Paper - The early morphogenesis and histogenesis of the liver in Sus scrofa domesticus, including notes on the morphogenesis of the ventral pancreas

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Hilton DC. The early morphogenesis and histogenesis of the liver in Sus scrofa domesticus, including notes on the morphogenesis of the ventral pancreas. (1903) Trans. Amer. Microscopical Soc. 24: 55-88.

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The Early Morphogenesis and Histogenesis of the Liver in Sus scrofa domesticus, including notes on the Morphogenesis of the Ventral Pancreas

By David C. Hilton

With Four Plates (1903)

Published under a grant from the Spencer-Tolles Fund


The material used in this research was selected from a collection of five hundred embryos obtained at the packing houses in South Omaha, Nebraska. The embryos ranged in length from 4 to 25 mm. They were taken from the warm uteri, and, while their hearts were beating, placed in killing and fixing reagents. For this purpose different reagents were used, such as picro-nitric acid, chromonitric acid, Zenker’s fluid, formol-acetic acid-alcohol mixture, and 10 per cent formaldehyde. The specimens were hardened in 75 per cent alcohol.

The approximate age and the degree of development of each embryo were determined by counting the protovertebrae and comparing the count and general appearance of the specimen with Keibel’s tables and charts. Measurements furnish very inaccurate data, and are not to be relied on.

Sections of series P and K were cut 6m thick, the others, roy. In all, twenty-five series of sections were studied. Those from which drawings are produced in this paper were stained as follows:

Series X? (Dr. Peterson’s) — borax carmine.

Series D — Grenacher’s alum carmine.

Series G — Ehrlich’s acid haematoxylin, picric acid.

Series J — Ehrlich’s acid haematoxylin.

Series P — borax carmine, picric acid.

Series K — Ehrlich’s acid haematoxylin.

Series S — Grenacher’s alum carmine, picric acid.

All of the above series were killed and fixed in formol-acetic acidalcohol solution. Eleven models of the hepatic proton were constructed at a magnification of 100 X.

Aside from my own material, I have had access, through the kindness of Dr. Peterson, of Omaha, Nebraska, to his sections and models of Series X* which furnished the most primitive stage studied.

I would not close this introduction without expressing my sincere thanks and obligation to Dr. Henry B. Ward, for several years my teacher, whose kindness and helpful suggestions have made this undertaking both pleasant and profitable.


The simple wall of the proton

In so far as this research reveals the morphologic changes that the proton of the liver suffers, there are four distinct stages of formcondition under which it is convenient to discuss the subject.

In the first stage, the proton is a modified strip of the ventral epithelium of the foregut bordering the yolk-stalk; no part of the proton forming as yet an evagination of the enteric canal. In the second stage, a part of the proton forms a shallow evagination. In the third stage, a greater proportion of the proton is included in the now partially subdivided evagination which opens by a broad mouth into the foregut, but no part of the proton borders the yolkstalk. In the fourth stage, the entire proton is an evagination with a complete posterior surface, and it opens by a more or less constricted neck into the lumen of the foregut.

Stage 1 (Fig. 11). At this period of growth, the ventral wall of the foregut where it lies dorsad to the heart extends approximately in an antero-posterior direction (7), but where it approaches the posterior end of the sinus venosus (sv) it arches ventrad, gradually assuming a dorso-ventral attitude posterior to the heart (ht) and postero-ventrad to the sinus venosus. Here the intestinal wall constitutes the lining of the anterior inner surface of the yolk-stalk where it opens into the intestine (ys). At about the level of the ventral aspect of the heart the wall of intestinal epithelium, having tapered to a very thin margin, becomes continuous with the delicate extra-embryonic lining of the yolk-stalk (bys). That portion of the ventral wall of the foregut described as lying behind the heart, and assuming an approximate dorso-ventral direction, is the earliest rudiment of the liver observed. Its greatest thickness is two to three times as great as that of the ordinary epithelial lining of the intestine, and the point at which the intestinal epithelium thickens abruptly, caudad to the sinus venosus, defines the dorsal border of the hepatic proton (bd).

Between the proton and the heart is an area filled with embryonic connective tissue rich in blood supply. This vascular area of tissue is the septum transversum, and that part of it immediately contiguous to the proton is called the prehepaticus (ph). The liver finally comes to be completely within it, and derives its interstitial tissue therefrom.

The sinus venosus is the largest blood space in the septum transversum and is dorsally situated within it (Figs. 11, 12, and 13, sv). Anteriorly it opens into the heart. Posteriorly it comes in close proximity to the dorsal portion of the anterior surface of the proton (Figs. 11, 12, and 13, ds). On each side of the median plane a short extension of the sinus projects posteriad. Each projection is formed by the union of two veins,—the vitelline and umbilical.

The umbilical veins extend in an antero-posterior direction, each lying in the lateral body wall (Fig. 14, vw). The veins of this pair have scarcely any extensions into the septum transversum.

The vitelline veins extend antero-posteriad in the extreme dorsal portion of the septum transversum. There is one at each lateral aspect of the intestine, and for a great part of their length above the liver proton, they are included in folds of the septum transversum which project dorsal into the pleuro-peritoneal cavity (Fig. 14, vv). Large sinus-like extensions from the ventral surface of this latter pair of veins dip into the septum transversum and ramify it with a vascular network (Figs. 14, 15, and 16, sm; also other figures). The higher the stage of development, the more the branches of this network increase in relative number and diameter. Close to the wall of the proton, the vascular spaces are large and more or less sinus-like. These sinuses decrease in size and increase in number toward the more peripheral region of the septum transversum, where they appear more like capillaries.

Minot (98) gives an account of a similar sinus-like structure of the vascular system in the mesonephros of the pig embryo. The vascular spaces in the septum transversum about the proton of the liver agree with the vessels described by Minot in respect to communication, size, irregular curvature, and the make-up of their walls which follow the surface of the liver rods rather than their own and independent curve as is characteristic of true capillaries. Minot states that there is little mesenchyme between the vessels and the tubuli of the mesonephros. About the proton of the liver and the vascular spaces surrounding it there is considerable mesenchyme, but it is not so disposed as to form in any sense a supporting wall for these spaces, with the exception of the sinus venosus. These spaces are often much larger than the vitelline veins with which they communicate (Fig. 14, s#).

According to the foregoing description of the hepatic proton, it may be defined as that thickened portion of the ventral wall of the foregut lying upon the prehepaticus posterior to the heart, and extending in a dorso-ventral direction from a point posterior to the sinus venosus ventrad into the yolk-stalk where it ends, after tapering to a thin border. Its border, on the one hand, is attached in that it is an extension of the intestinal wall (Fig. 11, bd), and, on the other hand, is free where its thin edge ends in the extraembryonic lining of the yolk-stalk (Fig. 11, bys). Of its two surfaces, the inner or lumen surface is in contact with the embryonic fluid within the lumen of the enteric canal and yolk-stalk; the outer surface bounds the prehepaticus posteriorly.

Stage 2 (Figs. 1, 1a, tb). The principal difference between this stage and stage I may be grouped under changes in the thickness, the extent, and the form of the proton.

In thickness, the wall has doubled that found in stage 1. The variations in thickness are numerous and promiscuously distributed, with the exception that along the attached border—that continuous with intestinal epithelium—and along the free border, the wall averages thinner than elsewhere. The free border always tapers to a thin edge, and at this stage flares outwards, causing a depression on the external surface parallel with it.

The extent of the proton has been augmented greatly by addition to the original. This increase has occurred by virtue of two processes. The first is cell proliferation, most obviously indicated by the ventral prolongation of the intestinal wall on the lateral inner surfaces of the yolk-stalk (ys), immediately posterior to the original proton of stage 1. And the second is the differentiation of this intestinal increment into hepatic structure. The differentiation has gradually extended posteriad from the protonic inception. Therefore, posteriorly the hepatic tissue is least mature ; whereas, anteriorly it is most mature. The ventral prolongation of the intestinal wall into the yolk-stalk is greater anteriorly, so that the yolk-stalk border of the proton and of the intestine lying posterior to it, slants postero-dorsad from its more anterior portion.

As to the form of the proton in this stage, a very noteworthy consideration is that to describe it in the terms of a shallow outpocketing of the enteric canal is incomplete. Cut the proton by a plane transverse to a median sagittal section of it, in a line drawn from the most anterior point on its dorsal border where it is continuous with the intestine, to the most anterior point on the free border at the yolk-stalk. Such a plane is inclined dorso-ventrad and slightly posteriad (/d). This divides the proton into two portions. The part anterior to the plane describes a shallow basinlike evagination, which in this model is imperfect on account of the excessive anterior (sinus) depression (ds), although it is seen clearly in other models. The broad mouth of the evaginated portion coincides with the plane, opens posteriorly, and is inclined very slightly dorsad. That part of the proton posterior to the plane is not any part of an evagination. It consists in a posterior alar continuation of each lateral wall of the evagination (ea).

There are the dorsal and the posterior borders. The former extends approximately in an antero-posterior direction. It is Ushaped; the convexity of the U constituting the dorsal border of the anterior surface, and each limb of the U making up the dorsal border of the lateral surface of its own side. This border is attached in that throughout its entire length, the proton is continuous with the intestinal wall.

The latter border is divided into an upper, attached, and a lower, free, portion. Since the difference between the structure of the hepatic tissue and the ordinary intestinal epithelium fades out by degrees posteriorly, it is difficult to determine by a line exactly where the proton ceases and the intestine begins. But this line defining the attached part lies approximately dorso-ventrally on each side, from the intestine above to some point on the free border below. The model (Fig. 1) includes an area about as far posteriad as the location of this border (bp). The lower, free part consists in the thin edge of the proton at the yolk-stalk. It is U-shaped. The arch of the U constitutes the posterior boundary of the ventral surface of the proton. Each limb of the U extends postero-dorsad on its respective side, to that point where it meets the ventral end of the attached portion, being here continuous with the intestinal yolk-stalk border.

There are the internal and external surfaces which have been increased greatly in extent, and have become subdivided into a ventral, an anterior, and two lateral aspects. These surfaces possess a few characteristic features. The anterior surface presents a deep indentation (sinus depression) across its dorsal portion (ds). It is observable in most of the specimens, but not in all (Figs. 1 and 2). This indentation when present subdivides the anterior portion of the proton into two lobes, of which the one lying dorsad to the indentation is the smaller. The lateral surfaces vary considerably in contour. At their anterior and ventral margins they arch into the corresponding surfaces. Their two remaining margins are continuous directly with the intestine, except the free yolk-stalk portion of the posterior margin. The ventral surface, in most cases, is convex where it arches dorsad into the anterior and lateral surfaces, and concave antero-posteriorly where its free border flares downward slightly at the yolk-stalk.

According to most of the models, the diameter of the proton from the ventral border of the intestine above, to the ventral surface of the proton below, is much greater than its dimensions from side to side, although this relation is sometimes reversed (di, dvd).

Three important concomitant changes have taken place with this increase in the number and the extent of borders and surfaces, and enter as factors in producing the difference in form and location between the proton of stage 1 and of stage 2. First, the downgrowth of the wall of the enteric canal along the lateral as well as along the anterior inner surface of the yolk-stalk, and the subsequent differentiation of the same from anterior to posterior into hepatic tissue, has occurred. Second, the lateral aspects of the U-shaped free border have approximated each other and fused progressively from before backward. As a result of this fusion, the ventral surface of the proton has been brought into existence and constantly increased by posterior extension. Third, the posterior recession of the yolk-stalk on a plane with the newly developed ventral surface of the proton, and the growth of the prehepaticus beneath this surface have proceeded (compare Figs. II, 12, and 13, ph). On account of these changes, the proton which in stage 1 could be said only to lie upon the prehepaticus, begins to lie partially within it.

The contours of the internal and external surfaces coincide in general, although there are promiscuous variations in the mural thickness, aside from the regular variations previously noted. There are certain small, sharply-defined projections on the external surface, which will be described under histogenesis.

A more matured condition of the proton in this stage differs slightly from the preceding proton in that the features of special interest in the foregoing specimen are more obvious in this one (Figs. 2, 2a, and 12). The most important new feature seen in this model is the anterior constriction. It is indicated by a constriction at the dorsal border of the anterior surface immediately beneath the intestine (ca). It is the beginning of the progressive separation of the proton from the intestine. By virtue of the constricting process and the extension of the ventral surface, the evaginated portion is deepened and enlarged. The enlargement has taken place partially at the expense of the lateral alar extensions, in so far as they have been incorporated into side walls of the evaginated increment. The more sacculated the proton becomes the deeper it is embedded in the septum transversum.

Stage 3 (Figs. 3, 3a, and 13). The ultimate extent to which the intestinal wall differentiates into hepatic tissue is nearly, if not wholly, determined at this stage. The remarkable recession of the yolk-stalk has been accompanied by an increase in the anteroposterior length of the ventral surface of the proton, by way of fusion, such as is described in the foregoing stage. Of great significance is the fact that the differentiation of the ordinary intestinal epithelium into hepatic structure, has not kept pace with the recessive migration of the yolk-stalk. Therefore, the free border of the proton is no longer existent. In its place is the line of union of the proton with the intestine lying posteriorly between the hepatic tissue and the yolk-stalk (i). Accordingly, the mouth of the evagination does not, as in the previous stage, open into the space where the lumina of the intestine and of the yolk-stalk conjoin, but into the lumen of the foregut proper.

On the ventral surface of the model, there are three depressions extending transversely across it. The most posterior one (dv*) indicates the locality where the foregut dips slightly into the yolkstalk. The middle one (cp) indicates the region where the ventroposterior limit of the proton passes into the ordinary epithelium of the foregut. The most anterior one (dv') is an incipient constriction between that part of the proton which develops all or most all of the glandular structures—pars hepatica of Brachet (P. hep.) —and the portion which is the rudiment of the gall-bladder and ventral pancreas structures—pars cystica of Brachet (P. cy.).

Thus, the pars cystica is here outwardly indicated for the first time as that convexity of the ventral protonic surface lying between the anterior and middle ventral depressions. In the previous stages, the form-conditions of its presence are not only lacking, but the tissue rudiment of it is wholly unformed or only partially existent ; since all or nearly all of the intestinal epithelium which can be recognized as part of the hepatic proton partakes of the characteristic structure of the pars hepatica. In view of the fact that the proton develops antero-posteriad and dorso-ventrad, and since the gall-bladder occupies the ventro-posterior part of the proton, it is clear that the pars hepatica is formed before the pars cystica. The wall of the pars cystica is somewhat thicker than that of the pars hepatica, and represents about one-third of the mural area (Figs. 3, 3a, and 13).

The mid-ventral depression (posterior constriction), is the counterpart of the anterior constriction already mentioned. The latter is more pronounced than in stage 2. The deepening of these separates the proton from the intestine more and more. They are connected by a more or less perfect longitudinal furrow on each side, running posteriad and finally ventrad. These furrows are the lateral aspects of the zone of constriction demarking the proton from the intestine.

Not only has the ventral wall of the proton extended posteriad, but that region of it posterior to the most anterior ventral depression, including as it does the ventral surface of the pars cystica, is now inclined slightly dorsad, antero-posteriorly. This dorsal inclination becomes greater and greater in subsequent development, until it is practically dorso-ventral in direction. Then this portion of the proton becomes part of the posterior wall (Figs. 4 and 4a, P. cy).

After cutting the proton by a plane in the manner that those of stage 2 are cut, thus dividing it into evaginated and alar-extension portions, the following conditions are very noticeable. First, it is clear that the evaginated portion has deepened. This is due to encroachment upon the lateral alar extensions as observed less conspicuously in the previous stage, to further extension of the ventral wall, and to increase in the anterior and posterior constrictions. Second, the mouth of the evagination is inclined more anteroposteriad, and opens more dorsad into the lumen of the foregut. Third, the alar extensions, instead of being almost posterior to the evaginated portion as in stage 1, are dorso-posteriad (d/). Since there is no free border, the line for the plane to pass through must be drawn to the most ventral point on the posterior border, instead of the most anterior point on the free border as in the previous stage.

The evagination has become trilobed by the anterior and the anterior ventral depressions. Since the former one is not constantly found in different specimens of this and older stages, the bilobing of the anterior wall is adventitious, but the bilobed condition of the ventral wall is a constant character of the development. In this stage the lobulation is not apparent on the lateral surfaces.

Stage 4 (Figs. 4 and 4a). By a process of lateral fusions and antero-posterior separations of the walls in the posterior constriction between the proton and intestine, this constriction has been deepened so greatly, that, on account of this deepening and possibly by the orientation of the posterior portion of the ventral wall into an approximate dorso-ventral direction, a posterior surface to the proton has been created.

The dorsal border of this new surface is on a level with the same border of the lateral and anterior walls. Consequently, no plane cutting the proton in accord with previously given directions will divide it into two parts. The alar extensions of previous stages have been incorporated completely into the evagination. Therefore, the proton is now an evagination from the ventral surface of the foregut into the septum transversum, and its cavity communicates dorsally by a slightly constricted neck, with the lumen of the foregut.

The variations in the contour of the proton and in its relative dimensions seem to become greater in these more advanced stages. In lateral aspect and in median sagittal section, there is considerable antithesis between the proton of embryo G under discussion and that of embryo D (Figs. 5 and 5a). The former is very deep and the depression between the pars hepatica and the pars cystica is slight.

In the latter this depression is very deep, and thereby makes the liver proton appear to be a quite double evagination. The proton of embryo G in cross-section is narrow, deep, regular, and U-shaped. Embryo P furnishes a proton which is extremely irregular on every side. A cross-section through the deepest portion of the pars hepatica of embryo D would reveal a shallow evagination with a lateral dimension exceeding the dorso-ventral measurement several times,—the reverse of the proportions found in embryo G.

The solution of the problem as to whether in embryo D there are really one or two diverticula may be approached from two standpoints.

Standpoint 1. Take dorso-ventral measurements in the median plane from the dorsal wall of the intestine, to the ventral surface of the intestine anterior to the proton (d?), to the same surface posterior to the proton (d°), and to the surface of the depression between the pars hepatica and pars cystica (d?). The last measurement is no greater than the first or second, and no point elsewhere on the depression is below the level of the point measured to. And since the intestinal caliber anterior and posterior to the proton is about equal, the space between the two diverticula may be considered to be in the level of the ventral surface of the intestine. Therefore, there are two separate diverticula.

Standpoint 2. Cut the proton by a plane as directed for demonstrating the evaginated portion in other models. At no point does the depression rise quite high enough to meet the plane. Therefore, the plane may be considered to coincide with the mouth of a single, deeply bilobed evagination.

The view that there are two diverticula appears to me the most obvious and satisfactory. In assuming this attitude, the objection to it that has been pointed out may be answered by referring to the fact that the dorsal wall of the intestine above this depression suffers down-curving, at least as great as the distance which the depression lacks of meeting the plane.

This is the only model which has shown two distinctly separate diverticula, and is the only one in which the intestinal wall above dips downward. The contour of the intestine at this place may have been straight normally, although not the slightest evidence was discovered to indicate the curved condition to be abnormal. The external appearance of the embryo before embedding was perfect.

The belief that there are two separate diverticula does not in the least dispose one to the conclusion that they were so primarily. They probably were not, because a simple exaggeration of the anterior ventral depression could have been the factor which made two separate diverticula out of a single primary one, in the manner similar to that by which the bilobing of other protons has been effected.

The rudiment of the gall-bladder which in the previous stage is very shallow and basin-like, and opens dorsad within the primary evagination of the proton, is, in the present stage, a somewhat deeper evagination of the ventral part of the posterior wall, and opens anteriad (gb).

In the posterior wall, between the gall-bladder and the intestine above, is a more or less conical, bilobed, solid outgrowth of tissue. This is the ventral pancreas (pv). It is a thickening of that portion of the pars cystica which goes to form the ductus choledochus.

Only one stage later than that just reviewed has been modelled (Fig. 6). In it the zone of constriction has closed in so as to leave a very small, narrow neck at the mouth of evagination (mn). The evagination is somewhat flask-shaped and deeply divided into four lobes, aside from that portion composing the rudiment of the ventral pancreas. One of these lobes extending posteriad and to the right is the gall-bladder. It is well rounded; its wall being thicker on an average than that of the pars hepatica. Its surface is smooth and sharply defined from the adjacent tissue of the prehepaticus. Of the other three, one is to the right (rt), one is to the left (J), inclining dorsad, and one proceeds ventrad (v). The left one is the smallest. They taper toward their distal end and, at their proximal extremity, spread out into the walls of the main cavity of the flask. Where the proton joins the intestine, the latter runs somewhat transversely from left to right (¢ér).

Relation of morphologic variations to blood sinuses

Idiosyncrasies in mural contour are accompanied by corresponding peculiarities in the disposition of adjacent sinuses.

In embryo D (Fig. 16) there is a large vessel lying immediately beneath the deep depression between the pars hepatica and pars cystica. On both sides of the deep, narrow, U-shaped wall of embryo G (Fig. 14) are observed very large sinus-like spaces.

The proton appears to have dipped ventrad in the narrow interval between the vessels.

In embryos X?, J, and K (Figs. 11, 12, and 13), the sinus venosus at its posterior end lies close to the anterior wall of the proton, in such a way that it coincides with the anterior (sinus) depression (ds) which bilobes the anterior surface. This depression is seen in the models of embryos J and K. Thus, the bilobing of the anterior surface seems to be due to the close approximation of the sinus which by active pressure, or its own resistance, makes an indentation.

In the very irregular wall of embryo P (Fig. 15), the deep depressions are filled, more or less, with large sinuses. From these observations it appears that the irregularities of growth are the results of obstructions to expansion, offered here and there by these sinuses.

General configuration of the external surface

In stage 1 (Embryo X"*) and in stage 2 (Embryos S and J), the surface, although sinuous by virtue of indentations and convolutions, is smooth, and well defined from the adjacent tissue of the septum transversum. The few exceptions to this are some minute papillary excrescences. They protrude slightly from the general surface. In stage 1 they are less in number and in magnitude than in the later stages (Fig. 15, p).

The papillae develop earliest and are largest on the anterior median surface. Posteriad over the lateral and ventral surface, they become smaller and fewer and finally disappear. In other words, the older the protonic wall, the more mature and numerous are the papillae. Consequently, the more advanced the stage of development, the more completely and extensively is the posterior and younger region of the proton involved in the extrusion of papillae.

In stage 3, where for the first time there is a definite pars cystica, it is necessary to state that this part of the proton always possesses a smooth, well-defined wall, excepting perhaps at its most anterior portion. The pars hepatica, however, especially anteriorly, is studded with numerous papillae, some of which have grown out into short rods. These rods are usually separated by vascular spaces. It often happens at this stage that several of them near the median anterior region of the proton, where they are more mature, are not separated but are closely approximated, forming a more or less compact cell mass (Figs. 13 and 19, rc). This is the only structure apparently homologous to the “kompakte Leberanlage.” It is minutely discussed under histogenesis.

In stage 4 (Embryos G and D), the papillae and rods have still further increased in number, magnitude, and range. Most of the simple short rods of stage 3 have elongated and branched. These branches, in most places, have united end to end, and form a network (Figs. 14 and 16). This configuration of the wall occupies at least the anterior half of the proton. It becomes less complex posteriorly and the rod disappears altogether at a limit indicated (Fig. 4, ri). Posterior to this limit the surface is smooth or slightly papillated. But within this smooth wall, as far posterior as the dotted line (p/), the cell arrangement peculiar to potential evaginations is discernible. Since all this structural variation which determines hepatic tissue, covers about four-fifths of the wall, that amount is gland-formative and represents wholly or almost entirely the pars hepatica portion of the proton. These potential structures are discussed under histogenesis.

In later stages, this net-work of rods becomes larger and more complex, and finally arranged into the characteristic glandular structure. In the case of embryo E, the rods arise from all parts of the proton excepting from the gall-bladder, the appended ventral pancreas, and the narrow neck leading to the intestine.

Comparison of results with those of other authors on mammalia

His (81) says that the “ Leberanlage” first appears as a longitudinal strip on the ventral side of the foregut. Peterson (99) also demonstrated this in the pig. This research confirms it likewise.

“ Kolliker (79) hatte bei dem Kaninchen zwei Lebersprossen beschrieben, deren erster am zehnten Tage auftritt, wahrend der zweite erst am elften Tage der Schwangerschaft erscheint. Sie stehen zu einander in einem ungefahren rechten Winkel.” [Quoted from Brachet (96).]

Kolliker’s two “Lebergange” are given as right and left. Stage 3 furnishes two “ Lebersprossen” in the relation of right angle to each other, but one is anterior and projects forward, the other is posterior and projects downward. The anterior one is the pars hepatica. The posterior one is the pars cystica (Fig. 3a). The model of embryo K, which is taken as the type of stage 3, is evidently trilobed instead of bilobed. However, since the anterior (sinus) depression, which divides the pars hepatica into two parts, is adventitious, and since the anterior ventral depression, which divides the proton into the pars hepatica and pars cystica, is a constant element in the morphology, the bilobed condition is the characteristic one.

“ Felix (92) dagegen will die zwei Leberknospen, aus denen diese Driise hervorgehen soll, bei menschlichen Embryonen gefunden haben. Indessen sind diese beiden Knospen weit davon entfernt, denen zu gleichen, welche Kolliker bei dem Kaninchen gesehen hat. Denn er giebt an, dass der eine kranial, der andere kaudal gelegen sei. Der letztere endlich ist ganz und gar rudimentar und kann in spateren Stadien kaum wieder erkannt werden.” [Quoted from Brachet (96).]

This research does not bear out the results of Felix, because no atrophic “ Leberknospe ” is present. On the other hand, both the pars hepatica and pars cystica undergo progressive metamorphosis.

“His (81) hatte die zwei von Kélliker beschriebenen Divertikel weder beim Kaninchen, noch beim Menschen wiedergefunden. Stets sah er jedoch nur einen einzigen, der von der ventralen Wand des Darmrohres ausging und der zum grossen Teil mit dem Septum transversum zusammenhing; durch Zellwucherung seiner Wande entstand aus ihm eine dichte, kompakte Zellmasse: die kompakte Leberanlage.

“Die Gallenblase tritt spater auf in Gestalt eines sekundaren Divertikels des Leberausfithrungsganges.” [Quoted from Brachet (96).]

The proton of stage I is more primitive than this, because no diverticulum appears in the former. Otherwise the proton of stage I answers in a general way to this description. The evaginated portion of the proton in stages 2 and 3, and the entire proton of stage 4, correspond more or less to His’ description. Although the gallbladder appears subsequent to the beginning of the hepatic portion of the proton, it is, nevertheless, evident in stage 3, wherein there is as yet no well-defined “Ausfiihrungsgang.” Moreover, in stage 4 and in the latest stage modelled, the gall-bladder is below the “Ausfiihrungsgang.” Concerning the “kompakte Leberanlage” of His, which is confirmed by Brachet and by Hammar, a discussion is found under histogenesis.

Hammar (97) after stating the proton in some other classes of vertebrata to be a fold of the ventral gut wall, turns to mammalia and describes it in the rabbit, in the following quotations :

“Auch bei den Saugetieren wird eine stufenahnliche, sich zwischen die Venenschenkel des Herzens hervorschiebende Leberfalte beim Darmverschlusse gebildet (Fig. 4).”

This statement indicates that the proton in the pig and rabbit does not differ materially in position and derivation.

“Wahrend diese letztere sich zum trabecularen Leberparenchym herausbildet, wird die Leberfalte allmahlich durch eine caudalwarts fortschreitende Abschniirung (Fig. 5) als ein selbstandiger Gang vom Darmrohre abgetrennt.”

In connection with this last quotation, it should be noted that he observes the anterior constriction, proceeding “caudalwarts,” to be the only factor potent in the separation of the proton from the intestine. And, according to his model (Fig. 5), this seems to be true, since no posterior counterpart to it, such as the posterior constriction in the proton of the pig, is appreciable. The fact that the anterior constriction between the proton and intestine is slight in the pig, and that in the rabbit it extends posteriad as far as the posterior border of the ventral surface, makes a vast difference in the appearance of the two protons. In the rabbit the proton, as presented by Hammar’s Fig. 4 and Fig. 5, is entirely a deep evagination projecting anteriad. At its posterior aspect alone it opens into the foregut where that receives the yolk-stalk. The shallow proton of the pig embryo in those stages corresponding to the aforementioned figures of Hammar, presents both posterior and dorsal aspects open, and it is an evagination only in part.

If in stage 3 (Fig. 3) the anterior constriction was deepened antero-posteriorly, until it furnished a dorsal surface about equal in length to the ventral surface of the proton, it would give an evagination projecting anteriad beneath the intestine and opening into it posteriorly. The dotted line (ha) indicates the imagined constriction. Such a condition is what Hammar gives for the rabbit in his Fig. 4 and Fig. 5.

“Unmittelbar caudalwarts von der compacten Leberanlage sprosst ein anfangs ganz kurzer Zapfen von der ventralen Wand dieses Ganges hervor (Fig. 6).”

Hammar’s model illustrated by his Fig. 6, the gall-bladder rudiment of which he describes in the above quotation (“ein anfangs ganz kurzer Zapfen”), resembles very closely the model of the proton in embryo G, representing stage 4. The two models differ mainly in the shape of their gall-bladder rudiments. In the rabbit model under discussion, it is a long, narrow projection. Between Hammar’s Fig. 5 and Fig. 6, a constriction at the posterior extremity of the ventral surface of the proton has evidently occurred, since in Fig. 6 the proton projects ventrad instead of anteriad and opens dorsad instead of caudad as in Fig. 5. In other words, the mouth of the evagination has been shifted and a posterior wall created, undoubtedly by the initiation and deepening of the posterior constriction. These phenomena transpired in the proton of the pig during stage 3, and resulted in the form-condition of stage 4. The metamorphosis in both instances is similar, and it is not unlikely that the factors producing it in both are the same.

Brachet (96) :

“ Auch bei dem Kaninchen wird die Leber durch eine breite longitudinale Ausbuchtung (renflement) der ventralen Darmwand angelegt, welche sich tiber diese vom Sinus venosus bis zum Nabel hinzieht. In den vorderen und mittleren Partien dieser Ausbuchtung, oder dieser Vorstiilpung der ventralen Darmseite fangt das Epithel zu wachsen an, bildet einen epithelialen Zellhaufen, welcher in Verbindung mit dem Septum transversum tritt und zur ‘kompakten Leberanlage’ von His wird.”

The above elucidation of the derivation and relation of the proton to the septum transversum answers to the condition found in the pig. As to the posterior boundary, it answers to the two early stages, but not to later ones, because in them the ordinary intestine intervenes between the proton and the “ Nabel.” As to shape, stage 1 in the pig proton is more primitive, since as yet there is no “ Ausbuchtung ” or “Vorstiilpung.” Concerning the “epithelialen Zellhaufen,” a discussion is made under histogenesis, where the “kompakte Leberanlage” is taken up.

“An dem hintersten oder kaudalsten Teile der Wand jener Ausbuchtung (renflement) findet niemals eine derartige Zellwucherung statt. Er bleibt immer glatt und wohl von seiner Umgebung abgegrenzt. Durch Abschnirung und Eingenwachstum bildet sich spater die Gallenblase daraus.”

“In der That kann man also auch hier bei der primitiven Leberanlage eine ‘Pars hepatica’ und eine ‘Pars cystica’ unterscheiden. . .”

“Eine doppelte Abschniirung, die in kranio-kaudaler wie in kaudokranialer Richtung erfolgt, trennt sowohl die ‘ Pars hepatica’ wie die ‘Pars cystica’ von der ventralen Wand des Darmrohres und lasst sie nur noch durch einen breiten Stiel damit verbunden der dann seinerseits spater zum Ductus choledochus wird.”

All points considered in the three paragraphs just quoted are true for the proton of the pig.

No author speaks of that portion of the proton which, in certain stages, extends beyond the evaginated portion, and which is designated in this paper as the lateral alar extension.

Notes on the origin of the ventral pancreas

The ventral pancreas is located on the posterior portion of the pars cystica. In case the gall-bladder portion of the pars cystica has been differentiated from the ductus-choledochus portion, the ventral pancreas appears on the latter, thus being situated between the gall-bladder and the intestine.

There are three form-conditions of the ventral pancreas illustrated in the plates. The most primitive is that in the model of embryo D (Fig. 5). Herein it is in the shape of two elongated solid outgrowths projecting caudad and slightly ventrad from the posterior lateral aspect of the pars cystica, considerably to the right of the median line (pv). One is several times smaller than the other and situated antero-ventrad to it. The latter is club-shaped and about three to four times longer than the smaller one.

The second morphologic feature of interest is observed in the model of embryo G (Fig. 4). Both embryo D and embryo G belong to stage 4 in the development of the hepatic proton, but embryo G is decidedly the more mature as respects the liver proton and probably also as regards the ventral pancreas. It subsists in a solid, single, and somewhat conical extrusion of cells placed in the median line, dorsal to the gall-bladder and ventral to the intestine. Although the ventral pancreas in this case is single, it is not simple, because a laterally bilobed condition is present. Moreover, these two lobes stand in the same relation that obtains between the two separate projections of embryo D; that is, the right lobe arises more anteriorly and is slightly ventral to the left, which is closely limited to the posterior aspect of the proton.

The most mature form of the ventral pancreas, furnished by embryo E, the oldest one studied, is that of a long narrow solid outgrowth of cells which is not bilobed. At the distal end it is inclined slightly upward and apparently toward the right side of the transverse intestine above it.

If the various forms of the ventral pancreas in this small series represent successive changes in its growth, it has originated by two solid diverticula at first situated posteriorly on the right side of the pars cystica. These later have occupied the posterior surface in the median line by shifting posteriad, and have fused into one outgrowth by approximation. Furthermore, this fused pancreatic proton has increased in length posteriad and dorsad toward the right aspect of the intestine. Wlassow (95) discovered in the pig merely a single outbudding from which the ventral pancreas was derived.


The simple, smooth wall

In stages 1 and 2, as above defined, the external surface of the protonic wall is nearly smooth. This smooth wall includes a varying portion of the proton in all stages described in this paper. Its histological structure provides the basis for the more highly specialized formations that constitute the liver.

In stage 1, the intestinal epithelium is composed of a single layer of short columnar cells. Where the intestine becomes continuous with the hepatic proton, an immediate alteration in the cell-arrangement and in the thickness of the wall is evident.

Not only has the wall of the proton differentiated from the intestinal wall in (1) cell-arrangement, and in (2) thickness, but also in (3) plasma-staining properties. Where the protonic wall has been developing the glandular structure, Ehrlich’s acid haematoxylin, picric-acid, and other plasm stains give a deeper coloration to the plasmatic portion of the liver cells than to any other tissue contiguous. Nuclear stains also take avidiously. When surrounding tissues are well stained, the liver is liable to be over-stained. Stages 1 and 2 do not exhibit this peculiarity in plasma-staining as much as those more advanced, nor does the posterior portion of the proton indicate it so markedly as the anterior, because the more differentiated the tissue is, the deeper it stains. The pars cystica shows it little, if any.

Stage 1 (Fig. 7). The free yolk-stalk border of the proton is composed of a single layer of cuboidal or polyhedral cells (cc). Next to the margin of cuboidal cells is a region of short columnar or wedge-shaped cells (csw). Then, more distal from the free border where mural thickness increases, they are longer and more closely packed. Where the wall gains its average diameter, they are slender wedge-shaped cells, generally spanning from surface to surface (clw).

At intervals, polyhedral cells with spherical nuclei are found adjacent to the inner surface. They are often observed in process of mitosis. In fact, most of the karyokinesis in the proton is near this surface and in these cells (cm).

The nuclei of the marginal cuboidal cells are generally spherical ; of the columnar and wedge-shaped cells the nuclei are generally oblong or ovate; and the longer the cells, the longer their nuclei are.

Since so many of the long cells, even in the thickest part of the wall, span its entire width, one can hardly demonstrate that more than a single cell-layer exists in the proton wall. But wherever the wall is composed of columnar or wedge-shaped cells, there are at least two regions corresponding to the mural surfaces and characterized by peculiar cell-structure and arrangement. The regions are (1) the inner, where the inner extremities of the long wedge-shaped cells and the polyhedral cells with spherical nuclei are found; and (2) the outer, made up of the outer, nucleated extremities of the long wedge-shaped cells. Of these regions, the former occupies about one-fourth the diameter of the protonic wall, and karyokenesis is more common in it than in the latter, which constitutes the remaining three-fourths of the diameter.

The nuclei of the long cells are in three more or less definite series or rows, where the wall is of ordinary thickness, and in two rows in the tapering portion of the wall composed of short, wedge-shaped cells. As regards the three rows of nuclei in the former region, those of the inner row are approximately ovate. Their narrower end points outward and is often located between the inner extremities of two nuclei of the middle row (Figs. 7, 8, and 17, nt).

The nuclei of the outer region are of similar shape. Their inner extremity is the narrower and lies between the outer ends of nuclei of the middle region (no). The nuclei of the middle region are oval or ovate, tapering at either or both ends. Thus the nuclei of the long cells are observed to dove-tail with each other. As regards the two rows of nuclei in the latter region of the wall, they are more rotund and dove-tail with one another near the middle of the mural diameter. Aside from this general tendency toward serial variations in form and arrangement, some spherical or oval nuclei are evident everywhere, especially in the inner and outer series.

Stage 2 (Figs. 8 and 17). The principal differences in the histology of stage 2 and of stage 1 are observed in (1) a much more rapid transition from the thin yolk-stalk border to the normal thickness, and in (2) the greater thickness of the wall, involving an increase in the length and number of cells and nuclei.

Stages 3 and 4. The histology of the wall in these subsequent stages varies only in minor details from that in stage 2. Of course, the tapering yolk-stalk border is absent. The mural thickness may or may not be greater. If it is considerable, there may be more than three rows of nuclei evident. The typical arrangement is less conspicuous because of the increasing multiplicity of secondary changes incident to the developing glandular structures.

Development of the glandular structure

Potential evagination. The incipiency of gland development is very evident, even in stage 1. It is indicated by a peculiarity of arrangement among the nuclei of the long wedge-shaped cells. At the indicated place on the figure (Fig. 7, ep), six nuclei form a little arch, its base resting on the inner surface and its vault reaching to the outer surface of the wall. The cup-shaped cavity of the arch is filled with the cytoplasmic inner extremities of the cells possessing the nuclei which compose it. These cells and their nuclei are perpendicular to the surfaces. The cells themselves are not peculiar, excepting as regards the collective arrangement of their nuclei. Furthermore, this structure is entirely within the wall at its ordinary thickness. Nothing can be observed of it superficially. It is a potential evagination. Probably even a much earlier condition of this is found among the layer of short, columnar cells, in the tapering yolk-stalk portion of the wall (Fig. 7, op). Here four or five spheroidal and oval nuclei form a very low arch.

It seems that the conditions for the development of the potential evagination are found in (1) the chaotic distribution of nuclei in the thin margin of the wall, two contiguous nuclei seldom being at exactly the same level; (2) in the variable size of nuclei; and (3) in the difference of their surface contour. With these three conditions present, it is easy to see that where the cells and nuclei begin to crowd each other closely, as at (ep), not only do the cells elongate, but also the nuclei arrange themselves serially. The serial accommodation is probably accomplished by the nuclei moving toward the inner or the outer surface, wherever pressure directs them. The formation of arches is one of the possible and apparent results of pressure on the nuclei so conditioned.

But these factors do not explain why the arches always take the form of evaginations, and seem never to construct invaginations. Perhaps another factor is physiological, in that the source of nutriment is from the outer surface where the blood-spaces of the septum transversum bathe the proton with nutrient fluid (Figs. 14 and 15, sn). That this conjecture may be of importance is supported by the fact that, in general, nuclei are in that part of the cell wherein physiological activity is greatest, and by the fact that the nuclei in the proton tend to be and are in large part near the outer extremity of their cells. The mechanical conditions of pressure on each side of the wall undoubtedly differ. On the lumen surface there is simply free fluid which presumably exerts an equal hydrostatic pressure at all points. On the other side there is not only fluid pressure, but also a framework of fixed tissue which furnishes some support at numerous points and at other places provides very little resisting power to counter pressure. Yet it seems that other factors are involved, because the pars cystica, developing under apparently similar conditions, does not form glandular structures.

The more advanced potential evaginations, such as stage 2 furnishes, are deeper, and more cells take part in their make-up (Figs. 8 and 17, ep). The cells of every advanced evagination, with the exception of those in the central axis of each, do not extend perpendicularly to the mural surfaces, but are disposed obliquely to them. They are oblique to the central axis, so that their outer ends are more distal to it than are their inner ends which are directed toward it, and aid in filling with cytoplasm the cup-shaped cavity of the arch. The more mature the potential evaginations are, the more pronounced as a rule, is this obliquity of the peripheral cells and their nuclei. Where the axis of the evagination meets the inner surface of the proton, small, sharply-defined indentations sometimes occur.

Papilla-formation. Papillae, varying in form, project from the external surface of the pars hepatica, and perhaps also from contiguous areas of the pars cystica. Even in stage 1 a few very low rudimentary papillae are noticeable. These papillae are simply a higher development of the glandular structure. What have been observed to be potential evaginations are the prototypes of exuberant evaginations, the papillae. That is, the papillae or exuberant evaginations are the second morphologic aspect of the gland-formative process. Histologically, three modifications of the papillae are easily recognizable. Each represents a certain degree of maturity.

The least mature papillae (Fig. 7, p) differ from the potential evaginations only by virtue of their columnar or wedge-shaped cells being longer than the longest cells of the wall at its ordinary thickness. They exceed them in length by the extent that the papillae project from the outer mural surface.

The more mature papillae possess longer cells composing the core about their central axis. Often some of the cells are spatulate ; their long, slender inner extremities reaching across the wall to its inner surface (Fig. 9, p?), converge more uniformly and sharply toward the central axis than in younger papillae. The most peripheral cells are long, wedge-shaped, or slightly spatulate. To reach the outer surface, they bend obliquely away from the central axis at that extremity, and are no longer straight (Fig. 9, p?, clw).

The most mature papillae are longer than others (Fig. 18). The cells of the axial core are extremely long and spatulate. They are approximately straight and parallel with the papillary axis. Their long, slender inner ends often taper apparently to hair-like processes, and it is doubtful if those most centrally situated reach as far as the inner surface. In most sections some of them do not appear to. The change of cellular outline from wedge-shaped to spatulate has invaded the peripheral portion of the papillae from the axial core outward, and all cells, with perhaps the exception of a few most peripheral, are spatulate. The expanded outer extremities of the peripheral cells bend to a much greater degree than in the less mature papillae, and may be almost at right angles to their slender inner ends. There is a tendency for this bend to be sufficient for the cells to meet the curving papilla-surface at right angles.

The shape of the nucleus does not change appreciably when a cell develops from the wedge-shaped to the spatulate form. But in the expanded outer end of the spatulate cells which form the apices of the most mature papillae, the nuclei are somewhat spherical. All cells which, in later stages of normal development, are superposed on these apical spatulate cells, are polyhedral and possess spherical nuclei. Such polyhedral cells with spherical nuclei, are characteristic of the rods constituting the subsequent glandular structure of the liver. Their presence marks the end of the papilla form of evagination and the beginning of the rod-formation (Fig. 18). Perhaps the first few polyhedral cells are modified spatulate cells which have assumed this shape by a progressive shortening of their attenuated extremities.

Rod-formation. The ordinary growth of the rods, so far as traced, is characterized by cell-proliferation, and by the arrangement of these cells according to a certain type; by the extension of the rods into the septum transversum; by their branching ; and by the resolution of these branches into a network of rods.

The size of the rods at their base depends very largely on the size of their antecedent potential evaginations and papillae. If a rod springs from a very wide papilla (Fig. 15, pw), the rod is broad. A cross-section of such a one shows a circloid area composed of twenty or more polyhedral, cuboidal, or short columnar cells, arranged in a single row about a common center. At the center a small lumen is often apparent. The nuclei of the polyhedral cells are spherical; of the columnar cells, slightly oval. They always tend to be distributed at the peripheral side of the cells. Ifa rod springs from a very slender papilla (Fig. 15, ps), it is correspondingly slender and has much the same structure in section that the broad rod exhibits.

Obstruction to growth modifies the form of the rods and of their cells. When a simple rod grows into the septum transversum between blood-vessels, where there is room for its unthwarted extension, it develops typically a.straight cylinder with rounded distal extremity (Fig. 15, 7). When its distal end rests against a blood-vessel (Fig. 15, 7), or between vessels offering obstruction to extension, this extremity is apt to be excessively thick, and the cells composing it are usually columnar instead of polyhedral. The longitudinal median section of a rod obstructed on one side by a vascular space is constituted on that side of well-developed columnar cells, whereas the opposite side, which suffers less obstruction, is composed of nearly cuboidal or polyhedral cells (Fig. 20).

After the simple rods have grown outward a short distance, they bifurcate. These branches also subdivide. By progressive extension and subdivision, each original simple rod grows into a dendritic system, of which it is the trunk.

In this tree-like system, the more distal the branches, the smaller they are. Some are merely strings of single cells placed side by side (Fig. 16, 7’). Thus, branches may contain in a cross-section from a single cell to twenty or more. Most branches show from five to eight cells (Fig. 16, rs), about a very small central lumen. The central lumen can be traced very nearly to the internal surface of the protonic wall, in some instances (Fig. 20). The trunks of these dendritic systems and the more immediate branches of them, are more apt to contain columnar cells than are other branches.

Among the columnar cells of the large rods are often found potential evaginations and papilla-formations (Fig. 16, re). These phenomena incident to rod-outgrowths are common in certain parts of rods that have thickened by virtue of obstruction to extension.

The dendritic arrangement is never isolated and perfect. Before many bifurcations have occurred, the rods fuse end to end with those of the same and of contiguous systems, forming a net-work. In stage 4 the net-work is the most conspicuous portion of the developing liver (Fig. 14).

Relation of vascular spaces to glandular development.—The protonic wall is almost always separated from the blood-spaces by an interval filled with mesenchyme. Sometimes a vessel touches the proton, but never does one penetrate the wall in any degree (Figs. 15, I9, and 20). The papillae and simple original rods sustain a similar relation to the sinuses (Figs. 14 and 16).

When the network of rods is formed, its meshes enclose a network of blood-spaces, of which the larger near the protonic wall come in close contact with the rods at many points (Fig. 14, sn). In the peripheral parts of the septum transversum the spaces are small, capillary-like, and more numerous. Between them the sepa-rate distal branches of the rods lie. Here also the vessels and rods are separated by mesenchyme (Fig. 14, sa). As the development of the glandular net-work progresses, the vascular spaces near the proton seem to increase in caliber and come into closer relation with the rods (Fig. 14, sn).

The bifurcation of a rod seems always to be conditioned by the close proximity of a vascular space to its distal end (Figs. 14 and 16, bf). The two branches generally extend beyond the vascular space in V shape. Division generally occurs before the rod is in direct. contact with the vascular space. When division occurs in proximity to a large vascular space such as the sinus venosus, the two resulting branches spread out at approximately right angles to the parentstem.

Other authors on histogenesis, and comparisons

The most interesting deviation of the results of this research from those of other authors on mammalia devolves about the relationship. of the vascular system in the septum transversum to the trabeculation of the glandular structures derived from the primitive protonic wall. A second important difference rests in the phenomena described concerning the method and direct results of the gland-formative proliferation. As to the method of the gland-formative proliferation, no details concerning the collective variations of form and arrangement peculiar to cells and their nuclei in the potential evaginations and in the papillae, have been described.

In regard to the direct result of proliferation from the proton, His describes the formation of a “kompakte Leberanlage” which is later formed into a net-work. Brachet confirms this statement by the terms “epithelialen Zellhaufen” and “kompakte Masse der Leberzellen” (vide extracts under ‘‘ Morphogenesis”). Hammar also gives expression to the same idea.

But no “kompakte Leberanlage” has been evident in the embryonic pig liver as here described. The rods of cells are morphologically distinct from their incipiency and, as a rule, remain separate. Ifa “kompakte Leberanlage” is evident on the wall of the proton, it is due to secondary fusion.

The relationship of the vascular system to the trabeculation of the gland-formative cells, as expressed by Shore (91) and by Brachet (96), is that blood-vessels penetrate the “kompakte Leberanlage” and break it up into a net-work of rods. The following quotation from Brachet (96) illustrates the point in question:

“In der grossen Mehrzahl der Falle entwickelt sich diese Netz durch ein Eindringen von Kollateralen, die den Gefassen der Nachbarschaft und zwar hauptsachlich den Venae omphalo-mesentericae entspringen, in the kompakte Masse der Leberzellen, die durch Proliferation aus der primitiven Leberanlage entstanden ist.”

According to the results of this research, however, the net-work of rods in the embryonic pig is formed independently of the active intervention of vascular spaces. The rods springing from the protonic wall grow into the septum transversum apart from the direct contact of vascular spaces. Many times they grow out where there are no vascular spaces anywhere near. The rods extend between the vascular spaces already present in the septum, and thus are kept separate from one another. Their individuality is retained typically, except when some of their advancing extremities meet and fuse. The entrance of vascular spaces into the hepatic tissue plays no active part in trabeculation of the gland, because they never penetrate into the proton or into the individual rods derived therefrom. Furthermore, the organization of the glandular elements is seen within the original wall, before any external manifestations of them are visible.

The vascular spaces limit and determine the possible direction of rod growth. They are also passively concerned in making the network, in that they facilitate subdivision by offering obstruction at the free ends of rods, thus making it convenient for them to branch in order to extend themselves.

In short, the hepatic tissue, instead of being grown into by the vessels, grows out and extends among and around them, although by virtue of increases in caliber, the vascular spaces actively change the location of rods.

Fusion of rods: Collateral growth: Disorganization The importance of the vascular spaces in keeping the rods separate is very obvious when it is noted how prone they are to fuse into a more or less homogeneous mass, where they run together in avascular areas (Fig. 14, rc).

That which, to some extent, resembles the “kompakte Leberanlage” of His is found in some embryos. It is best demonstrated in about stage 3 on the anterior wall of the proton, immediately posterior to the sinus venosus (Fig. 19). It is produced by the collateral outgrowth of a number of closely approximated rods into an almost avascular space. Since the region is practically avascular, and the rods contiguous, there arises a mass of tissue which produces a considerable thickening of the wall. But it is by no means a heterogeneous mass. It is a collection of contiguous rods. Their close approximation encourages fusion and more or less disorganization. In the figure cited, vascular spaces are apparently penetrating this collection. They are always between individuals of the collection. Therefore, they do not convert the outgrowth into rods, since the latter are already complete organizations, as can be observed by tracing each to its fundamental, histological arrangement within the protonic wall. The vessels simply separate the individuals from each other. Some of the evagination-formations at the bases of the rods are not illustrated as clearly in the figure given as in adjoining sections of the series.

Problems in trabeculation

There are some especially intricate problems in regard to the relation of the vascular system to the hepatic structures. Some of these problems could not be explained by direct demonstration. For instance, when a vessel is entirely surrounded by hepatic tissue it is often impossible to get a clew that will determine whether the vessel has grown into the hepatic structure, or has been surrounded by it. But, in certain cases, at a little distance from the circumference of the vessel, the site of the bifurcation of a rod has been seen; the two branches of the rod constituting the tissue which envelops the vessel. A very interesting example of a similar condition is conspicuous in cases (Fig. 10, sw), wherein a vessel at the outer border of the protonic wall is completely enveloped in a dense mass of hepatic tissue. That this vessel lies between two rods which were originally separated is demonstrated by the fact that in the wall on either side of the vessel are found the characteristic evagination-structures from which rods have sprung. The evagination to the right of the vessel discussed is not very evident in the figure, but is plain in an adjoining section of the series.

Whenever a rod becomes surrounded by a vascular space, it is impossible to decide whether the rod has pushed its way in, or whether the vascular space has expanded down over the end and sides of it (Fig. 15, r).

In case a vessel appears within a disorganized mass of rods, it is absolutely impossible to demonstrate what relation it has sustained to them.

Absence of the vaso-formative cells of Van der Stricht

Two forms of cells are described in the embryonic liver by Toldt and Zuckerkandl (75), and by Van der Stricht. One kind is the polyhedral cell with granular protoplasm. The other kind is a round cell with clear cytoplasm. The following quotation from Brachet (96) describes the two forms of which the round, clear type is said to be vaso-formative and the source of an intra-trabecular network of blood-vessels.

“Was nun den histologischen Aufbau der Lebertrabekel anlangt, so bestehen sie nach Toldt und Zuckerkandl aus zwei Zellarten. Die einen sind die eigentlichen Leberzellen von kubischer oder polyédrischer Gestalt, mit granuliertem Protoplasma und grossem Kerne; die anderen sind klein, rund und besitzen kein gek6rntes Protoplasma.

“Toldt und Zuckerkand! hatten diese letztere Zellform hauptsachlich im vierten Monat ausserordentlich reichlich angetroffen. . .

“Van der Stricht und Kostanecki haben jedoch geltend gemacht, dass die runden, hellen Zellen Toldts und Zuckerkandls nichts anders als Erythroblasten sind, welche die Maschen des intratrabekularen Gefassnetzes behaupten.”

It was impossible to find any small, round, clear cells in the stages of development which were studied, with the exception of erythroblasts in the sinuses and capillaries.

The gaill-bladder wall The gall-bladder wall in the stages discussed partakes of a histological arrangement similar to that described under the simple smooth wall. It is relatively thicker than that portion of the proton constituting the pars hepatica, and the columnar cells are therefore longer.

List of Embryos Cited in the Text

Corresponding Embryo Protovertebrae Embryo of Keibel’s Chart

Age x 19 8 17 days. Ss 21 9 16% “ J 21-22 10 16-17. “ P 26-27 10-11 16% “* K 27-(28) II 64% “ F 28 11-12 16% “ D 30-31 12 yy * G 32 12 7%, E 37 14 20 “


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Braus, HERMAN. 96. Untersuchungen zur verg!eichenden Histologie der Leber der Wirbelthiere. Habilitationsschrift mediz. Fakult. Jena.

Brun, A. von. 94. Leber und deren Entwickelung. Anatomische Hefte, Bd. IV.

Foster AND BALFOUR. 93. Elements of Embryology.

FELIx, WALTER. 92. Zur Leber und Pankreas-Entwickelung. Arch. fiir Anat. u. Entwick.

Hamoag, J. Aue. 97. Ueber einige Hauptziige der ersten embryonalen Leberentwickelung. Anat. Anzeiger, Bd. XIII. 98. Zur Kenntniss der Leberentwicklung bei Amphioxus. Anatomischer Anzeiger, Bd. XIV.

Hester, J. C. 99. Elements of Human Embryology.

His, WILLIAM. 81. Zur Embryologie der Satigetiere. His’ Archiv. (Quoted from C. S. Minot’s Human Embryology.)

KEreL, F. 97. Normentafeln zur Entwickelungsgeschichte der Wirbelthiere,

I. KostTaNECKI. 92. Die embryonale Leber in ihrer Beziehung zur Blutbildung, Anatomische Hefte, Bd. I. (Consulted in Brachet’s Resume, ’96.)

Kolliker, A. 79. Entwickelungsgeschichte des Menschen und der hodheren Tiere. Zweite Auflage. (Consulted in Brachet’s Resume, ’96.)

Minor, C. S. 97. Human Embryology. 98. On the Veins of the Wolffian body in the Pig. Proc. Bost. Soc. Nat. Hist., Vol. XXVIII, No. 10.

Peterson, O. A. 99. The Early Development of the Liver in the Pig. Thesis, Library of the University of Nebraska. (Unpublished.)

SHore, T. W. 91. Notes on the Origin of the Liver. Jour. of Anat. and Physiol.

ToLtpT AND ZUCKERKANDL. 75. Ueber die Form und Texturveranderungen der menschlichen Leber wahrend des Wachstums, Sitzungsber. d. Kaiserl. Akad. d. Wissensch. Wien. (Consulted in Brachet’s Resume, ’96.)

WLaAssow. 95. Zur Entwickelung des Pankreas beim Schwein. Morpholog. Arbeiten, herausg. von Schwalbe, Bd. IV. ‘

Explanation of Plates

All drawings of sections were made with a camera lucida. The finest details were determined by a Zeiss microscope.


bd Dorsal border. " Neck of proton. bf Bifurcation. ni Nucleus of inner region. bp Posterior border. nm Nucleus of middle region. bys Yolk-stalk border. no Nucleus of outer region. ca Anterior constriction. p 1-2-3 Papilla. ce Cuboidal cells. pd Dorsal pancreas. cm Mitosis-cells. ph Prehepaticus. clw Long wedge-shaped cells. Phep Pars hepatica. csw Short wedge-shaped cells, P cy Pars cystica. cp Posterior constriction. pl Papilla limit. d 1-2-3 Diameters. ps Slender papilla. dl Lateral dimensions. pw Wide papilla. dvd _Dorso-ventral dimensions. pu Ventral pancreas. ds Anterior (sinus) depression. r Rod. dv1 Anterior ventral depression. re Collateral rods. dv Posterior ventral depression. re Rod-evagination. el Evagination-limit. rs Rod-section. ea Alar extension. rl Rod-limit. ep Potential evagination. rt Right. gb Gall-bladder. s Section. ha Dotted line indicated in rabbit. sv Sinus venosus. ht Heart. sn Sinus-network. + Intestine. v Ventral. str Transverse intestine. vu Umbilical vein. 1 Left. vu Vitelline vein. ld Division-line. ys Yolk-stalk.

Plate I

Fig. 1. Lateral aspect of a model of the hepatic proton and adjoining intestine of embryo S, stage 2. About 50 X.

Fig. 1a. Median sagittal section of the same.

Fig. 1b. Transverse section of the same, taken at Fig. 1, s.

Fig. 2. Lateral aspect of a model of the hepatic proton and adjoining intestine of embryo J, stage 2. About 50 X.

Fig. 2a. Median sagittal section of the same.

Fig. 2. Lateral aspect of a model of the hepatic proton and adjoining intestine of embryo K, stage 3. About 65 X.

Fig. 3a. Median sagittal section of the same.

Fig. 4. Lateral aspect of a model of the hepatic proton and adjoining intestine of embryo G, stage 4. About 65 X.

Fig. 4a. Median sagittal section of the same.

Plate IV

Fig. 5. Lateral aspect of a model of the hepatic proton and adjoining intestine of embryo D, stage 4. About 75 X.

Fig. 5a. Median sagittal section of the same.

Fig. 6. Right anterior aspect of the model of the proton of embryo E. About 35 X.

Fig. 7. Median sagittal section of embryo X*, through the central half of the proton, exhibiting histogenesis in stage 1. 400 X.

Fig. 8. Transverse section through the ventral portion of the left alar extension of the proton in embryo S, showing histogenesis in stage 2. 400 X. (The position of it is represented by Figs. 1 and 10, s.)

Fig. 9. A transverse section of a fold in the protonic wall of embryo P, presenting cell-arrangement and incipient evaginations, 500 X.

Fig. 10. A portion of a median sagittal section of the proton of embryo K. 400 X.

Plate V

Fig. 11. Median sagittal section of embryo X’, stage 1. 20 X.

Fig. 12. Median sagittal section of embryo J, stage 2. 20 X.

Fig. 13. Median sagittal section of embryo K, stage 3. 20.

Fig. 14. Transverse section through the protonic area of embryo G, presenting stage 4. 40 X.

Fig. 15. Transverse section of embryo P through its protonic area, illustrating the histology and morphology in stage 3. 100 X.

Fig. 16. Sagittal section of embryo D through its proton, stage 4. 100 X.

Plate VI

Fig. 17. A section similar to Fig. 8, taken slightly more anteriorly. 400 X.

Fig. 18. A transverse section from the protonic wall of embryo P, showing cell-arrangements in the period of transition from a papilla to an incipient rod. 500 X.

Fig. 19. A section similar to that of Fig. 10, taken immediately caudad and ventral to the sinus venosus. (The nearest approach to a “Kompakte Leberanlage.”) 400 X.

Fig. 20. A transverse section of a portion of the protonic wall of embryo D, depicting a short rod, and exhibiting its relation as regards cellarrangement and direction of growth to the near lying vascular spaces. 600 X.

Cite this page: Hill, M.A. (2019, November 16) Embryology Paper - The early morphogenesis and histogenesis of the liver in Sus scrofa domesticus, including notes on the morphogenesis of the ventral pancreas. Retrieved from,_including_notes_on_the_morphogenesis_of_the_ventral_pancreas

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