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=The Role of the Auditory Sensory Epithelium in the Formation of the Stapedial Plate=

Franklin Pearce Reagan

Department of Comparative Anatomy, Princeton University

Ten Figures

==Introduction==

Certain structures which seem to have undergone transformation in the process of transition in vertebrate life from aquatic to terrestrial conditions have always been of great morphological interest. Structures of this sort are abundant in the pharyngeal region, which, especially in earlier times, furnished a most productive field of study. Such study was often concerned with the homologies among the nervous, muscular, vascular, skeletal and epithelial derivatives of this pharyngeal region.


Between the intermittent communications of the pharynx with the exterior there are developed mesenchymatous visceral arches in which chondrification takes place, forming the so-called 'visceral ribs;' these may ossify and retain their original position as components of the pharyngeal skeleton, or they may become greatly modified in the higher forms, acquiring a special function very unlike that of their more primitive homologues. In the lower vertebrates the pharyngeal ribs or components of the visceral skeleton tend to preserve their original resemblances to each other. Particularly striking here, also, are the great independence and the wide separation of the visceral skeleton from the skeleton of the central nervous system — the cranial skeleton. In some of the primitive elasmobranchs, for instance, the mere cutting of three ligaments may be sufficient for the complete separation of these two skeletal complexes (i.e., visceral and cranial). But even in forms as low as the holocephali, the visceral skeleton has become immovably articulated with the brain-case. Here the palatoquadrate is firmly fused with the cranial wall, and the upper end of the hyoid arch (hyomandibula) takes no part in this union; this is a distinct advance towards the differentiation of a definite quadrate.


The skeletal complex of the first visceral arch forms the cartilage of the jaws. The antero-dorsal cartilage is known as pterygoquadrate. The ventral element comprises {{Meckel's cartilage}}. In selachians these two are suspended from the skull by the hyomandibular cartilage, the latter having been derived from the dorsal portion of the second visceral arch. During the ontogeny of the higher vertebrates the pterygoquadrate and hyomandibular homologues become very closely associated with the developing cranial skeleton, either losing entirely their identities, or becoming greatly transformed. Certain it is that the jaw articulations of the lower forms are not homologous with those of higher ones.


The hyomandibular, or at least the dorsal portion of the second visceral cartilage, is believed by many to be represented by that columnar bone in the series of ear-ossicles which becomes the most intimately associated with the otic capsule. In amphibia, sauropsida, and monotreme-mammalia, this homologue has been called by various names such as 'columella,' 'columella auris,' and 'columella cranii.' The cartilaginous plate fitting into the fenestra ovalis has been designated in amphibia as the 'operculum.' In higher forms the cartilaginous plate occupying the fenestra ovalis is known as the stapedial plate.


The terms 'columella' and 'columella cranii' have been employed with a great deal of confusion, as, for instance in the writings of Gegenbaur and Schimkewitsch. Gegenbaur (Vergl. Anat. der Wirb., p. 374) interprets the columella of amphibia as follows:

In urodeles there is a ligamentous process stretching from the operculum to the cartilaginous quadrate. In the anura the operculum is continued as an elongate ossified staff, the columella, which is to be regarded as a part of the auditory apparatus. These are two skeletal units which have taken the place of the hyomandibulare.



He regards (p. 380) the columella of reptiles as a homologue of the upper end of the hyoid arch, but derives the operculum from the chondrocranium. On p. 386 he states:

To the labyrinth region belongs still another bone which springs up from the pterygoid to the parietal — the columella. It has a cartilaginous Grundlage (Leydig) which is laid down on a process of the chondrocranium (Gaupp) and which is also distinguishable in amphibia and evolves itself in lacertilia into a columnar form which is characteristic of it.

It is difficult to see by what line of reasoning this latter columella could be regarded as belonging to the labyrinth region. It is much farther removed from the labyrinth region than a great deal of the pterygoid itself from which it is derived. This evident error would be of minor interest if it had no counterpart in the writings of more recent observers. Schimkewitsch, (Lehrb. d. vergl. Anat,, p. 121) describing the conditions in Sphenodon, states: From each pterygoid there reaches up a 'platten formig' bone (anti-epipterygoideum or columella cranii) which represents a process of the palatoquadrate which has already existed before in anuran amphibians." Although he deals with the homologies of this bone in almost all groups of reptiles, he neglects its description in the skull of the snake (figures from Boas) where (figs. 134 and 135) the term columella cranii is applied to the ear-ossicle whose internal end fits into the fenestra ovalis. If these two columellae are homologous it is puzzling that both should exist in the same reptilian form.


In higher mammals the auditory 'columella' seems to be represented by the staff-like portion of the stapes. There seems at present to be little doubt that the latter arises as a chondrification in the mesenchyme of the second visceral arch; our observations concerning this point are not, however, in complete unison. Concerning the origin of the plate-like cartilage which forms the distal (distal from the point of view of the visceral skeleton) portion of the stapes homologue which closes the fenestra ovalis there is very great diversity of opinion. According to one view, the entire stapes including the stapedial plate arises as a chondrification in the second visceral arch. Among the many observations supporting this view may be mentioned those of Baumgarten, Broman, Huxley, Keibel, Kingsley, Peters, Rabl, Reichert, Schenk, Schafer, Zittel, and Zondek; closely allied to this view we have phylogenetically the hyomandibular origin of the stapes, supported by Baraldi, Claus, Gegenbaur, Hasse, R. Hertwig, Ktikenthal, and Wiedersheim, and Parker. On the other hand, there are observations which tend to show that the entire stapes arises from the otic capsule, constituting then, a portion of the cranium and in no way related to the visceral skeleton. Among these observations may be mentioned those of Fuchs, Kolliker, Marshall, Parker and Bettany, and Wiedersheim. Minot derived the stapedial plate as an independent chondrification in the fenestra ovalis. These interpretations have been combined into a third dew according to which the stapes is formed partly from the otic capsule (i.e., the stapedial plate), and partly from the hyoid arch. This view of the mixed origin of the stapes has been supported by Gradenigo, van Norden, and Schultze. Giinther described the stapes as developing from the mandibular arch. Dreyfuss thought it developed from either the first or second arch. Cope and Frazer described the origin of the stapes as 'peri-arterial.' O. Hertwig regards its origin as uncertain. Finally one might mention the view of Siebenmann who would dismiss as immaterial the possibility of a definite relation of embryonic visceral cartilage and adult ear ossicles.


One must admit with Keibel (1912, p. 281) that there is great difficulty in tracing back a skeletal structure to the early pre-chondral stages, and it carries with it the danger of subjective interpretation." It seems desirable temporarily to set aside considerations of phylogeny and attack the problem from the point of view of the mechanics of development involved in a single ontogeny.


It is a well known fact that the crania of all vertebrates pass through a common phase of development which may be regarded as a ground-plan of vertebrate cranial formation. Surrounding the anterior end of the notochord there is found a parachordal cartilage, and anterior to this are located the trabeculae. In the meantime there have arisen three pairs of bilaterally symmetrical sensory epithelia — those of the nostrils, eyes, and ears. Each of these sensory epithelia becomes more or less completely surrounded by a prechondral cytoblastema which subsequently becomes cartilaginous. So striking is the intimacy with which each cartilaginous capsule adjusts itself to the contour of its respective epithelium, that it seems not unreasonable to suppose that each ej^ithelium in some way furnishes the stimulus which effects the chondrification of the surrounding mesenchyme. If this inference be correct, it is evident that the removal of a given sensory epithelium would inhibit the development of the corresponding cartilage. If this also be true, the early removal of the auditory epithelium would furnish a means of testing to what extent the stapes homologue together with its stapedial plate can develop in the absence of a cartilaginous otic capsule, or in the absence of the stimulus to which the latter owes its formation.


The work of W. H. Lewis ('04) is of great interest and importance in this connection. Lewis found that if the {{otocyst}} of an anuran be transplanted to the mesenchyme of a urodele, there develops around the transplanted otocyst a cartilaginous capsule which is typically urodelan in character. Unfortunately, experimentation of this sort is at present impossible so far as mammalian development is concerned. Avian development does, however, lend itself to this sort of procedure.

==Removal of the Otocyst==

Chick embryos of from thirty-five to sixty hours constituted the material for experiment. The experiments were of two types: 1) one of the {{otocyst}}s was coinpletely or incompletely removed by insertion into it of a very warm fine-pointed platinum needle, for a sufficient length of time to coagulate the liquid contents of the otocyst, whereupon the sensory epithelium would adhere to the needle when it was removed ; 2) the otocyst was transplanted.

After being subjected to this sort of treatment the eggs were sealed and allowed to incubate for various lengths of time — generally to an age at which the normal stapes on the uninjured side was well differentiated. A distinct advantage of this method is that the normal side serves as a control.

In general the results of the removal of the otocyst have been made known through a previous communication (Reagan, '14).

A preliminary study was made of embryos at an age in which the mesenchymatous tissue surrounding the normal otocyst was still in a prechondral or membranous stage. Figure 1 shows a section through the otic region of a chick embryo which had been incubated for five days. On the unoperated side there is a typically developed otocyst, around which the mesenchyme has begun to condense, staining rather deeply. On the operated side of the same embryo (right side of figure 1) it will be noticed that the otocyst is entirely lacking. The mesenchyme occupying the former region of the otocyst resembles in every way the other surrounding, lightly staining mesenchyme, and shows no evidence of condensation into an otic capsule. There was no attempt at regeneration of the removed auditory epithelium. This embryo had not yet developed visceral cartilages.



Fig. 1 Frontal section through the otic region of a five-day chick. On the left side an otocyst is present. On the right none is seen. The section is otherwise almost symmetrical. All sections figured in this account are viewed from their posterior faces so that the embryo's left corresponds to the reader's left. P. E. C. No. 1120. Int car., internal carotid; Int. j., internal jugular; Otcst., otocyst.

* 1 Princeton Embryological Collection.



We may now consider cases in which the embryos which had been operated upon were allowed in each case to live until the stapes of the normal side was well developed. Eight and nineday embryos were found to be most favorable for study.

Figure 2 represents a frontal section through the otic region on the normal side of an eight-day embryo from which the right otocyst was almost completely removed at the forty-fifth hour of incubation. The columella is seen lying between the external auditory meatus and the fenestra ovalis. Fused to the inner end of the columella is a flange-like ring of cartilage; but the two are everywhere separated by a distinct perichondrium which seems to be shared in common by the periphery of the mesial end of the columella and by the lateral internal surface of this flange of cartilage, the stapedial plate. A large part of the stapedial plate, or more correctly, the stapedial flange — projects freely into the mesenchyme. A portion of it, however, is continuous with the cartilage of the otic capsule, and seems always to have been a part of that cartilage. Situated inside the otic capsule is the auditory epithelium. The plane of section lies transverse to the transitional portion of the epithelium between sacculus and lagena. Mesial and dorsal to this epithelium is a portion of the acoustic nerve. A small branch of the internal jugular vein projects into the otic capsule. Dorsal to the capsular region, the facial nerve is seen emerging from its foramen. The plane of section is too far ventral to show the proximal connection of this nerve. A section in such a plane is shown in another embryo in figure 8. Dorso-anterior to the facial nerve will be noticed the large Gasserian ganglion, fibers from which are seen, in neighboring sections, to pass under the internal carotid. Mesial to the latter is the large internal jugular. Lateral to the carotid is the cartilaginous quadrate. Ventral to it is the parachordal cartilage which surrounds the notochord and is continuous laterally with the otic capsule. Ventral to the hind brain is the parachordal cartilage which surrounds the notochord and is continuous laterally with the otic capsule.

Figure 3 represents a frontal section through the operated side of the same embryo. This side presents striking contrast to the conditions just described for the normal side, inasmuch as certain structures are absent. The auditory epithelium has been removed. The otic capsule has failed to develop. The columella, similar to that of the normal side, projects mesially from the external auditory meatus. There is no stapedial plate. The inner end of the columella abuts against (but is not fused with) the parachordal cartilage. Some of the region which would normally have been occupied by the otic capsule has been invaded by the Gasserian ganglion, which seems to have migrated postero-ventrally and completely imbibed or fused with the facial ganglion. Thus it happens that in neighboring sections the large Gasserian ganglion appears to give rise to the facial nerve, which sends a branch to the anlage of the stapedius muscle or at least of a muscle in close relation to the columella. In most other respects the conditions are similar to those on the normal side.

Conditions similar to those in this embryo have been obtained in a large number of cases. It seems highly probable that the stapedial plate owes its formation to the same general stimulus which initiates the cartilage-formation that constitutes the otic capsule. Whether the stapedial plate is to be considered a part of the otic capsule, or as an independent formation in the fenestra ovalis is purely a matter of interpretation. The greater part of the stapedial plate seems to be structurally independent of the otic capsule, while a portion of it is fused with the latter probably from a very early time, seemingly having arisen from a part of the otic capsule. It seems reasonable to assume that the avian stapedial plate is not a part of the visceral skeleton. At any rate, if its constituent mesenchyme is a derivative of the second visceral arch, that mesenchyme is powerless to form a stapedial plate unless stimulated to do so by the auditory epithelium.


Figs. 2 and 3 Frontal sections of the otic regions of an eight-day chick from which the right otocyst was removed at a time at which the embryo was fortyfive hours old. Figure 2 shows the normal side while figure 3 shows the operated side in which a stapedial plate has failed to develop. P. E. C. No. 1117. Ac, acoustic nerve; Col., columella; E.a.m., external auditory meatus; Ephr., epibranchial cartilage; Fac, facial nerve; G.g., trigeminal ganglion; Gl., glossopharyngeal nerve; Int. cor., internal carotid; Int. j., internal jugular; Nch., notochord; Ot. cp., otic capsule; Otcst., otocyst; Par., parachordal; Qudr., quadrate; Rh., hind brain; Sq., squamosal; St. p., stapedial plate.




It has often happened that after the seventh day the columella became much flattened or irregular on its inner end. On the eighth day, this internal end was often found to have fused with some neighboring cartilage, sometimes with the parachordal, and sometime even with the quadrate. This may conceivably be an expression of its normal habit of fusing with a stapedial plate. Such abnormal procedure generally necessitates a bending of the columella from its normal direction. This tendency to fuse with neighboring cartilages seems to become even more marked in later development. In one case, for which I offer no explanation, the columella is bifurcated, one branch being fused with the parachordal, while the other branch (fig. 10) is curved dorso-laterally, its free end being connected with the external auditory meatus by a column of dense prechondral mesenchyme.

The plane of section of figure 10 on the operated side presents a picture quite similar to that in figure 168 in Lillie's "Development of the Chick." Owing to the great similarity of the quadrate cartilage on the right side of my figure 10 to that cartilage which Lillie had labeled 'Meckel's' cartilage, I feel convinced that Lillie may have misinterpreted the section of quadrate in his figure. On the left side of my figure the otic process of the quadrate extends dorso-posteriorly to unite with the otic capsule. External to this is the anlage of the squamosal.


It is of interest to note that if a very small portion of the otocyst be left in the mesenchyme, the latter will chondrify in the region of the small abandoned sensory epithelium and follow its contour very closely. If, for example, a small ventral portion of the otocyst be left in the embryo, it will take on the form of a hollow sphere which will generally be found in the region normally occupied by the lower portion of the lagena. The cartilage surrounding it will likewise be found to be a sphere. It may be of interest to state that in chemically treated teleost embryos it sometimes happens that both otocysts fuse more or less completely in the median plane. Whatever may be the configuration of the sensory epithelium, the developing otic capsule always conforms to the shape of the former. It seems well established that the cartilages forining about the three main pairs of sensory epithelia in the head are formed in response to the presence of those epithelia.

==Displacement of the Otocyst==

It was found that the {{otocyst}}, when displaced into foreign mesenchyme, caused cartilage-formation. It was hoped that both distinct otic capsule and stapedial plate might be induced to form from mesenchyme far removed from the head-region. The results of this sort of experiment are not yet sufficiently clear-cut to warrant their discussion. One case of displacement may, however, be profitably considered, namely, one in which the upper portion of the otocyst was transferred to a region which afterwards proved to be the foramen through which the facial nerve passed.


The embryo to be described was fifty hours old at the time of operation. A warm needle was introduced into the otocyst, the liquid contents of which became sufficiently coagulated that a pull of the needle was able to move the otocyst in the loose mesenchyme. The needle was pulled outwards and dorsoanteriorly and held in that position as steadily as possible for a considerable time. A small amount of warm Ringer's solution was allowed to run down the needle, drop by drop, until the needle could be pulled out of the coagulum. In this instance the entire otocyst did not follow the needle but pulled asunder, a small portion remaining in its original position; this fragment which was left behind assumed a spherical form. When the embryo was sectioned it was found that this hollow sphere of epithelium occupied a position symmetrical with the distal extremity of the lagena of the uninjured side, possessing like the latter, a cartilaginous capsule which appeared as a rounded projection of the parachordal cartilage. The displaced portion of the otocyst (figs. 5 and 9) may be interpreted as utriculus with perhaps a portion of the sacculus. The anlage of the endolymphatic duct, and in all probability a portion of the utriculus were destroyed. The remainder of the displaced epithelium, together with the intimately related acoustico-facialis ganglion are found to have occupied and dilated the foramen in the cartilage which is normally occupied by the geniculate ganglion and traversed by the facial nerve.


Figure 4 is a photograph of the normal side of a frontal section through the columellae of the embryo just described. The figure requires no explanation beyond that given for figure 2. Its chief value lies in the fact that it affords a comparison of the normal stapes with that of the operated side. The conditions of the latter are shown in figure 5, which is from the opposite side of the same section from which figure 4 is taken. The columella on the operated side resembles in size, shape, and position, that of the normal side. Auditory epithelium does not appear in this plane of section on the noral side. There is no otic capsule in this section. Coincident with this fact is that of the absence of a stapedial plate. It will be noted that two cartilages are present around the exit of the facial nerve. The more ventral one has a dorso-ventral direction, its lower end having as a base the lateral extent of the parachordal. This cartilage seems to be comparable to that which is found mesial to the auditory epithelium on the normal side. Dorsal to the facial nerve will be noticed a section of the cartilage which forms the roof of the capsule which surrounds that nerve. It is evident that the cartilages surrounding the facial nerves on the two sides are in every way comparable. There is reason to believe that these two cartilages, portions of the otic capsule, perhaps, have arisen in response to the presence of the facial nerve, acoustico-facialis ganglion, and the portion of the otocyst which was moved into the potential region of the foramen for the facial nerve. In some cases it was observed that the acoustico-facialis ganglion, by reason of its intimate connection with the otocyst, was removed with the latter, a cartilaginous covering for the nerve failed to develop. Examination of figure 3 might seem at first to afford evidence against this view, for we have here a facial nerve which is not surrounded by a cartilage. In figure 3, mesial and internal to the distal extent of the parachordal cartilage will be noticed an L-shaped cartilage which might conceivably represent the cartilage described as the capsule of the facial nerve in figure 5, having become displaced through pressure. The conditions might easily be correlated with the displacement of the trigeminal ganglion. There is perhaps another alternative. It might be assumed that the L-shaped cartilage or its normal homologue represents a portion of the parachordal complex which arises independently of the sensory epithelial tissue. In other words it might be assumed that not all of the otic capsule arises in response to the sensory epithelium, but perhaps in part to a stimulus from other nervous tissue. In figures 5, 6, and 10, it will be seen that a portion of the capsule surrounding the lagena on the uninjured side is represented on the operated side by a narrower parachordal.




Figs. 4 and 5 Photographs of the otic region of a nine-day chick embryo in which the right otocyst was early displaced into the region of the future exit of the facial nerve. Both figures lie in the same transverse plane. Figure 4 is through the normal side. Figure 5 is through the operated side. It shows the ventral-most portion of the displaced otocyst together with the facial nerve. These are frontal sections. P. E. C. No. 1118. Aud., auditory nerve; Col., columella; E.a.m., external auditory meatus: E. Col., extra-columella; Fac, facial nerve; G.^., trigeminal ganglion; GL, glossopharyngeal; Int. car., internal carotid; Otcst., otocyst; Par., parachordal; Qudr., quadrate; .S^/., squamosal; St. p., stapedial plate.





Figs. 6 and 7 Photographs from a section which passed through the greatest extent of the columellae of the same nine-day embryo from which figures 4 and 5 are taken. Figure 6 is from the normal side. Figure 7 is from the operated side. Note that the columellae are about equal in length and that there is no stapedial plate in figure 7. P. E. C. No. 1118. Qudr. at., otic process of the quadrate; T.p., tympanic pouch. (Other abbreviations as in figures 1 to 5). The upper portion of the tympanic pouch in figure 6 was unfortunately labeled 'Qudr. ot.'i



Figure 6 represents the normal region in a section of the same embryo, through the head of the columnella. It shows the relation of the facial nerve and its capsule. Figure 7 represents the operated side in the same plane of section as that of figure 6; the acoustico-facialis ganglion lies against the lower extremity of the otocyst. Sections in this region studied progressively towards the dorso-posterior region reveal the cavity of the transplanted portion of the otocyst. It is not difficult to see that the otocyst here occupies the foramen for the facial nerve, and that the acoustic and facial ganglia still preserve their intimacy of connection.


Figure 8 shows the normal side of a section somewhat dorsal to the plane of section of figures 6 and 7. The proximal portion of the facial nerve is seen entering its capsule on the mesial surface of the latter. Laterally this capsule is joined by the otic process of the quadrate. In the abnormal portion of this same section (fig. 9) one sees the capsule of the facial ganglion and nerve occupied by the sac-like otocyst; the latter more than fills the cavity at the inner entrance to the capsule and projects out into the scant mesenchyme between the cartilage and the brain-wall. Inside the capsule the sensory epithehum is surrounded by a vascular plexus. Where the auditory epithelium projects mesially towards the brain wall, it is internally covered by a perichondrium-like condensation of the adjacent mesenchyme which is continuous with the perichondrium of the cartilaginous capsule. Lateral to this capsule will be seen the otic process of the quadrate together with the overlying squamosal. In sections still more dorsad, the otic process of the quadrate is fused with the cartilaginous capsule surrounding the epithelial sac indicating the comparability of this cartilage to that of the unoperated side through which the facial nerve courses.

Figs. 8 and 9 Frontal sections through the region of the facial ganglion of this same nine-day embryo. On the normal side the facial ganglion (fig. 8) is shown. Figure 9 is the abnormal side of the same section in which the cartilage which would normally have surrounded the facial ganglion surrounds the entire otocyst. (Abbreviations as in previous figures. P. F;. C. No. 1118.)


If there exists a necessary nexus between the conditions above described and the deductions which have been made, it may be profitable to emphasize the following points:

The removal of the otocyst from young chick embryos seems entirely to do away with the stimulus to the later development of the otic capsule.

Embryos devoid of otic capsules fail to develop stapedial plates.

If it be objected that the removal of the otocyst produces the apparent inhibition by injury or removal of the mesenchyme surrounding the otocyst, it can only be urged that in case of mere transplantation it is unlikely that there was sufficient heat to injure the outlying mesenchyme when the auditory epithelium itself was not seriously injured. If it be objected that such formative mesenchyme was moved bodily in case of complete removal, it might be urged that such displaced mesenchyme failed to produce a stapedial plate in case of displacement of the otocysts. Furthermore, it seems improbable that the injury of the mesenchyme at the site of first invagination of the sensory epithelium should affect very profoundly the mesenchyme lying ventral to the hind brain in the potential region of the extremity of the lagena.

The columellar portion of the stapes of birds seems to penetrate the center of the stapedial plate (stapedial 'flange' or stapedial 'ring'), so that the central mesial surface of the columella actually forms a portion of the internal surface of the stapedial plate at least in embryos of eight to ten days. The present study has not determined the permanency of these conditions.

Whether the results here outlined demonstrate the stapedial plate to arise from the otic capsule, they certainly point to a possible kinship of the two structures, in that the same exciting stimulus is a factor in the production of each. The columellar portion of the stapes attains its full length and normal proportions in the absence of a stapedial plate; this fact offers a significant contrast in the nature of the latter structures. The stapeshomologue in birds seems to be of mixed origin, cranial and visceral.



It is evident that the development of the otic capsule and of the stapedial plate belongs in that class of phenomena which have been designated as the 'interactions of parts' and again as 'dependent development.' Hertwig ('94) was one of the first to attach great importance to those developmental process which are due only indirectlyto the original constitution of the fertilized ovum itself and likewise those due only indirectly to the external environment. These he designated as the "perpetually changing mutual relations in which cells of an organism are placed to one another." According to Herbst, all movements, tropic or tactic, and many processes of differentiation are responses of a formative, as well as a directive nature. Thus far the clearly demonstrated cases of interaction of parts are relatively few. Loeb has shown that the position occupied by the pigment cells on the yolk-sac of Fundulus is an oxygenotatic reaction. Several cases have been reported in which early displaced embryonic cells have resumed their original position.



2 Clark ('15j wrongly regards such phenomena as those in which hereditary constitution plays no part.



The development of certain parts of the vertebrate eye has been shown to be of a 'dependent' sort; there is, however, a certain amount of disagreement over the experimental results obtained by various observers. Spemann showed that if the formation of the optic vesicle of the frog be inhibited by injury to the medullary plate, or that if its approximation to the ectoderm be prevented, a lens will not form. Lewis obtained similar results on Ambly stoma. He showed that ectoderm from other regions transplanted to that region approximated by the optic vesicles would give rise to a lens. Schaper removed the entire central nervous system from a tadpole except the fore-brain and optic vesicles. He found that a lens developed in situ in the ectoderm and not as an infolding from it; he believed the lens was self-differentiating. On the other hand. King found that lenses might develop in the entire absence of an optic cup in the tadpole, while Mencl found the same to be true in an abnormal embryo of Salmo salar. In these two latter cases it is possible that stimuli exerted by the fore-brain itself caused lens-formation. Werber has shown that numerous isolated lenses may be developed m chemically treated teleost embryos in the absence of optic vesicles. Even here we may have a response to stimuli exerted by disrupted diencephalic tissue. The evidence in favor of self-differentiation of the lens seems to be entirely outweighed by the production of lenses in foreign ectoderm in the experiments of Lewis. Spemann and Lewis have also shown that the formation of the cornea is a response to stimuli from the optic cup, and will take place even though the lens be removed; that the cornea, once formed, degenerates with the removal of the optic cup. The work of Lewis on the formation of the amphibian otic capsule has already been mentioned. In a recent communication, I believe I have demonstrated that myocardial concrescence is a tactic response to the presence of endocardial tissue. Finally the stapedial plate is of interest in this same connection. If these several observations be confirmed, investigations of this sort may prove to be of extreme interest. It is probable that the interaction of parts is of greater importance than we are generally aware. In many cases we have reason to believe that in the earliest stages in the formation of many organs, a stage of equipotentiality of parts is not widely departed from, but that as development proceeds, totipotence is lost and powers of selfdifferentiation are more strongly asserted. In general one should expect from this that 'dependent development' would be a phenomenon confined to the earlier stages of ontogeny; there seem, however, to be certain exceptions to this. Of these exceptions, two sorts seem to be well established. First, it is a striking fact that many of the cases of 'dependent development' above discussed have to do with relatively late organ-formation. In fact it seems reasonable to suppose that the action of a differentiated part upon an undifferentiated one would be greater, the farther the activity of the former had advanced. The cases cited have to do with organ-formation in which the process is one of synthesis or 'composition' of rather diverse sorts of tissue. A second exception is that of non-differential cleavage or nondifferential development in which an apparently indifferent tissue sometimes maintains itself until relatively late in ontogeny, retaining its embryonic character and possessing several or many diverse potentialities. In case of an individual cell of such a tissue, one of these potentialities becomes realized while the others do not; this probably takes place in response to a stimulus. It seems highly probable that mesenchyme is a tissue of this sort. At any rate chondrification can be artificially produced in mesenchyme to form structures whose existence was most certainly not predetermined in the fertilized ovum; conversely, mesenchyme which would normally have chondrified can be prevented from so doing by the removal of the exciting stimulus to chondrification. It may well be that the diverse sorts of connective tissue and vascular tissue afford cases parallel to this in their development.


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