number of anastomosing capillaries, from which, by the enlargement of some and the disappearance of the others, the definite stems are formed.
The earliest known embryo that shows a blood circulation is that described by Eternod (Fig. 43). From the plexus of vessels on the yolk-sack two veins arise which unite with two other veins returniDg from the chorion by the belly-stalk and passing forward to the heart as the two umbilical veins (Fig. 146, Vu). There is as yet no vitelline vein, the chorionic circulation in the human embryo apparently taking precedence over the vitelline. From the heart a short arterial stem arises, which soon divides so as to form three
branches* passing dorsally on either side of the pharynx. The branches of each side then unite to form a paired dorsal aorta (dAr, dAs) which extends caudally and is continued into the belly-stalk and so to the chorion as the umbilical arteries (Au). There is as yet no sign of vitelline arteries passing to the yolk-sack, again an indication of the subservience of the vitelline to the chorionic circulation in the human embryo.
Fig. 146.  -  Diagram showing the Arrangement of the Blood-vessels in an
Embryo 1.3 mm. in Length.
Au, Umbilical artery; All, allantois; Ch, chorionic villus; dAr and dAs, right and left
dorsal aortae; Vu, umbilical veins; Ys, yolk-sack.  -  (From Kollmann after Eternod.)
In later stages when the branchial arches have appeared the dorsally directed arteries are seen to lie in these, forming what are termed the branchial arch vessels, and later also the two dorsal
* Evans (Keibel-Mall, Human Embryology, Vol. 11, 1912) considers two of these branches to be probably plexus formations rather than definite stems, since there is evidence to indicate that only one such stem exists at such an early stage of development. 16
aortae fuse as far forward as the region of the eighth cervical segment to form a single trunk from which segmental branches arise.
It will be convenient to consider first the history of the vessels which pass dorsally in the branchial arches. Altogether, six of these vessels are developed, the fifth being rudimentary and transitory, and when fully formed they have an arrangement which may be understood from the diagram (Fig. 147). This arrangement represents a condition which is permanent in the lower vertebrates. In the fishes the respiration is performed by means of gills developed upon the branchial arches, and the heart is an organ which receives venous blood from the body and pumps it to the gills, in which it becomes arterialized and is then collected into the dorsal aortae, which distribute it to the body. But in terrestrial animals, with the loss of the gills and the development of the lungs as respiratory organs, the capillaries of the gills disappear and the afferent and efferent branchial vessels become continuous, the condition represented in the diagram resulting. But this condition is merely temporary in the mammalia and numerous changes occur in the arrangement of the vessels before the adult plan is realized. The first change is a disappearance of the vessel of the first arch, the ventral stem from which it arose being continued forward to form the temporal arteries, giving off near the point where the branchial vessel originally arose a branch which represents the internal maxillary artery in part, and possibly also a
Fig. 147.  -  Diagram Illustrating the Primary Arrangement of the Branchial Arch Vessels.
a, aorta; db, aortic bulb; ec, external carotid; ic, internal carotid; sc, subclavian; I-VI, branchial arch vessels.
second branch which represents the external maxillary (His). A little later the second branchial vessel also degenerates (Fig. 148), a branch arising from the ventral trunk near its former origin, possibly representing the future lingual artery (His), and then the portion of the dorsal trunk which intervenes between the third and fourth branchial vessels vanishes, so that the dorsal trunk anterior to the third branchial arch is cut off from its connection with the dorsal aorta and forms, together with the vessel of the third arch, the internal carotid, while the ventral trunk, anterior to the point of
Fig. 148.  -  Arteriat, System of an Embryo of 10 mm.
Ic, Internal carotid; P, pulmonary artery; Ve, vertebral artery; III to VI, persistent
branchial vessels.  -  (His.)
origin of the third vessel, becomes the external carotid, and the portion which intervenes between the third and fourth vessels becomes the common carotid (Fig. 149).
The rudimentary fifth vessel, like the first and second, disappears, but the fourth persists to form the aortic arch, there being at this stage of development two complete aortic arches. From the sixth vessel a branch arises which passes backward to the lungs, forming the pulmonary artery, and the portion of the vessel of the right side which intervenes between this and the aortic arch disappears, while the corresponding portion of the left side persists
until after birth, forming the ductus arteriosus (ductus Botalli) (Fig. 149). When the longitudinal division of the aortic bulb occurs (p. 236), the septum is so arranged as to place the sixth arch in communication with the right ventricle and the remaining vessels in connection with the left ventricle, the only direct communication
between the systemic and ec pulmonary vessels being by
way of the ductus arteriosus, whose significance will be explained later (p. 267).
One other change is still necessary before the vessels acquire the arrangement which they possess during fetal life, and this consists in the disappearance of the lower portion of the right aortic arch (Fig. 149), so that the left arch alone forms the connection between the heart and the dorsal aorta. The upper part of the right aortic arch persists to form the proximal part of the right subclavian artery, the portion of the ventral trunk which unites the arch with the aortic bulb becoming the innominate artery.
From the entire length of the thoracic aorta, and in the embryo from the aortic arches, lateral branches arise corresponding to each segment and accompanying the segmental nerves. The first of these branches arises just below the point of union of the vessel of the sixth arch with the dorsal trunk and accompanies the hypoglossal nerve (Fig. 150, h), and that which accompanies the seventh
Fig. 149.  -  Diagram Illustrating the changes in the branchial arch vessels.
a, Aorta; da, ductus arteriosus; ec, external carotid; ic, internal carotid; pa, pulmonary artery; sc, subclavian; I- VI, aortic arch vessels.
cervical nerve arises just above the point of union of the two aortic arches (Fig. 150, s), and extends out into the limb bud, forming the subclavian artery.*
Further down twelve pairs of lateral branches, arising from the thoracic portion of the aorta, represent the intercostal arteries, and still lower four pairs of lumbar arteries are formed, the fifth lumbars being represented by two large branches, the common iliacs, which seem from their size to be the continuations of the aorta rather than branches of it. The true continuation of the aorta is, however, the middle sacral artery, which represents in a degenerated form the caudal prolongation of the aorta of other mammals, and, like this, gives off lateral branches corresponding to the sacral segments.
In addition to the segmental FlG . I50 . -  diagram showing the Re
lateral branches arising from nations op the Lateral Branches to
the Aortic Arches.
the aorta, Visceral branches, EC> External carotid; h, lateral branch
Which have their origin rather cacompanying the hypoglossal nerve; IC,
° internal carotid; ICo, intercostal; IM, m
from the Ventral surface, also ternal mammary; s, subclavian; v, verte
^„„,,~ TV, ~™u„mr, ~t - mm bral; I to VIII, lateral cervical branches;
OCCUr. In embryos of 5 mm. I; 2) lateral thoracic branches.
these branches are arranged in
a segmental manner in threes, a median unpaired vessel passing to the digestive tract and a pair of more lateral branches passing to the mesonephros (see p. 339) corresponding to each of the paired branches passing to the body wall (Fig. 151). As
* It must be remembered that the right subclavian of the adult is more than equivalent to the left, since it represents the fourth branchial vessel + a portion of the dorsal longitudinal trunk + the lateral segmental branch (see Fig. 142).
development proceeds the great majority of these visceral branches disappear, certain of the lateral ones persisting, however, to form the renal, internal spermatic, and hypogastric arteries of the adult, while the unpaired branches are represented only by the c celiac artery and the superior and inferior mesenteries. The superior mesenteric artery is the adult representative of the vitelline artery of the embryo and arises from the aorta by two, three or more roots, which correspond to the fifth, fourth and higher thoracic
Fig. 151.  -  Diagram showing the Arrangement of the Segmental Branches
arising from the aorta. A, Aorta; B, lateral somatic branch; c, lateral visceral branch; D, median visceral
branch; E, peritoneum.
segments. Later, all but the lowest of the roots disappear and the persisting one undergoes a downward migration in accordance with the recession of the diaphragm and viscera (see p. 322), until in embryos of 17 mm. it lies opposite the first lumbar segment. Similarly the cceliac and inferior mesenteric arteries, which when first recognizable in embryos of 9 mm. correspond with the fourth and twelfth thoracic segments respectively, also undergo a secondary downward migration, the cceliac artery in embryos of 17 mm. arising
opposite the twelfth thoracic and the inferior mesenteric opposite the third lumbar segment.
The umbilical arteries of the embryo seem at first to be the direct continuations of the dorsal aortas (Fig. 146), but as development proceeds they come to arise from the aorta opposite the third lumbar segment, where they are in line with the lateral visceral segmental branches. They pass ventral to the Wolffian duct (see p. 339) and are continued out along with the allantois to the chorionic villi. Later this original stem is joined, not far from its origin, by what appears to be the lateral somatic branch of the fifth lumbar segment, whereupon the proximal part of the original umbilical vessel degenerates and the umbilical comes to arise from the somatic branch, which is the common iliac artery of adult anatomy (Fig. 152). Hence it is that this vessel in the adult gives origin both to branches such as the external iliac, the gluteal, the sciatic and the internal pudendal, which are distributed to the body walls
or their derivatives, and to others, such as the vesical, inferior haemorrhoidal and uterine, which are distributed to the pelvic viscera. At birth the portions of the umbilical arteries beyond the umbilicus are severed when the umbilical cord is cut, and their intra-embryonic portions, which have been called the hypogastric arteries, quickly undergo a reduction in size. Their proximal portions remain functional as the superior vesical arteries, carrying blood to the urinary bladder, but the portions which intervene between the
Fig. 152.  -  Diagram Illustrating the Development of the Umbilical Arteries.
A, Aorta; CIl, common iliac; Ell, external iliac; G, gluteal; III, internal iliac; IP, internal pudic; IV, inferior vesical; Sc, sciatic; U, umbilical; U', primary proximal portion of the umbilical; wd, Wolffian duct.
bladder and the umbilicus become reduced to solid cords, forming the obliterated hypogastric arteries of adult anatomy. f~ In its general plan, accordingly, the arterial system may be regarded as consisting of a pair of longitudinal vessels which fuse together throughout the greater portion of their length to form the dorsal aorta, from which there arise segmentary arranged lateral somatic branches and ventral and lateral visceral branches. With the exception of the aortic trunks (together with their anterior continuations, the internal carotids) and the external carotids, no longitudinal arteries exist primarily. In the adult, however, several longitudinal vessels, such as the vertebrals, internal mammary, and epigastric arteries, exist. The formation of these secondary longitudinal trunks is the result of a development between adjacent vessels of anastomoses, which become larger and more important blood-channels than the original vessels.
At an early stage each of the lateral branches of the dorsal aorta gives off a twig which passes forward to anastomose with a backwardly directed twig from the next anterior lateral branch, so as to form a longitudinal chain of anastomoses along each side of the neck. In the earliest stage at present known the chain starts from the lateral branch corresponding to the first cervical (suboccipital) segment and extends forward into the skull through the foramen magnum, terminating by anastomosing with the internal carotid. To this original chain other links are added from each of the succeeding cervical lateral branches as far back as the seventh (Figs. 150 and 153). But in the meantime the recession of the heart toward the thorax has begun, with the result that the common carotid stems are elongated and the aortic arches are apparently shortened so that the subclavian arises on the left side almost opposite the point where the aorta was joined by the sixth branchial vessel. As this apparent shortening proceeds, the various lateral branches which give rise to the chain of anastomoses, with the exception of the seventh, disappear in their proximal portions and the chain becomes an independent stem, the vertebral artery, arising from the seventh lateral branch, which is the subclavian.
The recession of the heart is continued until it lies below the level of the upper intercostal arteries, and the upper two of these, together with the last cervical branch on each side, lose their connection with the dorsal aorta, and, sending off anteriorly and posteriorly
Fig. 153.  -  The Development of the Vertebral Artery in a Rabbit Embryo
of Twelve Days.
IIIA.B to VIA.B, Branchial arch vessels; Ap, pulmonary artery. A.v.c.b and A.v.cv, cephalic and cervical portions of the vertebral artery; A.s, subclavian; C.d and C.v internal and external carotid ; ISp.G, spinal ganglion.  -  (Hochstetter.)
anastomosing twigs, develop a short longitudinal stem, the superior intercostal, which opens into the subclavian.
The intercostals and their abdominal representatives, the
lumbars and iliacs, also give rise to longitudinal anastomosing twigs near their ventral ends (Fig. 154), and these increasing in size give rise to the internal mammary and inferior epigastric arteries, which together form continuous stems extending from the subclavian to the external iliacs in the ventral abdominal walls. The superficial epigastrics and other secondary longitudinal vessels are formed in a similar manner.
The Development of the Arteries of the Limbs.  -  The earliest stages in the development of the limb arteries are unknown in man,
Fig. 154,
-Embryo of 13 mm. showing the Mode of Development of the Internal Mammary and Deep Epigastric Arteries.  -  (Mall.)
but it has been found that in the mouse the primary supply of the anterior limb bud is from five branches arising from the sides of the aorta. These anastomose to form a plexus from which later a single stem, the subclavian artery, is elaborated, occupying the position of the seventh cervical segmental vessel, the remaining branches of the plexus having disappeared. The common iliac artery similarly
represents the fifth lumbar segmental artery, but whether or not it also is elaborated from a plexus is as yet unknown.
The later history of the limb arteries is also but imperfectly known and one must rely largely upon the facts of comparative anatomy and on the anomalies that occur in the adult for indications of what the development is likely to be. The comparative evidence indicates the existence of several stages in the development of the limb vessels, and so far as embryological observations go they confirm the conclusions drawn from this source, although the various stages show apparently a great amount of overlapping owing to a concentration of the developmental stages. In the simplest arrangement the subclavian is continued as a single trunk along the axis of the limb as far as the carpus, where it divides into digital branches for the fingers. In its course through the forearm it lies in the interval between the radius and ulna, resting on the interosseous membrane, and in this part of its course it may be termed the arteria interossea. In the second stage a new artery accompanying the median nerve appears, arising from the main stem or brachial artery a little below the elbow-joint. This may be termed the arteria mediana, and as it develops the arteria interossea gradually diminishes in size, becoming finally the small volar interosseous artery of the adult (Fig. 155), and the median, uniting with its lower end, takes from it the digital branches and becomes the principal stem of the forearm.
A third stage is then ushered in by the appearance of a branch from the brachial which forms the arteria ulnaris, and this, passing down the ulnar side of the forearm, unites at the wrist with the median to form a superficial palmar arch from which the digital branches arise. A fourth stage is marked by the diminution of the median artery until it finally appears to be ,a small branch of the interosseous, and at the same time there develops from the brachial, at about the middle of the upper arm, what is known as the arteria radialis superficial (Fig. 155, rs). This extends down the radial side of the forearm, following the course of the radial nerve, and at the wrist passes upon the dorsal surface of the hand to form the
dorsal digital arteries of the thumb and index finger. At first this artery takes no part in the formation of the palmar arches, but later it gives rise to the superficial volar branch, which usually unites with the superficial arch, while from its dorsal portion a perforating branch develops which passes between the first and second meta
Fig. 155.  -  Diagrams showing an Early and a Late Stage in the Development
of the Arteries of the Arm.
b, Brachial; i, interosseous; m, median; r, radial; rs, superficial radial; u, ulnar.
carpal bones and unites with a deep branch of the ulnar to form the deep arch. The fifth or adult stage is reached by the development from the brachial below the elbow of a branch (Fig. 155, r) which passes downward and outward to unite with the superficial radial, whereupon the upper portion of that artery degenerates until it is
represented only by a branch to the biceps muscle (Schwalbe), while the lower portion persists as the adult radial.
The various anomalies seen in the arteries of the forearm are, as a rule, due to the more or less complete persistence of one or other of the stages described above, what is described, for instance, as the high branching of the brachial being the persistence of the superficial radial.
In the leg there is a noticeable difference in the arrangement of the arteries from what occurs in the arm, in that the principal artery of the thigh, the femoral, does not accompany the principal nerve, the sciatic. This difference is apparently secondary, but, as in the case of the upper limb, it is necessary to rely largely on the facts of comparative anatomy and on anomalies which occur in the human body for an idea of the probable development of the arteries of the lower limb. It has already been seen that the common iliac artery is to be regarded as a lateral branch of the dorsal aorta, and in the simplest condition of the limb arteries its continuation, the anterior division of the hypogastric, passes down the leg as a well-developed sciatic artery as far as the ankle (Fig. 156,5). At the knee it occupies the position of the popliteal of adult anatomy, and below the knee gives off a branch corresponding to the anterior tibial (at) which, passing forward to the extensor surface of the leg, quickly loses itself in the extensor muscles. The main artery continues downward on the interosseous membrane, and some distance above the ankle divides into a strong anterior and a weaker posterior branch; the former perforates the membrane and is continued down the extensor surface of the leg to form the lower part of the anterior tibial and the dorsalis pedis arteries, while the latter, passing upon the plantar surface of the foot, is lost in the plantar muscles. At this stage the external iliac is a secondary branch of the common iliac, being but poorly developed and not extending as far as the knee.
In the second stage the external iliac artery increases in size until it equals the sciatic, and it now penetrates the adductor magnus muscle and unites with the popliteal portion of the sciatic. Before doing this, however, it gives off a strong branch (sa) which accompanies the long saphenous nerve down the inner side of the leg, and,
passing behind the internal malleolus, extends upon the plantar surface of the foot, where it gives rise to the digital branches. From this arrangement the adult condition may be derived by the continued increase in size of the external iliac and its continuation, the femoral (/), accompanied by a reduction of the upper portion of the sciatic and its separation from its popliteal portion (p) to form the inferior gluteal artery of the adult. The continuation of the popli
i ,°
Fig. 156.  -  Diagrams Illustrating Stages in the Development of the Arteries
of the Leg.
at, Anterior tibial; dp, dorsalis pedis;/, femoral; p, popliteal; pe, peroneal pt, posterior
tibial; s, sciatic (inferior gluteal); sa, saphenous.
teal down the leg is the peroneal artery (pe) and the upper perforating branch of this unites with the lower one to form a continuous anterior tibial, the lower connection of which with the peroneal persists in part as the anterior peroneal artery. A new branch arises from the upper part of the peroneal and passes down the back of the leg
to unite with the lower part of the arteria saphena, forming the posterior tibial artery (pt), and the upper part of the saphenous becomes much reduced, persisting as the superficial branch of the art. genu suprema and a rudimentary chain of anastomoses which accompany the long saphenous nerve.
The Development of the Venous System.  -  The earliest veins to develop are those which accompany the first-formed arteries, the umbilicals, but it will be more convenient to consider first the veins which carry the blood from the body of the embryo back to the heart. These make their appearance, while the heart is still in the pharyngeal region, as two pairs of longitudinal trunks, the anterior and posterior cardinal veins, into which lateral branches, arranged more or less segmentally, open. The anterior cardinals appear somewhat earlier than the posterior and form the internal jugular veins of adult anatomy. Each vein extends forward from the heart at the side of the notochord and is continued on the under surface of the brain, lying medial to the roots of the cranial nerves. Later sprouts arising from the vein form loops around the nerve roots and the portion of the loops formed by the original vein then disappear, so that the vessel now lies lateral to the nerve roots, except in the case of the trigeminus, where the original vessel persists to form the cavernous sinus. From the vena capitis lateralis so formed three veins, an anterior, a middle and a posterior cerebral, pass to the brain, the anterior cerebral together with the ophthalmic vein opening into the anterior end of the cavernous sinus, the middle cerebral into the posterior extremity of the same sinus and the posterior cerebral into the vena capitis lateralis behind the ear vesicle (Fig. 157). The branches of the anterior cerebral vein extending over the cerebral hemisphere unite with their fellows of the opposite side to form a longitudinal trunk, the superior sagittal sinus, lying between the two cerebral hemispheres. At first this sinus drains by way of the anterior cerebral vein (Fig. 158, A), but as the cerebral hemispheres increase in size it is gradually carried backward and makes connections first with the middle cerebral and later with the posterior cerebral vein (Fig. 158, B and C), each of these becoming in turn the principal
drainage of the sinus. The connections which join the veins to the sinus become the proximal portion of the transverse sinus, the posterior cerebral vein itself becoming the distal portion, the middle cerebral vein becomes the superior petrosal sinus, while the anterior cerebral vein persists as the middle cerebral vein of adult anatomy
m vc i vcv
Fig. 157.  -  Reconstruction of the Head of a Human Embryo of 9 mm. showing
the Cerebral Veins. acv, Anterior cerebral vein; au, auditory vesicle; cs, cavernous sinus; fa, facial nerve; mcv, middle cerebral vein; pcv, posterior cerebral vein; tr, trigeminal nerve; vcl, lateral cerebral vein.  -  (Mall.)
(Fig. 158, C). Additional sprouts from the terminal portion of the superior sagittal sinus give rise to the straight and inferior sagittal sinuses, and, after the disappearacne of the vena capitis lateralis, a new stem develops between the cavernous and transverse sinuses, passing medial to the ear vesicle, and forms the inferior petrosal sinus (Fig. 158, C). This joins the transverse sinus at the jugular
foramen and from this junction onward the anterior cardinal vein may now be termed the internal jugular vein.
Passing backward from the jugular foramen the internal jugular veins unite with the posterior cardinals to form on each side a common trunk, the ductus Cuvieri, and then passing transversely toward the median line open into the sides of the sinus venosus. So long as the heart retains its original position in the pharyngeal region the jugular
Fig. 158.  -  Diagrams showing the Arrangement of the Cerebral Veins in Embryos of (A) the Fifth Week, (B) the Beginning of the Third Month and in (C) an Older Fetus.
acv, Anterior cerebral vein; cs, cavernous sinus; Us, inferior sagittal sinus; Inf. Pet., inferior petrosal sinus; Is, transverse sinus; ov, ophthalmic vein; sis, superior sagittal sinus; sps, spheno-parietal sinus; sr, straight sinus; 55, middle cerebral vein (Sylvian); sup. pet, superior petrosal sinus; th, torcular Herophili; v, trigeminal nerve; vca, anterior cerebral vein; vol. lateral cerebral vein; vcm, middle cerebral vein; vcp, posterior cerebral vein; vg, vein of Galen; vj, internal jugular.  -  (Mall.)
is a short trunk receiving lateral veins only from the uppermost segments of the neck and from the occipital segments, the remaining segmental veins opening into the inferior cardinals. As the heart recedes, however, the jugulars become more and more elongated
2 5 8
and the cervical lateral veins shift their communication from the cardinals to the jugulars, until, when the subclavians have thus shifted, the jugulars become much larger than the cardinals. When the sinus venosus is absorbed into the wall of the right auricle, the course of the left Cuvierian duct becomes a little longer than that of the right, and from the left jugular, at the point where it is joined by the left subclavian, a branch arises which extends obliquely across to join the right jugular, forming the left innominate vein. When this is established, the connection between the left jugular and Cuvierian duct is dissolved, the blood from the left side of the head and neck and from the left subclavian vein passing over to empty
Fig. 159.  -  Diagrams showing the Development of the Superior Vena Cava. a, Azygos vein; cs, coronary sinus; ej, external jugular; h, hepatic vein; ij, internal jugular; inr and inl, right and left innominate veins; s, subclavian; vci and vcs, inferior and superior venae cava?.
into the right jugular, whose lower end, togethei with the right Cuvierian duct, thus becomes the superior vena cava. The left Cuvierian duct persists, forming with the left horn of the sinus venosus the coronary sinus (Fig. 159).
The external jugular vein develops somewhat later than the internal. The facial vein, which primarily forms the principal affluent of this stem, passes at first into the skull along with the fifth nerve and communicates with the internal jugular system, but later
this original communication is broken and the facial vein, uniting with other superficial veins, passes over the jaw and extends down the neck as the external jugular. Later still the facial anastomoses with the ophthalmic at the inner angle of the eye and also makes connections with the internal jugular just after it has crossed the jaw, and so the adult condition is acquired.
It is interesting to note that in many of the lower mammals the external jugular becomes of much greater importance than the internal, the latter in some forms, indeed, eventually disappearing and the blood from the interior of the skull emptying by means of anastomoses which have developed into the external jugular system. In man the primitive condition is retained, but indications of a transference of the intracranial blood to the external jugular are seen in the emissary veins.
The posterior cardinal veins, or, as they may more simply be termed, the cardinals, extend backward from their union with the jugulars along the sides of the vertebral column, receiving veins from the mesentery and also from the various lateral segmental veins of the neck and trunk regions, with the exception of that of the first cervical segment which opens into the jugular. Later, however, as already described (p. 258), the cervical veins shift to the jugulars, as do also the first and second thoracic (intercostal) veins, but the remaining intercostals, together with the lumbars and sacrals, continue to open into the cardinals. In addition, the cardinals receive in early stages the veins from the primitive kidneys (meson ephros), which are exceptionally large in the human embryo, but when they are replaced later on by the permanent kidneys (metanephros) their afferent veins undergo a reduction in number and size, and this, together with the shifting of the upper lateral veins, produces a marked diminution in the size of the cardinals. The changes by which they acquire their final arrangement are, however, so intimately associated with the development of the inferior vena cava that their description may be conveniently postponed until the history of the vitelline and umbilical veins has been presented.
The vitelline veins are two in number, a right and a left, and pass in along the yolk-stalk until they reach the embryonic intestine, along the sides of which they pass forward to unite with the corre
sponding umbilical veins. These are represented in the bellystalk by a single venous trunk which, when it reaches the body of the embryo, divides into two stems which pass forward, one on each side of the umbilicus, and thence on each side of the median line of the ventral abdominal wall, to form with the corresponding vitelline veins common trunks which open into the ductus Cuvieri. As the liver develops it comes into intimate relation with the vitelline veins, which receive numerous branches from its substance and, indeed, seem to break up into a network (Fig. 160, A) traversing the liver
Vamd. Vb.7ns.
-Diagrams Illustrating the Transformations of the Vitelline and Umbilical Veins.
D.C, Ductus Cuvieri; D.V.A, ductus venosus; V.o.m.d and V.o.m.s, right and left vitelline veins; V.u.d and V.u.s, right and left umbilical veins.  -  (Hochstetter.)
substance and uniting again to form two stems which represent the original continuations of the vitellines. From the point where the common trunk formed by the right vitelline and umbilical veins opens into the Cuvierian duct a new vein develops, passing downward and to the left to unite with the left vitelline; this is the ductus venosus (Fig. 160, B, D.V.A). In the meantime three cross-connections have developed between the two vitelline veins, two of which pass ventral and the other dorsal to the intestine, so that the latter is
surrounded by two venous loops (Fig. 161, A), and a connection is developed between each umbilical vein and the corresponding vitelline (Fig. 160, B), that of the left side being the larger and uniting with the vitelline just where it is joined by the ductus venosus so as to seem to be the continuation of this vessel (Fig. 160, C). When these connections are complete, the upper portions of the umbilical veins degenerate (Fig. 161), and now the right side of the lower of the two vitelline loops which surround the intestine disappears, as does also that portion of the left side of the upper loop which intervenes
Fig. 161.  -  A, The Venous Trunks of an Embryo of 5 mm. seen from the Ventral Surface; B, Diagram Illustrating the Transformation to the Adult Condition.
Vcd and Vcs, Right and left superior venae cavae; Vj, jugular vein; V.om, vitelline vein; Vp, vena porta; Vu, umbilical vein (lower part); Vu', umbilical vein (upper part); Vud and Vus, right and left umbilical veins (lower parts).  -  (His.)
between the middle cross-connection and the ductus venosus, and so there is formed from the vitelline veins the vena porta.
While these changes have been progressing the right umbilical vein, originally the larger of the two (Fig. 160, A and B, V.u.d), has become very much reduced in size and, losing its connection with the left vein at the umbilicus, forms a vein of the ventral abdominal wall in which the blood now flows from above downward. The
left umbilical now forms the only route for the return of blood from the placenta, and appears to be the direct continuation of the ductus venosus (Fig. 161, C), into which open the hepatic veins, returning the blood distributed by the portal vein to the substance of the liver. Returning now to the posterior cardinal veins, it has been found that in the rabbit the branches which come to them from the mesentery anastomose longitudinally to form a vessel lying parallel and slightly ventral to each cardinal. These may be termed the sub
A £
Fig. 162.  -  Diagrams Illustrating the Development or the Inferior Vena Cava. The cardinal veins and ductus venosus are black, the subcardinal system blue, and the supracardinal yellow, cs, coronary sinus; dv, ductus venosus; il, iliac vein; r, renal; s, internal spermatic; scl, subclavian; sr, suprarenal; va, azygos; vha, hemiazygos; vi, innominate; vj, internal jugular.
cardinal veins (Lewis), and in their earliest condition they open at either end into the corresponding cardinal, with which they are also united by numerous cross-branches. Later, in rabbits of 8.8 mm., these cross-branches begin to disappear and give place to a large cross-branch situated immediately below the origin of the superior
mesenteric artery, and at the same point a cross-branch between the two subcardinals also develops. The portion of the right subcardial which is anterior to the cross-connection now rapidly enlarges and unites with the ductus venosus about where the hepatic veins open into that vessel (Fig. 162, A), and the portion of each posterior cardinal immediately above the entrance of the renal veins degenerates, so that all the blood received by the posterior portions of the cardinals is returned to the heart by way of the right subcardinal, its cross-connections, and the upper part of the ductus venosus.
When this is accomplished the lower portions of the subcardinals disappear, while the portions above the large cross-connection persist, greatly diminished in size, as the suprarenal veins (Fig. 162, B).
In the early stages the veins which drain the posterior abdominal walls empty into the posterior cardinals, and later they form, in the region of the kidney on each side, a longitudinal anastomosis which opens at either extremity into the posterior cardinal. The ureter thus becomes surrounded by a venous ring, the dorsal limb of which is formed by the new longitudinal anastomosis, which has been termed the supracardinal vein (McClure and Huntington), while the ventral limb is formed by a portion of the posterior cardinal (Fig. 162, B). Still later the ventral limb of the loop disappears and the dorsal supracardinal limb replaces a portion of the more primitive posterior cardinal. An anastomosis now develops between the right and left cardinals at the point where the iliac veins open into them (Fig. 162, B), and the portion of the left cardinal which intervenes between this anastomosis and the entrance of the internal spermatic vein disappears, the remainder of it, as far forward as the renal vein, persisting as the upper part of the left internal spermatic vein, which thus comes to open into the renal vein instead of into the vena cava as does the corresponding vein of the right side of the body (Fig. 162, C, s). The renal veins originally open into the cardinals at the point where these are joined by the large crossconnection, and when the lower part of the left cardinal disappears, this cross-connection forms the proximal part of the left renal vein, which consequently receives the left suprarenal (Fig. 162, C).
The observations upon which the above description is based have been made upon the rabbit, but it seems probable from the partial observations that have been made that similar changes occur also in the human embryo. It will be noted from what has been said that the inferior vena cava is a composite vessel, consisting of at least four elements: (1) the proximal part of the ductus venosus; (2) the anterior part of the right subcardinal; (3) the right supracardinal; and (4) the posterior part of the right cardinal.
The complicated development of the inferior vena cava naturally gives rise to numerous anomalies of the vein due to inhibitions of its development. These anomalies affect especially the post-renal portion, a persistence of both cardinals (interpreting the conditions in the terms of what occurs in the rabbit) giving rise to a double post-renal cava, or a persistence of the left cardinal and the disappearance of the right to a vena cava situated on the left side of the vertebral column and crossing to the right by way of the left renal vein. So, too, the occurrence of accessory renal veins passing dorsal to the ureter is explicable on the supposition that they represent portions of the supracardinal system of veins.
It has already been noted that the portions of the posterior cardinals immediately anterior to the entrance of the renal veins disappear. The upper part of the right vein persists, however, and becomes the vena azygos of the adult, while the upper portion of the left vein sends a cross-branch over to unite with the azygos and then separates from the coronary sinus to form the vena hemiazygos. At least this is what is described as occurring in the rabbit. In the cat, however, only the very uppermost portion of the right posterior cardinal persists and the greater portion of the azygos and perhaps the entire hemiazygos vein is formed from the prerenal portions of the supracardinal veins, the right one joining on to the small persisting upper portion of the right posterior cardinal, while the crossconnection between the hemiazygos and azygos represents one of the originally numerous cross-connections between the supracardinals.
The ascending lumbar veins, frequently described as the commencements of the azygos veins, are in reality secondary formations developed by the anastomoses of anteriorly and posteriorly directed branches of the lumbar veins,
The Development of the veins of the Limbs.  -  The development of the limb veins of the human embryo requires further investigation, but from a comparison of what is known with what has been observed in rabbit embryos it may be presumed that the changes which take place are somewhat as follows : In the anterior extremity the blood brought to the limb is collected by a vein which passes distally along the radial border of the limb bud, around its distal border, and proximally along its ulnar border to open into the anterior cardinal vein; this is the primary ulnar vein. Later a second vein grows out from the external jugular along the radial border of the limb, representing the cephalic vein of the adult, and on its appearance the digital veins, which were formed from the primary ulnar vein, become connected with it, and the distal portion of the primary ulnar vein disappears. Its proximal portion persists, however, to form the basilic vein, from which the brachial vein and its continuation, the ulnar vein, are developed, while the radial vein develops as an outgrowth from the cephalic, which at an early stage secures an opening into the axillary vein, its original communication with the external jugular forming the jugulo-cephalic vein.
In the lower limb a primary fibular vein, exactly comparable to the primary ulnar of the arm, surrounds the distal border of the limbbud and passes up its fibular border to open with the posterior cardinal vein. The further development in the lower limb differs considerably, however, from that of the upper limb. From the primary fibular vein an anterior tibial vein grows out, which receives the digital branches from the toes, and from the posterior cardinal, anterior to the point where the primary fibular opens into it, a vein grows down the tibial side of the leg, forming the long saphenous vein. From this the femoralvein is formed and from it the posterior tibial vein is continued down the leg. An anastomosis is formed between the femoral and the primary fibular veins at the level of the knee and the proximal portion of the latter vein then becomes greatly reduced, while its distal portion possibly persists as the small saphenous vein (Hochstetter).
The Pulmonary Veins.  -  The development of the pulmonary veins
has already been described in connection with the development of the heart (see p. 234).
The Fetal Circulation.  -  During fetal life while the placenta is the sole organ in which occur the changes in the blood on which the
Fig. 163.  -  The Fetal Circulation. ao, Aorta; a.pu., pulmonary artery; au, umbilical artery; da, ductus arteriosus; dv, ductus venosus; int, intestine; vci and vcs, inferior and superior vena cava; vh, hepatic vein; vp, vena portas; v.pu, pulmonary vein; vu, umbilical vein.  -  (From Kollmann.)
nutrition of the embryo depends, the course of the blood is necessarily somewhat different from what obtains in the child after birth. Taking the placenta as the starting-point, the blood passes along the
umbilical vein to enter the body of the fetus at the umbilicus, whence it passes forward in the free edge of the ventral mesentery (see p. 321) until it reaches the liver. Here, owing to the anastomoses between the umbilical and vitelline veins, a portion of the blood traverses the substance of the liver to open by the hepatic veins into the inferior vena cava, while the remainder passes on through the ductus venosus to the cava, the united streams opening into the right atrium. This blood, whose purity is only slightly reduced by mixture with the blood returning from the inferior vena cava, is prevented from passing into the right ventricle by the Eustachian valve, which directs it to the foramen ovale, and through this it passes into the left atrium, thence to the left ventricle, and so out by the systemic aorta.
The blood which has been sent to the head, neck, and upper extremities is returned by the superior vena cava also into the right atrium, but this descending stream opens into the atrium to the right of the annulus of Vieussens (see Fig. 141) and passes directly to the right ventricle without mingling to any great extent with the blood returning by way of the inferior cava. From the right ventricle this blood passes out by the pulmonary artery; but the lungs at this period are collapsed and in no condition to receive any great amount of blood, and so the stream passes by way of the ductus arteriosus into the systemic aorta, meeting there the placental blood just below the point where the left subclavian artery is given off. From this point onward the aorta contains only mixed blood, and this is distributed to the walls of the thorax and abdomen and to the lungs and abdominal viscera, the greater part of it, however, passing off in the hypogastric arteries and so out again to the placenta.
This is the generally accepted account of the fetal circulation and it is based upon the idea that the foramen ovale is practically a connection between the inferior vena cava and the left atrium. If it be correct the right ventricle receives only the blood returning to the heart by the vena cava superior, while the left receives all that returns by the inferior vena cava together with what returns by the pulmonary veins. One would, therefore, expect that the capacity and pressure of the right ventricle would in the fetus be less than those of the left. Pohlman, who has recently investigated the question in embryo pigs, finds, on the contrary, that the capacities and pressures of the two ventricles are equal and
maintains that the foramen ovale is actually a connection between the two atria. That is to say, he holds that there is an actual mingling of the blood from the two venae cava? in the right atrium, whence the mixed blood passes to the right ventricle, a certain amount of it, however, passing through the foramen ovale and so to the left ventricle to equalize the deficiency that would otherwise exist in that chamber owing to the small amount of blood returning by the pulmonary veins. According to this view there would be no difference in the quality of the blood distributed to different portions of the body, such as is provided for by the current theory; all the blood leaving the heart would be mixed blood and in favor of this view is the fact that starch granules injected into either the superior or the inferior vena cava in living pig embryos were in all cases recovered from both sides of the heart.
At birth the lungs at once assume their functions, and on the cutting of the umbilical cord all communication with the placenta ceases. Shortly after birth the foramen ovale closes more or less perfectly, and the ductus arteriosus diminishes in size as the pulmonary arteries increase and becomes eventually converted into a fibrous cord. The hypogastric arteries diminish greatly, and after they have passed the bladder are also reduced to fibrous cords, a fate likewise shared by the umbilical vein, which becomes converted into the round ligament of the liver.
The Development of the Lymphatic System.  -  Concerning the development of the lymphatic system two discordant views exist, one (Sabin, Lewis) regarding it in its entirety as a direct development from the venous system, while the other (Huntington, McClure) recognizes for it a dual origin, a portion being derived directly from the venous system and the rest from a series of mesenchymal spaces developing in relation to veins but quite unconnected with them.
The portion of the system concerning which harmony prevails is that which forms the connection with the venous system in the adult and constitutes what in the embryo is termed the jugular lymph sac. In the early stages of development a capillary network extends along the line of the jugular veins, communicating with them at various points. In embryos of 10 mm. a portion of this network, on either side of the body, becomes completely separated
from the jugular and gives rise to a number of closed cavities lined with endothelium and situated in the neighborhood of the junction of the primary ulnar and cephalic veins with the jugular. In
Fig. 164.  -  Diagrams showing the Arrangement of the Lymphatic Vessels in Pig Embryos of (4) 20 mm. and (B) 40 mm. ACV, Jugular vein; ADR, suprarenal body; ALU, jugular lymph sac; Ao, aorta Arm D, deep lymphatics to the arm; D, diaphragm; Du, branches to duodenum FV, femoral vein; H, branches to heart; K, kidney; LegD, deep lymphatics to leg Lu, branches to lung; MP, branches to mesenteric plexus; CE, branch to oesophagus PCV, cardinal vein: PLH, posterior lymph sac; RC, cisterna chyli; RLD, right lymphatic duct; ScV, subclavian vein; SV, sciatic vein; St, branches to stomach; TD, thoracic duct; WB. Wolffian body.  -  (Sdbin.)
later stages these cavities enlarge and unite to form a large sac, the jugular lymph sac (Fig. 164, ALU), and this, still later, makes a
new connection with the jugular, the opening being guarded by a valve. This communication becomes the adult communication of the thoracic duct or right lymphatic duct with the venous system, but the sac itself, as development proceeds, becomes divided into smaller portions and gives rise to a number of lymph nodes.
A similar pair of lymph sacs also develop in relation to the sciatic vein, but their exact mode of origin is uncertain. In embryos of 20 mm. venous plexuses, similar to the jugular plexuses of younger stages, are found accompanying the sciatic veins, and a little later there are found in the same region a pair of posterior or sciatic lymph sacs (Fig. 164, PLH), which, like the jugular sacs, later give rise to a series of lymph nodes. At about the same stage of development & retroperitoneal sac (Fig. 165, Lsr) is also formed in the root of the mesentery cranial to the origin of the superior mesenteric artery, and this, too, later gives rise to a plexus of lymphatic vessels in connection with which the mesenteric lymphatic nodes develop. This last sac is much more pronounced in the pig embryo than in man, and in that form it has been found to have its origin from a capillary network that separates from the renal veins (Baetjer).
There are thus formed five sacs, all of which are associated with the formation of groups of lymphatic nodes, and in the case of one pair at least it is agreed that they are directly developed from venous capillaries. It is in connection with the remaining sac and especially with the formation of the thoracic duct and the peripheral lymphatics that the want of harmony referred to above occurs. The first portion of the thoracic duct to appear is the cisterna chyli, which is found in embryos of 23 mm. in the region of the third and fourth lumbar segments, in close proximity to the vena cava (Fig. 165, Cc). After its appearance the rest of the thoracic duct develops quickly, it being completely formed in embryos of 30 mm., and it is interesting to note that at this stage the duct is paired in its caudal portion, two trunks passing forward from the cisterna chyli, the right one passing behind the aorta and uniting with the left after it has entered the thorax.
The mode of origin of the duct has not yet been made out in human embryos. In the pig and rabbit isolated spaces lined with endothelium occur along the course of the duct, but without communicating with it, and the fact that some of these showed connection with the neighboring azygos veins gave basis for the view that they were the remains of a venous capillary plexus from which the duct had developed. It is possible, however, that the duct is formed
T Fig. 165.  -  Diagram of the Posterior Portion of the Body of a Human Embryo of 23 mm., showing the Relations of the Retroperitoneal Lymph Sac and the Cisterna Chyli to the Veins.
Am, Superior mesenteric artery; Ao, aorta; Cc, cisterna chyli; Isr, retroperitoneal lymph sac; S, suprarenal body; Va, vena azygos; Vci, vena cava inferior; vl u first lumbar vertebra; vs u first sacral vertebra.  -  (After Sabin.)
by the union of outgrowths from the cisterna chyli and jugular sac, in which case it would also be a derivative of the venous system, provided that the cisterna chyli is formed in the same way as the jugular sac. Huntington and McClure, however, maintain that it
is formed by the fusion of spaces appearing in the mesenchyme immediately external to the intima of degenerating veins; hence the spaces are termed extraintimal spaces. These at first have no endothelial lining and they are never in connection with the lumina of the veins. They are perfectly independent structures and any connections they may«nake with the venous system are entirely secondary. This mode of origin from extraintimal spaces is not
confined to the thoracic duct, according to the authors mentioned, but is the method of development of all parts of the lymphatic system, with the exception of the jugular sacs. According to the supporters of the direct venous origin the peripheral lymphatic stems develop, like blood-vessels, as outgrowths from the stems already present.
Lymph nodes nave not been observed in human embryos until toward the end of the third month of development, but ' ! .<l'-V''\LY. they appear in pig embryos of 3 cm. X^Hi^. Their unit of structure is a blood-vessel, breaking up at its termination into a leash of capillaries, around which a condensation of lymphocytes occurs in the mesenchyme. A structure of this kind forms what is termed a lymphoid follicle and may exist, even in this simple condition, in the adult. More frequently, however, there are associated with the follicle lymphatic vessels, or rather the follicle develops in a network of lymphatic vessels, which, become an investment of the follicle and form with it a simple lymph node (Fig. 166). This condition is, however, in many cases but transitory, the artery branching and collections of lymphoid tissue forming around each of the branches, so that a series of follicles are formed, which, together with the surrounding lymphatic vessels, become enclosed by a connective-tissue capsule to
Fig. 166. -  Diagram of a Primary Lymph Node of an Embryo Pig of 8 cm. a, Artery; aid, afferent lymph duct; eld, efferent lymph duct; /, follicle.  -  (Sabin.)
form a compound lymph node. Later trabecular of connective tissue extend from the capsule toward the center of the node, between the follicles, the lymphatic network gives rise to peripheral and central lymph sinuses, and the follicles, each with its arterial branch, constitute the peripheral nodules and the medullary cords, the portions of these immediately surrounding the leash of capillaries into which
tt- be
Fig. 167.  -  Developing H^emolymph Node.
be, central blood-vessel; bh, blood-vessel at hilus; ps, peripheral blood sinus.  -  (Sabin
from Morris' Human Anatomy.)
the artery dissolves, constituting the so-called germ centers in which multiplication of the lymphocytes occurs.
In various portions of the body, but especially along the root of
the mesentery, what are termed hcemolymph nodes occur. In these
the lymph sinus is replaced by a blood sinus, but with this exception
their structure resembles that of an ordinary lymph node, a simple
one consisting of a follicle, composed of adenoid tissue with a central blood-vessel, and a peripheral blood sinus (Fig. 167).
The Development of the Spleen.  -  Recent studies (Mall) have shown that the spleen may well be regarded as possessing a structure comparable to that of the lymph nodes, the pulp being more or less distinctly divided by trabecular into areas termed pulp cords, the axis of each of which is occupied by a twig of the splenic artery. The spleen, therefore, seems to fall into the same category of organs as the lymph and hsemolymph nodes, differing from these chiefly in the absence of sinuses. It has generally been regarded as a development of the mesenchyme situated between the two layers of the mesogastrium. To this view, however, recent observers have taken exception, holding that the ultimate origin of the organ is in part or entirely from the ccelomic epithelium of the left layer of the mesogastrium. The first indication of the spleen has been observed in embryos of the fifth week as a slight elevation on the left (dorsal) surface of the mesogastrium, due to a local thickening and vascularization of the mesenchyme, accompanied by a thickening of the ccelomic epithelium which covers the elevation. The mesenchyme thickening presents no differences from the neighboring mesenchyme, but the epithelium is not distinctly separated from it over its entire surface, as it is elsewhere in the mesentery. In later stages, which have been observed in detail in pig and other amniote embryos, cells separate from the deeper layers of the epithelium (Fig. 168) and pass into the mesenchyme thickening, whose tissue soon assumes a different appearance from the surrounding mesenchyme by its cells being much crowded. This migration soon' Ceases, however, and in embryos of forty-two days the ccelomic epithelium covering the thickening is reduced to a simple layer of cells.
The later stages of development consist of an enlargement of the thickening and its gradual constriction from the surface of the mesogastrium, until it is finally united to it only by a narrow band through which the large splenic vessels gain access to the organ The cells differentiate themselves into trabecular and pulp cords
special collections of lymphoid cells around the branches of the splenic artery forming the Malpighian corpuscles.
It has already been pointed out (p. 225) that during embryonic life the spleen is an important haematopoietic organ, both red and white corpuscles undergoing active formation within its substance. The Malpighian corpuscles are collections of lymphocytes in which multiplication takes place, and while nothing is as yet known as to the fate of the cells which are contributed to the spleen from the ccelomic epithelium, since they quickly come to resemble the mesenchyme cells with which they are associated, yet the growing number of observations indicating an epithelial origin for lymphocytes suggests the possibility that the cells in question may be responsible for the first leukocytes of the spleen.
" ' . .
Fig. 168.  -  Section through the Left Layer of the Mesogastrium of a Chick
Embryo of Ninety-three Hours, Showing the Origin of the Spleen.
ep, Ccelomic epithelium; ms, mesenchyme.  -  (Tonkoff.)
The Coccygeal or Luschka's Ganglion.  -  In embryos of about 15 cm. there is to be found on the ventral surface of the apex of the coccyx a small oval group of polygonal cells, clearly separated from the surrounding tissue by a mesenchymal capsule. Later, connective-tissue trabecular make their way into the mass, which thus becomes divided into lobules, and, at the same time, a rich vascular supply, derived principally from branches of the middle sacral artery, penetrates the body, which thus assumes the adult condition in which it presents a general resemblance to a group of lymph follicles.
It has generally been supposed that the coccygeal ganglion was in part derived from the sympathetic nervous system and belonged to the same group of organs as the suprarenal bodies. The most recent
work on its development (Stoerk) tends, however, to disprove this view, and the ganglion seems accordingly to find its place among the lymphoid organs.
W. A. Baetjer: "On the Origin of the Mesenteric Sac and the Thoracic Duct in the
Embryo Pig," Amer. Journ. Anat., vin, 1908. E. van Beneden and C. Julln: "Recherches sur la formation des annexes fcetales
chez les mammiferes," Archives de Biolog., v, 1884. A. C. Bernays: " Entwickehingsgeschichte der Atrioventricularklappen," Morphol.
Jahrbuch, 11, 1876. G. Born: "Beitrage zur Entwicklungsgeschichte des Saugethierherzens," Archiv
fiir mikrosk. Anat., xxxiii, 1889. J. L. Bremer: " On the Origin of the Pulmonary Arteries in Mammals," Anat. Record,
in, 1909. I. Broman: "Ueber die Entwicklung, Wanderung und Variation der Bauchaorten
zweige bei den Wirbeltiere," Ergeb. Anat. und Entwick., xvi, 1906. I. Broman: " Ueber die Entwicklung und "Wanderung" der Zweige der aorta abdom
inalis beim Menschen," Anat. Hefte, XXXVI, 1908. E. E. Butterfield: "Ueber die ungranulierte Vorstufen der Myelocyten und ihre
Bildung in Milz, Leber und Lymphdriisen," Deutsch. Arch. f. klin. Med., xcn,
E. R. Clark: " Observations on Living Growing Lymphatics in the Tail of the Frog
Larva," Anat. Record, in, 1909.
C. B. Coulter: "The Early Development of the Aortic Arches of the Cat, with
Especial Reference to the Presence of a Fifth Arch." Anat. Record, III, 1909.
D . M. Davis: " Studies on the Chief Veins in Early Pig Embryos and the Origin of the
Vena Cava Inferior," Amer. Journ. Anat., x, 1910. J. Disse: "Die Entstehung des B lutes und der ersten Gefasse im Huhnerei," Archiv
fiir mikrosk. Anat., xvi, 1879. A. C. F. Eternod: "Premiers stades de la circulation sanguine dans l'ceuf et Pembryon
humain," Anat. Anzeiger, xv, 1899. H. M. Evans: "On the Development of the Aortae, Cardinal and Umbilical Veins,
and the other Blood-vessels of Vertebrate Embryos from Capillaries," Anat.
Record, in, 1909. V. Federow: "Ueber die Entwicklung der Lungenvene," Anat. Hefte, xl, 1910. W. Felix: " Zur Entwicklungsgeschichte der Rumpfarterien des menschlichen Embryo,"
Morphol. Jahrb., xli, 1910. G. J. Heuer: "The Development of the Lymphatics in the Small Intestine of the
Pig," Amer. Journ. Anat., ix, 1909. W. His: "Anatomie menschlicher Embryonen," Leipzig, 1880-1882.
F. Hochstetter: "Ueber die ursprungliche Hauptschlagader der hinteren Gliedmasse
des Menschen und der Saugethiere, nebst Bemerkungen iiber die Entwicklung der Endaste der Aorta abdominalis," Morphol. Jahrbuch, xvi, 1890.
F. Hochstetter: "Ueber die Entwicklung der A. vertebralis beim Kaninchen, nebst Bemerkungen uber die Entstehung der Ansa Vieusseni," Morphol. Jahrbuch, XVI, 1890.
F. Hochstetter: "Beitrage zur Entwicklungsgeschichte des Venensystems der
Amnioten." Morphol. Jahrbuch, xx, 1893. W. H. Howell: "The Life-history of the Formed Elements of the Blood, Especially
the Red Blood-corpuscles," Journ. of Morphol., iv, 1890. W. H. Howell: "Observations on the Occurrence, Structure, and Function of the
Giant-cells of the Marrow," Journ. of M or ph., rv, 1890.
G. S. Huntington: "The Genetic Principles of the Development of the Systemic
Lymphatic Vessels in the Mammalian Embryo," Anal. Record, iv, 1910. G. S. Huntington: "The Anatomy and Development of the Systemic Lymphatic
Vessels of the Domestic Cat," Memoirs of Wistar Institute, 1, 1912. G. S. Huntington and C. F. W. McClure: "Development of Post-cava and Tributaries in the Domestic Cat," Amer. Journ. Anat., vi, 1907. G. S. Huntington and C. F. W. McClure: "The Development of the Main Lymph
Channels of the Cat in their Relations to the Venous System," Amer. Journ
Anat., vi, 1907. G. S. Huntington and C. F. W. MtjClure: "The Anatomy and Development of
the Jugular Lymph Sacs in the Domestic Cat," Amer. Journ. Anat., x, 1910. H. E. Jordan: "A Microscopical Study of the Umbilical Vesical of a 13 mm. Human
Embryo, with Special Reference to the Entodermal Tubules and the Blood
Islands," Anat. Anzeiger, xxxvn, 1910. C. A. Kling: "Studien uber die Entwicklung der Lymphdriisen beim Menschen,"
Archiv.fiir mikrosk. Anal., lxiii, 1904. H. Lehmann: " On the Embryonic History of the Aortic Arches in Mammals," Anat.
Anzeiger, xxvi, 1905. F. T. Lewis: "The Development of the Vena Cava Inferior," Amer. Journ. of Anat.,
1, 1902. F. T. Lewis: "The Development of the Veins in the Limbs of Rabbit Embryos."
Amer. Journ. Anat., v, 1906. F. T. Lewis: "The Development of the Lymphatic System in Rabbits," Amer. Journ.
Anat., v, 1906. F. T. Lewis: "On the Cervical Veins and Lymphatics in Four Human Embryos,"
Amer. Journ. Anat., ix, 1909. F. T. Lewis: "The First Lymph Glands in Rabbit and Human Embryos," Anat.
Record, in, 1909. W. A. Locy: "The Fifth and Sixth Aortic Arches in Chick Embryos, with Comments
on the Condition of the same Vessels in other Vertebrates," Anat. Anzeiger
xxix, 1906. F. P. Mall: "Development of the Internal Mammary and Deep Epigastric Arteries
in Man," Johns Hopkins Hospital Bulletin, 1898. F. P. Mall: "On the Developmennt of the Blood-vessels of the Brain in the Human
Embryo," Amer. Journ. Anat., iv, 1905. A. Maximow: " Untersuchungen liber Blut und Bindegewebe," Arch, fur mikr. Anat.,
Lxxni, 1909; lxxiv, 1909; lxxvi, 1910.
C. F. W. McClure: "The Development of the Thoracic and Right Lymphatic Ducts
in the Domestic Cat (Felis Domestica)," Anat. Anzeiger, xxxii, 1908. C. F. W. McClure: " The Extra-intimal Theory of the Development of the Mesenteric
Lymphatics in the Domestic Cat," Verhandl. Anat. Gesellsch., xxiv, 1910. C. S. Minot: "On a Hitherto Unrecognized Form of Blood Circulation without
Capillaries in the Organs of Vertebrata," Proc. Boston Soc. Nat. Hist., xxix, 1900. S. Molleer: "Die Blutbildung in der Embryonalen Leber des Menschen und der
Saugetiere," Arch.filr mikrosk. Anat., Lxxrv, 1909. A. G. Pohlman: "The Course of the Blood through the Fetal Mammalian Heart,"
Anat. Record, n, 1908. F. Reagan: "The Fifth Aortic Arch of Mammalian Embryos." Amer. Journ. Anat...
xii, 1912.
E. Retterer: "Sur la part que prend 1' epithelium a la formation de la bourse de
Fabricius, des amygdales et des plaques de Peyer," Journ. de I' Anat. et de la
Physiol., xxix, 1893. R. Retzer: "Some Results of Recent Investigations on the Mammalian Heart,"
Anat. Record, 11, 1908. C. Rose: "Zur Entwicklungsgeschichte des Saugethierherzens," Morphol. Jahrbuch,
xv, 1889. Florence R. Sabln: "On the Origin of the Lymphatic System from the Veins and
the Development of the Lymph Hearts and Thoracic Duct in the Pig," Amer.
Journ. of Anat., I, 1902. Florence R. Sabin: "The Development of the Lymphatic Nodes in the Pig and
their Relation to the Lymph Hearts," Amer. Journ. Anat., rv, 1905. Florence R. Sabin: "Further Evidence on the Origin of the Lymphatic Endothelium
from the Endothelium of the Blood Vascular System," Anat. Record, 11, 1908. Florence R. Sabin: On the Development of the Lymphatic System in Human > Embryos with a Consideration of the Morphology of the System as a Whole,"
Amer. Journ. Anat., ix, 1909. Florence R. Sabin: "A Critical Study of the Evidence Presented in Several Recent
Articles on the Development of the Lymphatic System," Anat. Record, v, 1911.
F. Saxer: "Ueber die Entwicklung und der Bau normaler Lymphdrusen und die
Entsehung der roten und weissen Blutkorperchen," Anat. Hefte, vi, 1896. H. Schridde: "Die Entstehung der ersten embryonalen Blutzellen des Menschen,"
Folia hcematol, rv, 1907. P. Stohr: "Ueber die Entwicklung der Darmlymphknotchen und iiber die Riick
bildung von Darmdrusen," Archiv fur mikrosk. Anat., LI, 1898. O. van der Stricht: " Nouvelles recherches sur la genese des globules rouges et des
globules blancs du sang," Archives de Biolog., xn, 1892. O. van der Stricht: "De la premiere origine du sang et des capillaires sanguins dans
l'aire vasculaire du Lapin," Comptes Rendus de la Soc. de Biolog. Paris, -Ser. 10,
11, 1895. O. Stoerk: "Ueber die Chromreaktion der Glandula coccygea und die Beziehung,
dieser Druse zum Nervus sympathicus," Arch, fur mikroskop. Anat., lxix, 1906. J. Tandler: "Zur Entwicklungsgeschichte der Kopfarterien bei den Mammalia."
Morphol. Jahrbuch, xxx, 1902.
J. Tandler: "Zur Entwickelungsgeschichte der menschlichen Darmarterien," Anat.
Hefte, xxiii, 1903. J. Tandler: " Ueber die Varietaten der arteria coeliaca und deren Entwicklung," Anat.
Hefte, xxv, 1904. J. Tandler: " Ueber die Entwicklung des fiinften Aortenbogens und der fiinften
Schlundtasche beim Menschen," Anat. Hefte, xxxvin, 1909. W. Tonkoff: " Die Entwickelung der Milz bei den Amnioten," Arch, fiir mikrosk.
Anat., lvi, 1900. Bertha de Vriese: "Recherches sur revolution des vaissaux sanguins des membres
chez l'homme," Archives de Biolog., xvili, 1902. F. Weidenreich: "Die roten Blutkorperchen," Ergeb. Anat. und Entwick., xiii, 1903
xiv, 1904. F. Weidenreich: "Die Leucocyten und verwandte zellformen," Ergeb. Anat. und;
Entwick., xvi, 191 1. J. H. Wright: "The Histogenesis of the Blood Platelets," Journ. of Morph., xxr, 1910.
The greatest portion of the digestive tract is formed by the constriction off of the dorsal portion of the yolk-sac, as shown in Fig. 52, the result being the formation of a cylinder, closed at either end, and composed of a layer of splanchnic mesoderm lined on its inner surface by endoderm. This cylinder is termed archenteron and has connected with it the yolk-stalk and the allantois, the latter communicating with its somewhat dilated terminal portion, which also receives the ducts of the primitive kidneys and is known as the cloaca (Fig. 170).
At a very early stage of development the anterior end of the embryo begins to project slightly in front of the yolk-sac, so that a shallow depression is formed between the two structures. As the constriction of the embryo from the sac proceeds, the anterior portion of the brain becomes bent ventrally and the heart makes its appearance immediately in front of the anterior surface of the yolk-sac, and so the depression mentioned above becomes deepened (Fig. 169) to form the oral sinus. The floor of this, lined by ectoderm, is immediately opposite the anterior end of the archenteron, and, since mesoderm does not develop in this region, the ectoderm of the sinus and the endoderm of the archenteron are directly in contact, forming a thin pharyngeal membrane separating the two cavities (Fig. 169, pm) In embryos of 2.15 mm. this membrane is still existent, but soon after it becomes perforated and finally disappears, so that the archenteron and oral sinus become continuous.
Toward its posterior end trr; archenteron comes into somewhat similar relations with the ectoderm, though a marked difference is noticeable in that the area over which the cloacal endoderm is in
contact with the ectoderm to form the cloacal membrane (Fig. 170, cm) lies a little in front of the actual end of the archenteric cylinder, the portion of the latter which lies posterior to the membrane forming what has been termed the postanal gut (p. an). This diminishes in size during development and early disappears altogether, and the pouch-like fold seen in Fig. 170 between the intestinal portion of the archenteron and the allantoic stalk (al) deepening until its floor comes into contact with the cloacal membrane, the cloaca becomes divided into a ventral portion, with which the allantois and the primitive excretory ducts (w) are connected, and a dorsal portion which becomes the lower end of the rectum. This latter abuts upon the dorsal portion of the cloacal membrane, and this eventually ruptures, so that the posterior communication of the archenteron with the exterior becomes established. This rupture, however, does not occur until a comparatively late period of development, until after the embryo has reached the fetal stage; nor does the position of the membrane correspond with the adult anus, since later there is a considerable development of mesoderm around the mouth of the cloaca, bulging out, as it were, the surrounding ectoderm, more especially anteriorly where it forms the large genital tubercle (see Chapter XIII), and posteriorly where it produces the anal tubercle. This appears as a rounded elevation on each side of the median line, immediately behind the cloacal membrane and separated from the root of the caudal projection by a depression, the precaudal recess. Later the two elevations unite across the median line to form a transverse ridge, the ends of which curve
Fig. 169.  -  Reconstruction of the Anterior Portion of an Embryo of 2.15
ab. Aortic bulb; h, heart; 0, auditory capsule; op, optic evagination;/>?w, pharyngeal membrane.  -  (His.)
forward and eventually meet in front of the original anal orifice. From the mesoderm of the circular elevation thus produced the external sphincter ani muscle is formed, and it would seem that so much of the lower end of the rectum as corresponds to this muscle is formed by the inner surface of the elevation and is therefore ectodermal. The definitive anus being at the end of this terminal portion of the gut is therefore some distance away from the position of the original cloacal membrane.
Fig. 170.  -  Reconstruction of the Hind End of an Embryo 6.5 mm. Long
al, Allantois; b, belly-stalk; cl, cloaca; cm, cloacal membrane; i, intestine; n, spinal cord; nc, notochord; p.an, postanal gut; ur, outgrowth to form ureter and metanephros; w, Wolffian duct.  -  (Keibel.)
It will be noticed that the digestive tract thus formed consists of three distinct portions, an anterior, short, ectodermal portion, an endodermal portion representing the original archenteron, and a posterior short portion which is also ectodermal. The differentiation of the tract into its various regions and the formation of the various organs found in relation with these may now be considered.
The Development of the Mouth Region.  -  The deepening of the oral sinus by the development of the first branchial arch and its separation into the oral and nasal cavities by the development of the palate have already been described (p. 99), but, for the sake of continuity in description, the latter process may be briefly recalled. At first the nasal pits communicate with the oral sinus by grooves lying one on each side of the fronto-nasal process, but by the union of the latter, through its processus globularis, with the maxillary processes these communications are interrupted and the floors of the nasal pits are separated from the oral cavity by thin bucco-nasal membranes, formed of the nasal epithelium in contact with that of the oral cavity. In embryos of about 15 mm. these membranes break through and disappear, and the nasal and oral cavities are again in communication, but the communications are now behind the maxillary processes and constitute what are termed the primitive choance. The oral cavity at this stage does not, however, correspond with the adult mouth cavity, since there is as yet no palate, the roof of the oral cavity being the base of the skull. From the maxillopalatine portions of the upper jaw, shelf-like ridges begin to grow, being at first directed downward so that their surfaces are parallel with the sides of the tongue, which projects up between them. Later, however, they become bent upward to a horizontal position (Fig. 171) and eventually meet in the median line to form the palate, separating the nasal cavities from the mouth cavity. All that portion of the original oral cavity which lies behind the posterior edge of the palatal shelf is now known as the pharynx, the boundary between this and the mouth cavity being emphasized by the prolongation backward and downward of the posterior angles of the palatal shelf as ridges, which form the pharyn go -palatine arches (posterior pillars of the fauces) . The nasal cavities now communicate with the upper part of the pharynx (naso-pharynx) by the posterior choanae. The palatal processes are entirely derived from the maxillary processes, the premaxillary portion of the upper jaw, which is a derivative of the fronto-nasal processes, not taking part in their formation/ Consequently a gap exists between the palatal
shelves and the premaxillae for a time, by which the nasal and mouth cavities communicate; it places the organ of Jacobson (see p. 429) in communication with the mouth cavity and may persist until after birth. Later it becomes closed over by mucous membrane, but may be recognized in the dried skull as the foramen incisivum (anterior palatine canal).
Occasionally there is a failure of the union of the palatal plates, the condition known as cleft palate resulting. The inhibition of development which brings about this condition may take place at different stages, but frequently it occurs while the plates still have an almost vertical direction. Typically cleft palate is a deficiency in the median line of the roof of the
Fig. 171.  -  View of the Roof of the Oral Fossa of Embryo showing the Lipgroove and the Formation of the Palate.  -  (His.)
mouth, not affecting the upper jaw, but very frequently it is combined with the defect which produces hare-lip (see p. 100), in which case the cleft may be continued through the upper jaw between its maxillary and premaxillary portions on either or both sides, according to the extent of the defect.
At about the fifth week of development a downgrowth of epithelium into the substance of both the maxillary and fronto-nasal processes above and the mandibular process below takes place, and the surface of the downgrowth becomes marked by a deepening groove (Fig. 171), which separates an anterior fold, the Up, from the jaw proper (Fig. 172). Mention should also be made of the
fact that at an early stage of development a pouch is formed in the median line of the roof of the oral sinus, just in front of the pharyngeal membrane, by an outgrowth of the epithelium. This pouch, known as Rathke's pouch, comes in contact above with a downgrowth from the floor of the brain and forms with it the pituitary body (seep. 399).
The Development of the Teeth.  -  When the epithelial downgrowth which gives rise to the lip groove is formed, a horizontal outgrowth develops from it which extends backward into the substance of the jaw, forming what is termed the dental shelf (Fig. 172, A). This at first is situated on the anterior surface of the jaw, but with the continued development of the lip fold it is gradually shifted until it comes to lie upon the free surface (Fig. 172, B), where its superficial edge is marked by a distinct groove, the dental groove (Fig. 171). At first the dental shelf of each jaw is a continuous plate of cells, uniform in thickness throughout its entire width, but later ten thickenings develop upon its deep edge, and beneath each of these the mesoderm condenses to form a dental papilla, over the surface of which the thickening moulds itself to form a cap, termed the enamel organ (Fig. 172, B). These ten papillae in each jaw, with their enamel caps, represent the teeth of the first dentition.
The papillae do not, however, project into the very edge of the dental shelf, but obliquely into what, in the lower jaw, was originally its under surface (Fig. 172, B), so that the edge of the shelf is free to grow still deeper into the surface of the jaw. This it does, and upon the extension so formed there is developed in each jaw a second set of thickenings, beneath each of which a dental papilla again appears. These tooth-germs represent the incisors, canines, and premolars of the permanent dentition. The lateral edges of the dental shelf being continued outward toward the articulations of the jaws as prolongations which are not connected with the surface epithelium, opportunity is afforded for the development of three additional thickenings on each side in each jaw, and, papillae developing beneath these, twelve additional tooth-germs are formed. These represent the permanent molars; their formation is much
later than that of the other teeth, the germ of the second molar not appearing until about the sixth week after birth, while that of the third is delayed until about the fifth year.
As the tooth-germs increase in size, they approach nearer and nearer to the surface of the jaw, and at the same time the enamel organs separate from the dental shelf until their connection with it is a mere neck of epithelial cells. In the meantime the dental shelf itself has been undergoing degeneration and is reduced to a reticulum
W'- : ^^^^^0^ :i '
Fig. 172.  -  Transverse Sections through the Lower Jaw showing the Formation of the Dental Shelf in Embryos of (A) 17 mm. and (B) 40 mm.  -  (Rose.)
which eventually completely disappears, though fragments of it may occasionally persist and give rise to various malformations. With the disappearance of the last remains of the shelf, the various toothgerms naturally lose all connection with one another.
It will be seen, from what has been said, that each tooth-germ consists of two portions, one of which, the enamel organ, is derived from the ectoderm, while the other, the dental papilla, is mesen
chymatous. Each of these gives rise to a definite portion of the fully formed tooth, the enamel organ, as its name indicates, producing the enamel, while from the dental papilla the dentine and pulp are formed.
The cells of the enamel organ which are in contact with the surface of the papilla, at an early stage assume a cylindrical form and become arranged in a definite layer, the enamel membrane (Fig. 173, SEi), while the remaining cells (SEa) apparently degenerate eventually, though they persist for a time to form what has been termed the enamel pulp. The formation of the enamel seems to be due to the direct transformation of the enamel cells, the process beginning at the basal portion of each cell, and as a result, the enamel consists of a series of prisms, each of which represents one of the cells of the enamel membrane. The transformation proceeds until the cells have become completely converted into enamel prisms, except at their very tips, which form a thin membrane, the enamel cuticle, which is shed soon after the eruption of the teeth.
The dental papillae are at first composed of a closely packed mass of mesenchyme cells, which later become differentiated into connective tissue into which blood-vessels and nerves penetrate. The superficial cells form a more or less definite layer (Fig. 173, od), and are termed odontoblasts, having the function of manufacturing the dentine. This they accomplish in the same manner as that in which the periosteal osteoblasts produce bone, depositing the dentine between their surfaces and the adjacent surface of the enamel. The outer surface of each odontoblast is drawn out into a number of exceedingly fine processes which extend into the dentine to occupy the minute dentinal tubules, just as processes of the osteoblasts occupy the canaliculi of bone.
At an early stage the enamel membrane forms an almost complete investment for the dental papilla (Fig. 173), but as the ossification of the tooth proceeds, it recedes from the lower part, until finally it is confined entirely to the crown. The dentine forming the roots of the tooth then becomes enclosed in a layer of cement, which is true bone and serves to unite the tooth firmly to the walls of its
socket. As the tooth increases in size, its extremity is brought nearer to the surface of the gum and eventually breaks through, the eruption of the first teeth usually taking place during the last half of the first year after birth. The growth of the permanent teeth