Book - Text-Book of the Embryology of Man and Mammals 9
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Hertwig O. Text-book of the embryology of man and mammals. (1892) Translated 1901 by Mark EL. from 3rd German Edition. S. Sonnenschein, London.
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Development of Connective Substance and Blood
(The Parablast- and Mesenchyme-Theories)
WITH the question of the origin of connective or mechanically sustentative substance and blood we enter a very difficult field, the cultivation of which has now been taken in hand successfully by many persons. Here also we shall acquaint ourselves with a simple case from the development of Invertebrates, before we begin with the conditions in Vertebrates, which are more difficult to comprehend.
In Ccelenterates and Echinoderms there is developed between the germ-layers, which are composed of epithelial cells, a sustentative tissue. It consists of a homogeneous jelly, in which are scattered a few isolated spheroidal or stellate cells, which are capable of changing position by virtue of their anioaboid motion. It is usually developed very early ; in the Echinoderms, for example, as early as the blastulastage (fig. 109).
Fig. 109. Two stages of development of Holothuria tubulosa, in optical section (after SELENKA), from BALFOUU.
A, Blastosphere-stage at the end of cleavage.
iur, Micropyle ; ', cliuruui ; *.f, segmentation-cavity, in which gelatinous substance is early .-ecieted as a gelatinous core; bl, blastoderm; e[>, outer, ky, inner germ-layer; ms, amceboid cells arising from the inner germ-layer ; a.c, coelenteron (archenteron).
Into the cavity of the blastula (A ) a homogeneous soft substance, the jelly-core (s.c), is secreted by the epithelial cells. Into this jelly there migrate from the epithelium, and indeed from the particular region which at the time of gastrulation is infolded (fig. 109 B] as the inner germ-layer (hy), numerous cells (ms), which loose their epithelial character, and send out processes in the manner of lymphcorpuscles. They soon distribute themselves as migratory cells everywhere in the jelly.
In the gastrula-stage and subsequently, the cell-containing jelly between the outer and the inner germ-layers represents a third sheet, which is distinguished from the latter histologically, and, according to the definition previously given, cannot be designated as a middle germ-layer ; for by that definition we understand the term to be limited to a sheet of embryonic cells, having an epithelial arrangement and bounding a surface. The jelly-like sheet is a product of the germ-layers, which may be distinguished from them by the name mesenchyme or intermediate layer (Zwischenblatt).
Once formed, the mesenchyme continues to grow as an independent tissue, in that the cells which at first migrated into the jelly at a definite stage of development, to which one may give the name mesenchy?ne-yerni, continue to increase uninterruptedly by means of cell-division. In its growth it penetrates into all the interstices which arise when the germ-layers, as happens in many Coelenterates, produce the most complicated structures by the formation of folds and evaginations ; it furnishes everywhere a support for the epithelial layers which repose upon it. At the same time some of the mesenchyme-cells can alter their original histological character as simple trophic or nutritive cells of the intermediate substance. Thus here and there they differentiate contractile substance at their surface, and become, as is to be seen in Ctenophores and Echinoderms, smooth muscle-cells, the ends terminating either in one fine point, or dividing themselves into several processes, as is more frequently the case with Invertebrates.
In Vertebrates also, after the two primary germ-layers have arisen, a process similar to that which we have just considered appears to lead to the formation of connective tissue and blood, two tissues which correspond morphologically and physiologically to the mesenchyme of Invertebrates.
In the first two editions of the " Lehrbuch " I set forth that the whole mesenchyme-question. in the Vertebrates was still in a nascent condition, that the account therefore presented nothing final, but bore in many respects the character of the provisional. Since that time an essential advance has been made in this field. Thanks to the investigations of HATSCHEK and HABL, of RUCKERT, ZIEGLER, and VAN WIJHE, we have acquired more accurate explanations concerning the origin of the connective substances ; the question of the origin of the vascular endothelium and of the blood, on the contrary, is one that is less cleared up. This determines me to treat the two questions separately in the following account.
The Origin of the Connective Tissues
Selachian embryos appear to be the most suitable objects on which to trace the origin of the connective substances. Here the middle germ-layer serves as the matrix for the mesenchymatic tissue. At the time when the primitive segment is still connected below with the lateral plates, and when the body-cavity is visible in the latter, there appears a cell-growth at the lower border of each primitive segment on the side which is directed toward the chorda. It is ordinarily designated as sclerotome. It contains at first a small evagination of the body-cavity (fig. 258 A sk). At the restricted place designated, which is marked off from its surroundings, and which recurs on each primitive segment, cells in large numbers (fig. 110 sk) individually detach themselves from the epithelial layer, remove by active migration from their place of origin, like the mesenchymatic cells of Invertebrates, and distribute themselves in the space which is limited on the one side by the inner wall (mp) of the primitive segment, and on the other by the chorda (ch) and the neural tube (nr).
At the time of their appearance the amoeboid cells are separated by only a small amount of inter-cellular substance : they increase rapidly in number, and thereby soon crowd chorda, neural tube, and primitive segment farther apart (fig. 111). The segmental arrangement which the growths exhibit at their first appearance (fig. 195 Vr) very early ceases to exist, since by their extension they become fused together into a continuous sheet.
The mesenchyme, which thus grows forth out of the middle germlayer on both sides of the chorda, furnishes the foundation for the ivhole axial skeleton ; it produces the skeletogenous tissue by the growing toward each other and the fusion of the masses which are formed on the right and left sides. As fig. Ill shows, the mesenchyme (sk) grows around the chorda (ch) both dorsally and ventrally, and envelops it with a connective-tissue sheath, which is continually becoming thicker. In the same manner it encloses the neural tube (nr) and forms the membrana reuniens superior of the older embryologists, the foundation out of which subsequently the connectivetissue envelopes of the neural tube and the vertebral arches with their ligaments are differentiated.
Conditions similar to thoss of Selachians are also to be observed, although less distinctly, in Reptiles, Birds, and Mammals ; they have been described by REMAK, KOLLIKER, and others, and have been brought into connection with the formation of the vertebral column. The primitive segments, which are at first solid, soon acquire a small cavity (fig. 116), around which the cells are arranged into a continuous epithelium. Then a part of the wall of the primitive segment lying at its lower and median angle begins to grow with extraordinary rapidity, and to furnish a mass of embryonic connective tissue, which spreads itself around the chorda and neural tube in the manner previously described. The dorsal and lateral parts of the primitive segment (fig. 116 ms), which subsequently loses its cavity, are not involved in this growth ; out of them arise principally the fundaments of the trunk-musculature. This part is consequently now distinguished as muscle-plate (ms).
Figs. 110 and 111. Diagrams of cross sections through younger and older Selachian embryos to illustrate the development of the principal products of the middle germ-layer. After VAN WIJHE, with some changes.
Fig. 110. Cross section through the region of the pronephros of an embryo, in which the myotomes (//<y) are in process of being constricted off.
Fig. 111.- Cross section through a somewhat older embryo, in which the myotomes have just been detached.
nr, Neural tube; ch, chortla ; ao, aorta; sch, subnotochordal rod; mp, muscle-plate of the primitive segment ; 10, zone of growth, at which the muscle-plate bends over into the cutisplate (cp) ; vb, portion connecting the primitive segment with the [walls of the] body-cavity, out of which are developed, among other things, the mesonephric tubules uk (fig. Ill) ; Kk, skeletogenous tissue, which arises as an outgrowth from the median wall of the connecting portion (rb) ; rn, pronephros ; mk l , parietal, mk", visceral middle layer, from the walls of which mesenchyme is developed ; Ih, body-cavity ; Ik, entoderni ; h, cavity of the primitive segment ; uk, mesonephric tubule, arisen from the connecting portion vb of the diagram 110 ; uk 1 , place where the mesonephric tubule has detached itself from the primitive segment ; v.g, mesonephric duct, with which the mesonephric tubule has united on the left side; tr, union of the mesonephric tubule with the body-cavity (nephridial funnel) ; //;', mes 2 , mesenchyme, which has arisen from the parietal and visceral lamellae of the middle layer respectively.
Mesenchyme arises from three other places of the middle germlayer besides the primitive segments from the visceral lamella, from the parietal lamella, and finally from that wall of the primitive segment which is turned toward the epidermis and has been given by RABL the name cutis-plate. Here also the conditions are best followed in Selachii.
Individual cells migrate out from the visceral lamella (Darmfaserblatt), which in early stages is composed partly of cubical, partly of cylindrical cells (fig. 110 mk*\ and distribute themselves upon the surface of the entodermic layer ; they are found at places where no trace of a vessel is observable. They furnish the meseiichyma of the intestinal wall, which is ever becoming more abundant, and which is subsequently converted partly into connective tissue, partly into the smooth muscle-cells of the tunica muscularis (fig. Ill mes 2 ).
A similar process is repeated in the parietal lamella (Hautfaserblatt). Emigrating cells produce between the epithelium of the body-cavity and that of the epidermis an intermediate layer of meseiichyme-cells (fig. 110 mk l , fig. Ill mes 1 ).
An important region for the production of connective tissue is, finally, the cutis-plate, i.e., the epithelial layer of the original primitive segment, which is in contact with the epidermis (fig. 110 cp]. The process occurs here later than at the other places mentioned, and begins with an active cell-growth, which gradually leads to a complete disintegration of the epithelial lamella. " The disintegration," as RABL remarks, " proceeds in such a manner that the cells, which hitherto exhibited an epithelial character, separate themselves from one another, and thereby lose their epithelial character." It is probably from this part of the mesenchyme that the corium is derived.
That the mesenchyme-cells scattered between the epithelial lamellae are capable of executing extensive migrations, after the fashion of migratory cells, is perhaps best shown in the investigation of transparent embryos of Bony Fishes. " One sees distinctly," thus WENKEBACH describes it, "how the cells by means of amoeboid motions, and of sometimes extraordinarily long protoplasmic processes, move themselves about independently in the body of the embryo and upon the yolk, which is not yet clothed with hypoblast, and creep toward definite places, as if they acted voluntarily and consciously." By virtue of this peculiarity, the mesenchyme-cells actively penetrate into all larger and smaller fissures which exist between the germ-layers and the fundaments of organs which have arisen from them. Everywhere they form a filling and connectingmass between these structures, which afterwards acquires a still greater importance as the bearer of blood- and lymph-courses as well as nerves.
In comparison with the earlier editions of the " Lehrbuch," I have here given an essentially different presentation of the development of the mesencliyrne. Formerly, supported by the investigations of His, WALDEYEE, KOLLMANN, and others on meroblastic eggs, I thought it necessary to refer the chief source of the mesenchyme to a limited territory of the germ, to the area opaca, and made the cell-material arise by delamination from the entodermic layer, especially from the yolk-wall. But now I assume a manifold origin from various regions of the middle germ-layer. Thus I come back again to an interpretation which I had already propounded as probable in " Die Ccelomtheorie (p. 80) and "Die Entwickelung des mittleren Keimblattes " (p. 122), to the interpretation, namely, that mesenchyme-gernis in Vertebrates are perhaps formed by an emigration of cells at several distinct places at the same time. Whether this or that be the real mode, the essence of the mesenchyma-theory is not thereby affected, for the essential part of that theory consists in this, that it establishes in the earliest development of tissue a contrast between the epithelial germ-layers and a packing tissue, produced by a dissolution of the epithelial continuity, which spreads itself out between the germ-layers, and soon appears as an independent structure.
Indeed, with this theory as a basis, it would not be surprising it the production of mesenchymatic tissue should not le limited singly to the middle germlayer, and if the entoderm by the contribution of cell-material should participate in its formation.
The Origin of the Vascular Endothelia and the Blood
The question of the origin of the tissues represented in the above heading is one of the most obscure in the realm of comparative embryology. The very investigators who have endeavored most recently and with the most reliable methods to elucidate this matter do not hesitate to emphasise the uncertainty in the interpretation of the conditions presented to them. Even the lowest Vertebrate, which is distinguished by the greater simplicity of its structure, and by the greater ease with which all its processes of development are understood, has failed us in this question. For HATSCHEK, who knows the development of Amphioxus better than any one else, designates the blood-vessels as the only system of organs concerning which he was unable to arrive at a clear understanding.
Consequently in the field now to be examined there are many views and observations which in part stand in the most direct antagonism to each other. To give a comprehensive review of them is not possible without the greatest fulness, which would be contrary to the plan of this Text-book; I therefore limit myself, first, to giving a survey of the various possibilities by which the origin of the vessels and the blood might take place, and, secondly, to presenting a series of observations which have been made on Selachians, Birds, and Mammals ; still it is always to be kept in mind that much remains doubtful here, and that coming years may bring about many a change in our interpretations.
According to one view, the vascular cavities are developed out of fissure-like spaces between the germ-layers which remain unoccupied at the time the fundament of the mesenchyme is produced. These cavities acquire a boundary in this way : the neighboring mesenchyme-cells begin to penetrate into them, and then unite into a vascular endothelium. " The system of blood-vessels and that of lymphatic vessels," observes ZIEGLER, " are produced in their first fundaments from remnants of the primary body-cavity (the space between the primary germ-layers), which at the general distribution of the formative tissue (mesenchyma) remain behind as vessels, lacunae, or interstices, and are enclosed by that tissue and incorporated in it." The formed elements [corpuscles] arise at separate places in the blood-courses by the growth and detachment of mesenchymatic cells.
According to another view, the vessels are constructed in this manner : cells in the mesenchymatic tissue arrange themselves in rows, and these cell-cords become hollowed out ; thereby the more superficial cells furnish the endothelial wall, whereas the remaining cells become blood-corpuscles. The blood-vessels are therefore nothing else than cavities which have been secondarily produced in the mesenchymatic tissues by means of their own cells. Both views agree in this, that they cause the group of sustentative substances to be brought into genetic connection with the blood, and the latter f o figure as a product of the metamorphosis of the mesenchyma.
Moreover, both views may present variations in the details, according as they ascribe to the mesenchyme a different origin and make it arise either out of the middle germ -layer alone, or out of the entoblast alone, or by the migration of cells out of both layers and their union into a single fundament. Still other variations result from the first fundament of the blood-course being sometimes referred to a limited territory of the germ, sometimes to several places. Thus, for the meroblastic eggs of Birds, the area opaca is designated by some observers as the place where vessels and blood are first formed. From here they grow out as it were at first into the embryonic body proper. The opposite is reported of Bony Fishes, in which the first vessels, heart, aorta, caudal veins, and sub-intestinal veins, together with blood-corpuscles, arise earliest in the embryonic body itself, whereas they appear on the yolk only subsequently. Finally, for the Selachians a local origin of the vessels is maintained both for the area opaca and also for the embryonic body in the restricted sense.
In opposition to the two views hitherto presented, a third view assumes a separate origin for the connective substances on the one hand, and for the vascular endothelium and the blood on the other. Whereas the former are produced by the emigration of cells from the middle germ-layer, the vascular endothelium is maintained to arise from cells of the entoblast. It is held that an endothelial sac is formed (perhaps by constriction) as an independent fundament, which by budding gives rise to the whole vascular system.
After this brief survey of the various possibilities concerning the origin of the blood-course, I turn to a description of certain conditions, concerning the signification of which it must be admitted that the views are also often very divergent.
The area opcica of the meroblastic eggs of Fishes, Reptiles, and Birds has always played an important role in the literature on the question of the origin of the blood. Notwithstanding the frequency with which it has been investigated, the researches concerning it cannot be regarded as concluded. It is from this standpoint that I beg the reader to judge what follows.
In the case of the Chick, on which especially we shall base our account, the opaque area is composed of only the two primary germlayers at the time when the middle germ-layer begins to be formed from the region of the blastopore by the production of folds.
The outer germ-layer, as has already been described in Chapter V., has in general a simple structure, since it is composed of a single layer of small cubical cells. The inner germ-layer (fig. 56 ik and fig. 112), on the contrary, alters its condition the more we approach the margin of the disc. In the area pellucida and in the immediately surrounding parts it appears as a single layer of greatly flattened cells, and is separated from the yolk-floor by a cavity filled with an albuminous fluid ; in the opaque area it reposes directly upon the yolk ; its cells nere become higher, cubical, or polygonal, and finally it terminates with a greatly thickened marginal zone, the previously mentioned yolk- wall (dw). This is the important region of the germ with which we now have especially to deal.
The yolk-wall consists in the Chick partly of embryonic cells, which are separable from one another, partly of yolk-material in which are enclosed numerous large and small nuclei enveloped in protoplasm (the merocytes), as at the final stages of the process of cleavage.
Such free nuclei have also been demonstrated with perfect certainty in the marginal territory of the yolk during the course of the formation of the germ-layers in Selachians, Teleosts, and Reptiles (KUPFFER, HOFFMANN, RUCKERT, STRAHL, SWAEN).
The most accurate description of the yolk-nuclei has been given by RUCKERT for the eggs of Selachians (fig. 113). They are present in this case at the marginal portion of the germ-disc, embedded in the yolk in not inconsiderable numbers, and are remarkable for their size, sometimes reaching a diameter ten-fold as great as that of an ordinary nucleus (& 1 , &*). From the protoplasm enveloping the nucleus k* there proceeds a richly branched network of processes. In the interstices of the net are lodged yolk-elements (d) in great numbers, from the size of the ordinary yolk-plates down to the finest granules. The former are often in process of disintegration. One may conclude from this, as well as from other phenomena, that a vigorous consumption of deutoplasm is taking place at the margin of the germ. This deutoplasm is taken up as nutritive material by the protoplasmic net surrounding the nucleus, and employed by means of Ultra-cellular digestion for its growth. Consequently one also sees the yolk-nuclei in active increase.
Fig. 112. Section through the margin of the germinal disc of a Hen's egg incubated for six hours, after DUVAL.
ak, Outer germ-layer ; dz, yolk-cells ; dk, yolk-nuclei ; dw, yolk-wall.
Toward the surface of the yolk small clusters of nuclei (fig. 113 arise out of the large deeper-lying yolk-nuclei. From these there are finally produced genuine cells of the germ (2), by the small nuclei surrounded by a layer of protoplasm detaching themselves from, the yolk, as it were by an act of supplementary cleavage. ' : Since the merocytes thus on the one hand uninterruptedly take up nutritive material out of the yolk, and on the other continually surrender it in the form of cells to the germ-layers of the nascent embryo, they present an important link between the latter and the yolk" (RUCKERT.)
Pig. 113. Yolk-nuclei (merocytes) from Pristiurus, lying underneath the germ-cavity B, after RCCKF.RT.
- , Emltryonic cells ; /, superficial cle;ir nuclei ; i -1 , deeper nuclei ; ^*, nnirginal nuclei rich in chromatin, largely freed from the surrounding yolk, in order to show the processes of the protoplasmic mantle ; d, yolk-plates.
The views of investigators on the significance of the yolk-wall and of the merocytes enclosed in it are very divergent. Indeed there is unanimity only in this, that the yolk-wall contributes to the increase of the lower germ-layer by single cells becoming independent and attaching themselves at the margin to the elements which already have an epithelial arrangement. On the other hand it appears less certain how far the yolk-wall is concerned in the formation of the blood. According to the observations of His, DISSE, RAUBER, KOLLMANN, RUCKERT, SWAEN, GENSCH, HOFFMANN, and others, it does share in this process during a limited period of development in the case of Selachians, Teleosts, Reptiles, and Birds.
In the Selachians the anterior margin of the germ-disc is the first to be metamorphosed into a vascular zone. RUCKERT could find here numerous and unequivocal indications that the previously described peculiar cell-elements of the yolk (merocytes) provided with large nuclei contribute to the formation of blood-islands, in that they break up into clusters of small cells, detach themselves from the yolk-containing part of the lower germ-layer, and become differentiated on the one hand into the migratory cells of the first blood-vessels, and on the other into the blood-corpuscles. RUCKERT further maintains that the material destined for the production of blood is supplemented by means of cells freshly cleft off from the yolk.
SWAEN remarks with the same positiveness, " Les premiers ilots sanguins se developpent aux depens des elements de Vhypoblaste. Ces derniers constituent a la fin de ce developpement les parois de cavites vasculaires closes et les cellules sanguines qui les remplissent." Likewise GENSCH makes the large cells in the yolk responsible for the formation of the blood in the case of the Bony Fishes. HOFFMANN also finds in Reptiles that the blood and the endothelial wall of the vessels, as well a,s the spindle-shaped cells which lie between the vessels, are a product of the inner germ-layer, and that they appear at definite places of the germ-disc at a time when the middle germ-layer has not yet been formed in those regions.
Finally, it is stated concerning the germ of the Chick that at the end of the first day of incubation the cells in the yolk-wall have become very numerous, through the multiplication of the nuclei enclosed in the latter, and that afterwards the abundance of the cells diminishes. For part of the cells which have been formed by the active proliferation now detach themselves from the yolkwall, get into the space between the outer and inner germ-layers, and there produce a third independent layer, which is continually increasing in thickness, whereas the remaining part becomes modified into an epithelium of large cylindrical cells containing yolkgranules. This middle layer is judged by several investigators to be an independent fundament of the germ, and has in this sense been described by His as parablast, by DISSE and others as vascular layer, by RAUBER as desmohcemoblast, and by KOLLMANN as marginal germ or acroblast.
All of these accounts need still more precise confirmation, since they have often been called in question, even up to most recent times. Thus KOLLIKER has always defended the position that not only the connective substances, but also the vessels and the blood, are products of the middle germ-layer, and are generated by it in its peripheral regions. KASTSCHENKO, in his study of the Selachii, could not convince himself that the merocytes have special importance in the formation of blood and vessels, but was not, however, willing to deny it. So much the more positively do WENKEBACH and ZIEGLER, on the strength of their investigations on Teleosts, express themselves against the mode of blood-formation given by GENSCH. According to ZIEGLER, the blood-corpuscles are developed in the blood-vessels of the embryonic body itself. The free nuclei of the yolk, the merocytes, on the contrary, it is maintained, do not share in the formation of embryonic tissues, but, in adaptation to the function of resorbing the yolk, undergo peculiar modifications, which " cause the frequently affirmed but never proved production of blood-corpuscles [by them] to appear improbable." Under this condition of affairs, I must regard the question of the source of the cell-layer in which, in the region of the opaque area, the formation of blood takes place as not yet ready for final judgment.
So far as regards the further changes, by means of which the cell-layer under consideration is converted into connective substance and blood, on the whole I subscribe, in this difficult field of investigation, to KOLLIKER'S representation.
At the end of the first day of incubation, the masses of cells which lie between the inner :md the outer germ-layers arrange themselves in cylindrical or irregularly limited cords, which join themselves together into a close-meshed network; they are the first fundaments both of the vessels and also of their contents, the blood. In the spaces of the net are to be found groups of indifferent cells, which afterwards become embryonic connective tissue, and which are the Substanzinseln (fig. 114) of authors.
At the beginning of the second day of incubation, the solid fundaments of the vessels become more distinct, in proportion as they become bounded superficially by a special wall, and acquire an internal cavity. The wall of the vessels is developed out of the most superficial cells of the cords, and is composed during the first days of incubation of a single layer of very much flattened polygonal elements, on account of which the first vessels of the embryo are often designated as endothelial tubes (fig. 114 and fig. 115 gw}.
The cavity of the vessel is probably formed by the penetration of fluid into the originally solid cord from its surroundings, thus forming the plasma of the blood, by which the cells are pressed apart and to the sides. The cells then constitute here and there thickenings of the wall, and project into the fluid-filled cavities as elevations of loosely united spherical elements (fig. 114, Blood-islands). Consequently the vessels which are just becoming permeable are very irregular, since narrow places and wider ones, often provided with
tions, alternate (fig. 114) with one another, and since the vessels are sometimes wholly excavated, fluid-filled, en d o t heli al tubes, a n d sometimes remain more or less impassable, owing to the variously formed cell aggregates which project from the wall.
The aggregations of cells themselves are simply the centres where the formed components of the blood are produced . The small spherical nucleated cells, which still enclose dark yolkgranules, become at first homogenenus
Fig. 114. A portion of the vascular area of the germ-disc of an embryo Chick, in which 12 primitive segments are developed, after DISSE.
One sees the more darkly shaded blood-courses, in which lie the "blood-islands," the centres whence the blood-corpuscles arise. The clear spaces in the vascular netwoi'k, the walls of which are formed of flat endothelial cells, are the " substance-islands " (Substanzinselu).
by the dissolution of the latter, and then, owing to the formation of the coloring matter of the blood in them, they take on a slightly yellowish color, which gradually becomes more intense.
If one at this time examines a blastoderm which has been removed from the yolk, the zone in which the formation of blood takes place appears flecked with more or less intensely colored blood-red spots, some of which are roundish, others elongated, and others branched. The spots are known as the "blood-points or blood-islands of the blastoderm (fig. 114). From these formative areas the superficial cells now detach themselves and enter the blood-fluid as the isolated red blood-corpuscles. Here, as well as in the blood-islands, they multiply by means of cell-division, during which the nucleus is metamorphosed into the well-known spindle-figure.
As HEMAK first showed, divisions of blood-cells are to be observed in the Chick in great numbers up to the sixth clay of incubation, whereas they later become more rare, and then wholly disappear. Also in the case of Mammals nd <;f lfn (For.) the first embryonic blood-corpuscles, which are at this time provided as in the other Vertebrates with a genuine cell-nucleus, 2)ossess the power of division.
Fig. 115. Cross section through a portion of the vascular area, after DISSE.
ok, Outer, ik, inner germ-layer ; ;,ik\ parietal, //</., visceral lamella of the middle germ-layer ; lh t extra-embryonic body-cavity ; git>, wall of blood-vessel formed of endothelium ; bl, bloodcells ; g, vessels.
In proportion as blood-corpuscles still further detach themselves from the blood-points, the latter become smaller and smaller, and finally disappear altogether ; but the vessels without exception then contain, instead of a clear fluid, red blood with abundant formed elements (fig. 115 bl).
Subsequently there occur changes in the Substanzinseln which lead to the formation of embryonic connective substance. The germinal cells, at first spheroidal, separate farther from one another, at the same time secreting a homogeneous inter-cellular substance ; they become stellate (fig. 116 sp), and send out processes by means of which they are united into a network, which stretches all through the gelatinous secretion ; other cells apply themselves to the endothelial tubes of the vessels.
After the formation of vessels and blood is completed, the territory of the area opaca, in which the processes just described take place, is sharply delimited at its periphery (fig. 117) in all meroblastic eggs, as well as in those of Mammals. HV>r the dose network of blood vessels ends abruptly at its periphery in a broad, circular, marginal vein (the vena or sinus terminalis, S.T.).
Beyond the sinus terminalis, there is formed on the yolk neither blood nor blood-vessels. Nevertheless, the two primary germ-layers spread themselves out laterally over the yolk still farther, the outer layer more rapidly than the inner, until they have grown entirely around it.
We must therefore now distinguish in the opaque area (Plate I., fig. 2, page 213) two ring-like areas, the vascular area- (gh} and the yolk-firca (dh), area vasculosa and area ritcllina. Since, moreover, the area pellucida is still recognisable, being traversed by only a few chief trunks of blood-vessels leading to the embryo, the body of the embryo is enclosed altogether by three zones or areas of the extraembryonic part of the germ-layers.
Fig. 117. Diagram of the vascular system of the yolk-sac at the end of the third day of incubation, after BALFOUR.
The whole blastoderm has been removed from the egg and is represented as seen from below. Therefore what is really on the left appears on the right, and rice vtrsu. The part of the area opaca in which the fine vascular network has been formed is sharply limited at the periphery by the sinus terminalis, and represents the vascular area ; outside of it lies the yolk-area. The immediate vicinity of the embryo is destitute of a vascular network, and is designated now, as at an earlier stage, by the name area pellucida.
77 Heart; AA, aortic arches; Ao, dorsal aorta; L.Of.A, left, R.Of.A, right vitelline artery; S.T, sinus terminalis ; L.Of, left, R. Of, right vitelline vein ; S. V, sinus venosus ; D.C, ductus Cuvieri ; S.Ca.V, superior, V.Ca, inferior cardinal vein. The veins are drawn in outline, the arteries in solid black.
Up to the present we have pursued the formation of blood in the opaque area. But how do the vessels in the body of the embryo itself arise ? Here, too, the uncertainty of our present knowledge is to be emphasised.
According to the representation of His, to which KOLLIKER also adheres, and which the author himself has made the foundation of his account in the first edition of this Text-book, blood-vessels in the embryo are not independently formed, but tnke their origin from those already existing in the opaque area. According to His, the germ of the blood and connective substances, originally a peripheral fundament, makes its way from the opaque area at first into the pellucid area, and from there into the body of the embryo itself, and is distributed everywhere in the spaces between the epithelial germ-layers and the products that have arisen by constriction from them. Into the spaces migrate first of all amoeboid cells, which send out in front of them branched processes ; on the heels of these follow endothelial vascular shoots.
At variance with the teachings of His are noteworthy investigations of recent date, not only the previously mentioned accounts of the manifold origin of the connective substances from the middle germ-layers, but also particularly the more recent observations con cerning the independent origin of vessels and the endothelial sac of the heart in the body of the embryo itself. (RUCKERT, ZIEGLER, MAYER, RABL, KASTSCHENKO, and others.) For Selachian embryos the question, whether the repository of the material for the blood-vessels of the embryo is to be sought exclusively on the nutritive yolk, is, as RUCKERT remarks, to be answered definitely in the negative. The vessels arise in the embryo itself within the territory of the mesenchyme, from cells which are sometimes loosely, sometimes compactly arranged (RtiCKERT, MAYER).
RUCKERT derives the cells that form the vessels from two different sources, partly from the inner germ-layer of the yolk-wall, partly from the adjoining mesoblast, and their double origin appears to him a natural process of development, in so far as the two layers which bound the first vessels also furnish the material for their walls.
To the same purport are the accounts concerning the formation of the endothelial sac of the heart. At first it consists of a rather irregular mass of cells, in which there appear separate cavities, that gradually unite to form a single cardiac space. The cell-material of the fundament of the heart is developed in situ (RUCKERT, ZIEGLER, MAYER, RABL, and of the earlier investigators GO'TTE, BALFOUR, HOFFMANN) from the wall of the bounding germ-layers ; however, uncertainty prevails as to whether the inner germ-layer alone, or the middle, or both, are concerned in the production of the fundament.
When once the first vessels have been formed, they grow further independently, and continually give rise to new lateral branches by means of a kind of budding process.
It can be observed that from the walls of vessels that are already hollow, solid, slender sprouts go out, which are formed of spindleshaped cells, and by means of cross-branches join others to form a network. The youngest and most delicate of these sprouts consist of only a few cells arranged in a row, or indeed of only a single one, which, reposing upon the endothelial tube like a knob, is drawn out into a long protoplasmic filament. Into the solid sprout there now projects from the already completed vessel a small evagination, which gradually elongates and at the same time enlarges into a tube, the wall of which is formed of the separated cells of the fundament. The formation of blood-corpuscles no longer takes place in this process, all the cells of the sprout being employed to form the wall of the vessel. Since out of the vessels thus produced new sprouts are formed, and so on, the fundaments of the vessels spread themselves out everywhere in the spaces between the germ-layers and the organs which have by constrictions been formed from them.
There are, moreover, two different opinions about the manner in which the sprouting takes place. Are the solid vascular shoots formed exclusively by growth of cells in the wall of the eudothelial tube, or do neighboring connective-tissue cells take part in their formation ? While RABL holds to the proposition that new vascular endothelia always take their origin from such as are already in existence, KOLLIKER, MAYER, and RUCKERT make statements which appear to prove that the endothelial vascular tubes both continue to grow by themselves alone, and also to elongate through the participation of the connective-tissue cells of the surrounding tissue.
In the preceding pages we have endeavored to show in detail how in Vertebrates the material of the cleavage- cells is differentiated into the separate fundamental or primitive organs. As such we must designate the outer and the inner germ-layers, the two middle germ-layers, and the mesenchyme or intermediate layer.
In order properly to estimate at once the significance and the role of these fundamental organs, we will glance at the final result of the process of development propound the question. What organs and tissues take their origin in the separate germ-layers and the mesenchyme ? A definite answer to this question is possible, except 011 a few points concerning which the accounts of the different observers arc still contradictory, and which therefore will bo indicated by a mark of interrogation.
From the outer germ-layer arise : the epidermis, the epidermoidal organs, such as hair and nails, the epithelial cells of the dermal glands, the whole central nervous system with the spinal ganglia, the peripheral nervous system (?), the epithelium of the sensory organs (eye, ear, nose), and the lens of the eye.
The primary inner germ-layer is differentiated into : 1. The secondary inner germ-layer, or entoblast ; 2. The middle germ -layers ; 3. The fundament of the chorda ; 4. The germ of the mesenchyme, which forms the intermediate layer.
The entoblast (Darmdriisenblatt) furnishes the epithelial lining of the whole intestinal canal and its glandular appendages (lung, liver, pancreas), the epithelium of the urinary bladder, and the taste buds.
The middle germ-layers undergo extremely various metamorphoses after having been differentiated into primitive segments and lateral plates.
From the primitive segments are derived the striated, voluntary muscles of the body and a part of the mesenchyme.
Prom the lateral plates arise the epithelium of the pleuroperitoneal cavity ; the epithelium of ovary and testis (primitive ova, mothercells of the spermatozoa) ; in general, the epithelial components of the sexual glands and their ducts, as well as those of the kidney and ureter ; and finally mesenchymatic tissue.
The fundament of the chorda becomes the chorda dorsalis, which in the higher Vertebrates is reduced, during later stages of development, to insignificant remnants.
The mesenchyme-germs, which produce the intermediate layer, undergo manifold differentiations, for they spread themselves out in the body between the epithelial components as the intermediate mass. From them are derived : the multiform group of sustentative (connective) tissues (mucous tissue, fibrillar connective tissue, cartilage, bone), vessels (?) and blood (?), the lymphoid organs, the smooth, involuntary muscles of the vessels, of the intestine, and of various other organs.
HISTORY OF THE PARABLAST- AND MESENCHYME-THEORIES.
The older investigators, as, for example, REMAK, grouped together all the cells which are inserted between the two primary germ-layers under the common name of the middle germ-layer, and assumed for them a common origin. To this conception His opposed in the year 1868 in " Die erste Entwicklung des Hiihnchens im Ei " his " parablast-tlieory" in which, influenced principally by histogenetic considerations, he distinguished two fundaments of different origin, an archiblastic and a parablastic.
As archiblastic fundament he designated the part of the middle gerni-layer which lies in the body of the embryo itself, the axial cord (Achsenstrang) and the animal and vegetative muscle-plates, and he made them arise by clelaminatioii from the primary germ-layers, and therefore ultimately from the embryonic cleavage-cells.
He gave the name parablast to a peripheral fundament, lying originally outside the embryo, which is the source of all the connective substances, the blood and the vascular endothelium, and which grows from the margin, or more specifically from the opaque area, into the body between the archiblastic tissues.
The division of the middle germ-layer into archiblast (chief germ) and parablast (accessory germ), proposed by His and carried out in several of his writings, found at the time no approbation, and encountered decided and successful opposition, especially on the part of HAECKEL, because the correct views contained in the doctrine were obscured and covered up by peculiar conceptions about the origin of the parablast. The parablast, it was claimed, is not derived from the egg-cell, but from the white yolk, a product of the granulosa-cells, which, according to the earlier teachings of His, penetrate into the primordial ovum in great numbers and become the white yolk-cells and the yellow spherules. But the granulosa-cells in turn, it was maintained, arise from the connective tissue (leucocytes) of the mother ; consequently after their migration into the egg they are capable of producing again only connective tissue and blood.
His thought it was necessary to assume a fundamental difference between chief germ and accessory germ ; the former alone had experienced the influence of fertilisation, since it alone was descended from cleavage-cells, whereas the latter, since it issued from the white yolk (a derivative of the maternal connective tissue), was " purely a maternal dower." EAUBER, in a short communication, accepted the conclusions of His, in so far as he also assumed a common origin for blood and connective tissue, a special " haarno-desmoblast," but differed from him in that he derived them from the cleavage-cells.
GOETTE (1874) is also to be mentioned in this connection, since he maintained that the blood is developed out of yolk-cells, which break up into clusters of smaller cells (Amphibia and Birds).
Proceeding from other standpoints, and induced by observations on Invertebrates, my brother and I were led in our Ccelom-Theory (1881) to a result similar to that of His, namely, that two entirely different structures had been hitherto embraced under the expression middle germ-layer, and that it was necessary to introduce in the place of the old indefinite conception two new and more precise ones, " middle germ-layer in the restricted sense " and " mesenchyme-germ." But our conception, notwithstanding many points of agreement, took in detail a form very different from the doctrine of His.
All fundaments of the animal body are derived from embryonic cells, which have been produced from the egg-cell by the process of cleavage. The distinction between middle germ-layer and mesenchyme-germ is to be sought in another direction than in that indicated by His. The middle germ-layers are sheets of embryonic cells, having an epithelial arrangement, which arise bij a process of folding from the inner germ-layer, just as the latter does by a fold ing df the blastula (compare the historical part of Chapter VII.). The mesenchymatic germ, on the contrary, embraces cells, which have been individually <1 ft ached from epithelial union in the inner germ-layer, and furnish the foundation for connective substance and blood by spreading themselves out in the system of spaces between the epithelial germ-layers.
After the appearance of the Ccelom-Theory, His entered again into an explanation of his parablast-theory, and modified it in his paper, " Die Lehre vom Bindesubstanzkeirn," in so far as he no longer laid weight on the question whether the fundament of the connective substance was derived from the segmented or the unsegmented germ.
The theory of the double origin of the middle germ-layers, established by His and by us in different ways, met with opposition on the part of KOLLIKER who held to the older interpretation ; but by many others it was accepted : attempts were made further to confirm and also to modify it by KUPFFEE, DISSE, WALDEYER, KOLLMANN, HEAPE, and others, who defended the existence of a special connective-tissue germ.
KUPFFEE and his followers furnished important observations concerning the presence of yolk-nuclei in a definite zone of the embryonic fundament, and their relation to the formation of blood in Fishes and Eeptiles.
HOFFMANN and RUCKERT showed that the yolk-nuclei do not arise by free [spontaneous] formation of nuclei, but are descendants of the cleavage-nucleus.
DISSE investigated the germ-wall of the Hen's egg.
KOLLMANN named the cells which migrate out between the germ-layers poreuts (Poreuten), and the whole fundament the acroblast.
Finally, WALDEYER endeavored to derive the connective-tissue germ from a special part of the cleavage -material, which he divided into an archiblast and a parablast.
According to WALDEYER' s theory, the cleavage of the eggs of all those animals in which there is any blood and connective substance does not take place uniformly up to the end, but one must distinguish a primary and a secondary cleavage. " The former divides the egg, so far as it is in any way capable of cleavage, into a number of cells, which are ready for the production of tissues. These then form the primary germ-layers. A remnant of immature Cleavage -cells (in the case of holoblastic eggs), or of egg-protoplasm, which is not yet converted into the cell-form (in meroblastic eggs), is left remaining. Neither the immature cells, nor the protoplasm still unconverted into cells, enter for the present into the integrating condition of the germlayers. On the contrary, it is only afterwards that there is effected on this material a further formation of cells, the secondary cleavage. The immature cells of the holoblastic eggs, over-loaded with nutritive yolk, divide themselves, or, if one prefers, ' cleave ' themselves further, or the parts which are most richly provided with protoplasm constrict themselves off from the eggs, whereas the remnant of the nutritive material is consumed, the unformed remnants of the protoplasm (germ-processes) of meroblastic eggs become divided up into cells. The cell-material thus secondarily acquired migrates in between the primary germ-layers, and becomes blood and connective substance." According to the recent investigations of EABL, ZIEGLER, VAN WIJHE, RiiCKERT, and others, the mesenchyme is produced from various regions of the middle germ-layer. A participation of the inner germ-layer in the formation of the blood-vessels is rendered probable.
1. Besides the four germ-layers, which have the form of epithelial lamellae, special germs are developed in the higher Vertebrates for the sustentative substances and the blood, the mesenchyme -germs. The latter together make up the intermediate layer.
2. The mesenchyme-germs arise by cells detaching themselves from epithelial union with the germ-layers, and penetrating as migratory cells into the fissure between the four germ -layers (the remnant of the original cleavage-cavity) and spreading themselves out in this space.
3. Germ-layers and mesenchyme -germ (intermediate layer) exhibit a difference in the method of their origin : the former are developed by foldings of the wall of the blastula, the latter by emigration of isolated cells from definite territories of the germ-layers.
4. Mesenchyme-germs arise from the wall of the primitive segment, from the cutis-plate, and at certain regions of the parietal and visceral lamellae of the middle germ-layer.
5. Blood-vessels are developed both in the body of the embryo itself, in a manner which still remains to be accurately determined, and also in the territory of the area opaca of meroblastic eggs.
6. The source of the cells from which the vessels and blood of the opaque area arise is at present a matter of controversy.
7. In the formation of vessels in the opaque area the following phenomena are to be regarded : (a) The embryonic cells of the intermediate layer arrange themselves : First into a network of cords, and Secondly into the substance-islands (Substanzinseln).
(b) There are developed out of the cell-cords, at the same time with the secretion of the fluid portions of the blood, the endothelial wall of the primitive blood-vessels and their cellular contents, the blood-corpuscles (blood-islands).
(c) The Substanzinseln become embryonic connective substance.
(d) The place where blood-vessels and connective substance at first arise in the opaque area is sharply limited at the periphery by a circular vessel, the sinus terminalis.
(e) Since the outer and the inner germ-layers further con tinue to spread themselves out over the yolk after the development of the intermediate layer, the body of the embryo becomes surrounded by three areas : First by the area pellucida, Secondly by the vascular area ending in the sinus terminalis, Thirdly by the yolk-area, which is coextensive with the margin of the overgrowth.
8. The red blood-corpuscles of all Vertebrates possess in the earliest stages of development the power of increase by means of division. The red blood-corpuscles of Mammals have at this time a nucleus.
9. The following table gives a survey of the fundamental organs of the embryo, and the products of their further development : I. Outer Germ-layer.
Epidermis, hair, nails, epithelium of dermal glands, central nervous system, peripheral nervous system, epithelium of sensory organs, the lens.
II. Primary Inner Germ-layer.
1. Entoblast, or secondary inner germ-layer.
Epithelium of the alimentary canal and its glands, epithelium of urinary bladder.
2. Fundament of the chorda.
3. The middle germ-layers.
A. Primitive Segments.
Transversely striped, voluntary muscles of the body. Parts of the mesenchyme.
B. Lateral Plates.
Epithelium of the pleuroperitoneal cavities, the sexual cells and epithelial components of the sexual glands and their outlets, epithelium of kidney and ureters. Parts of the mesenchyme.
4. Mesenchyme- germ.
Group of the connective substances, blood-vessels and blood, lymphoid organs, smooth involuntary muscles.
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Text-Book of the Embryology of Man and Mammals: Description of the Sexual Products | The Phenomena of the Maturation of the Egg and the Process of Fertilisation | The Process of Cleavage | General Discussion of the Principles of Development | The Development of the Two Primary Germ-Layers | The Development of the Two Middle Germ-Layers | History of the Germ-Layer Theory | Development of the Primitive Segments | Development of Connective Substance and Blood | Establishment of the External Form of the Body | The Foetal Membranes of Reptiles and Birds | The Foetal Membranes of Mammals | The Foetal Membranes of Man | The Organs of the Inner Germ-Layer - The Alimentary Tube with its Appended Organs | The Organs of the Outer Germ-Layer | The Development of the Nervous System | The Development of the Sensory Organs | The Development of the Skin and its Accessory Organs | The Organs of the Intermediate Layer or Mesenchyme | The Development of the Blood-vessel System | The Development of the Skeleton
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