View source for Paper - On the relation of the chorda dorsalis to the anlage of the pharyngeal bursa or median pharyngeal recess (1912)

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| [[File:Mark_Hill.jpg|90px|left]] This historic 1912 paper by Huber describes early the chorda dorsalis to the anlage of the pharyngeal bursa or median pharyngeal recess. This paper uses embryos form Huber's collection and from [[Carnegie Collection]]: {{CE221}}, {{CE371}}, {{CE389}}, {{CE406}}
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=On the Relation of the Chorda Dorsalis to the Anlage of the Pharyngeal Bursa or Median Pharyngeal Recess=
[[File:G. Carl Huber.jpg|thumb|150px|link=Embryology History - G. Carl Huber|G. Carl Huber (1865-1934)]]
[[Embryology History - G. Carl Huber|G. Carl Huber]]

From The Wistar Institute of Anatomy Cell Biology

Seventeen Figures

==Introduction==

The pharyngeal bursa, first described by A. F. J. C. Alayer in 1840, const it littes a more or less clearly defined depression found in the pharyngeal vault in connection with the lower part of the pharyngeal tonsil usually having an upward and backward direction. There is a question as to the constancy of the existence of this structure in the adult, but its presence in early childhood is very generally admitted. There exists in the literature a diversity of oi)inion as to the origin and nature of the pharyngeal bursa. Luschka regarded this bursa as the remains of the oral hypophysial duct, basing his deduction on evidence gained from a human monstrosity, which was examined, however, only imperfectly. Through the more careful investigations of Dursy this view was shown to be incorrect. Schwabach regards what is known as the pharyngeal bursa as merely a crypt connected with the formation of the pharjmgeal tonsil. Killian regards this bursa as a structure sui generis. Robert Aleyer regards this bursa as found in. the adult as identical with the Seessel's pocket described for early embryonic stages. A number of observers have called attention to the fact that there exists a definite relation between the notochord and the pharyngeal epithelium in the region where the pharyngeal bursa occurs, and ascribe a causal relation to this union of notochord and the pharyngeal entoderm as concerns the anlage of the pharyngeal bursa, and it is to this phase of the ciuestion that the following more careful review of the literature and my own contribution is directed. For a more comprehensive review of the literature the reader is referred to the well known contribution of Killian, and to the brief but excellent exposition of the various views held concerning the origin and nature of the pharyngeal bursa as given by Oppel.


Froriep in his account of the development of the head portion of the chorda dorsalis in human embryos descril^es and figures the relation of this structure in a human embryo of 3.8 em., in which the notochord of the retropharyngeal region, that portion of the notochord which in the human embryo lies ventral to the spheno-occipital anlage, presented four enlargements. One of these is quite prominent, and is situated 1 mm. in front of the region Avhere the notochord leaves the ventral surface of the occipital cartilage. In this region there was observed an opening in the chordal sheath through which the chordal epithelium was directly connected with looped chords of chordal cells, which came in close relation to a well developed pharyngeal bursa. Whether the chordal epithelium was blended with the ]5har^^lgeal entoderm was difficult to ascertain. Concerning this Froriep expressed himself as follows: "]Man hat sogar l^ei gewisser Einstellung den Eindruck, als ob die Zellen des Epithels unci der Chorda sich unmittelhar bertihrten, jedoch nicht in so liberzeugender Weise, dass ich diese Stelle in die Zeichnung aufzunehmen gewagt hatte." Of the six human embryos investigated by Froriep, these varying in length to from 1.7 cm. to 8.8 cm., only one presented a distinct phar>^lgeal bursa. In discussing his results, this observer draws especial attention to the observation above referred to, as may be seen from the following statements : " Eine entwicklungsgeschichtliche Aktion scheint in (lessen dem Kopftheil der Chorda, wenigstens l^isweilen, zuzukommen, dieselbe erstreckt sich aber nicht auf den Schadel, sondern auf die Schleimhaut des Pharynx; es ist die Bildung der sogen. Bursa phar^^lgea." .... "Das in Fig. 3a aligel^ildete Praparat zeigt die Spitze einer embryonalen Bursa pharyngea eingesenkt in einen Haufen von Zellenstriingen, welche der Retropharyngeal-Chorda angehoren. Ein wirklicher Zusammenhang von Epithelzellen mit Zellen der Chorda ist zwar mit Evidenz nicht nachzuweisen, es clrangt sich aber bei der Untersuchung doch die Ueberzeugimg auf, dass diese fast zur Beriihrung fuhrend(^ Nebeneinanderlagerung der ])eiden Gewebs-individualitiiten keine gieichgiiltige sein kann. Die Wahrscheinlichkeit spricht dafiir, dass in den Fallen, wo eine retropharyngeale Chordaanhaufung his an das Epithel des Schlundkopfs vordringt, eine Beziehvnig zwischen l)eiden sich hersteilt, welche die Ijerlihrte Stelle der Schieim.haut oder ihrcs Epithels bei einer spater etwa folgenden Al:)drangung der Schlundwand von der Schadelbasis an dieser festhalt, and so jene trichterformige Ausstiilpung, die sogenannte Bursa pharyngea, zur Entstehung bringt." Some years later Nebelthau confirmed this observation of Froriep, as may be seen from the following ({uotation: "Eltenfalls scheint auch die ^'erm.utung FiT)rie]:)s, dass der '^^irbelsaite die entwickelun.g.sgeschichtliche Aktion. zukonnn,(>, (lurch ein.e en.ge B(^zichun.g zum


Ua('lu'ut']>itlu'l, cine {icwissc l'"ixi('iuufi ciucs Tcils soiiicr Zcllcii, jciutrichtt'iforiuigc Ausstiilpmifi, (lie sofj;. Bursa i)liaryuft(';i zur Juitstclnmg zu hriiificu. (lurch ilea Hci'uiul mciiics Pr;i])arat('s cine Stiitzc zu fiiidcu." Killian, whose Dhscrvatioii on the bursa and tousiUa i)haiyuf;('a have \)vvn trciiucntly (luotcd, stuchcd tliis i-csiou in (35 human ciuhryos, 3 newhorn aiul 2 chiKhcn, in all, 70 cases. The embryos and fetuses studied varied in aj^es from three months to eifi,id months. It is to be noted tiiat the younger stages are lacking. In 28 of the 70 cases studied (40 per cent), no l>ursa was present. The 42 cases in which a bursa Avas present he divides into such as presented a well developed bursa, 14 in all, and such as presented a more or less pronounced groove or funnelshaped de]iression, 26 in all. The region in question was studied macroscoi)ically in all cases; 20 of the cases, varying in age from four to eight months, were sectioned and studied microsco])ically. Killian recognized the fact that all of the eml)ryos studied, including those sectioned, were too old to i)resent suggestions as to the anlage and development of the bursa, neither does he find evidence for this in the well known AA'ork of His: "Ziu* Anatomic menschlicher Embryonen." For data concerning the earlier stages he mentions the observations of Froriep, above referred to. Killian reviews critically Froriep's theor}' that a phar^aageal bursa develops in case a retrophar>aigeal accumulation of chorda cells reaches the pharyngeal epithelium, and comes to the conclusion that this theory possesses the fault that it is l)ased on a single observation . Furthermore, since the l)ursa always develops in a definite region, namely — just in front of the u])i:»ermost fillers of the constrictor pharyngis super, which comes in close contact with the lower or posterior wall of the Ijursa as it lies between the heads of the musculi long, capitis, l^oth of which relations may be regarded as characteristic — while, as has l^een sho^m b}' Froriep, several accumulations of chorda cells which approach the pharangeal epithelium are found in the retrophar^aigeal region, and there is no reason why a bursa should not develop anterior to its normal position if close relation of chorda cells and pharyngeal epithelium are to ])e brought into causal relation as concerns the anlage of the pharyngeal bursa. Killian also dismisses the lig. occipito-phar. as a factor in t,he development of the bursa and the fact that in a number of his cases the oral hypophysial duct and the l^ursa were })oth present and separated bj' appreciable distances, excludes the view that persistence of the hypophysial duct and the cranio-phar^aageal canal may be regarded as the anlage of the pharjiigeal bursa. Killian, therefore, regards the bursa as a 'true epithelial outgrowth,' as ma,y be seen from the following statement, summarizing his discussion of the anlage of this structure: "Ich betrachte also die Bursa phar^iagea em])ryonalis als eine wahre AusstulpungderRachenschleimhaut nach hint en und ol^en gegen das Hint erhauptsl^ein, wobei speciell im Epithel das formative Princip zu suchen ist. Sie verdankt nicht mechanischen EiuAvirkungen, sondern einem aktiven Bildungsvorgange ihre Entstehung." Killian presents further very extended comparative anatomic studies, which it would be impossible to cite here in detail. It mav be stated, however, that his results in the main were negative, in that no l:)ursa pharyngea was present in the great majority of the types investigated including representation from vertebrate classes ranging from primates to amjihibia. A true pharyngeal bursa as found in man was ol)served only in Arctomys marmota, although th(> pig, deer and bear presented structures which have been regartled as jihar^Tigeal bursae, and may be homologues of this structure as found in man. Schwaliach treats of the median pharyngeal bursa in two contributions. In the first of these he discusses observations made on 52 heads, of which 28 were of children ranging in age from one day to three years; to these may be added a human fetus of six months. As a result of these studies he is led to believe that the pharyngeal bursa of Luschka represents merely the end of the median depression found in the pharyngeal tonsil, therefore, is not to he considered an anatomic entity, l)ut a ]iart of the phar\iT.geal tonsil. In the second contribution Schwabach treats of the development of the pharj^iigeal tonsil. In all, 45 embryos were studied, of these 43 presented a crown-rump length of 3.1 cm. or more. Ii">. these the vault of the pharjux was exposed by removal of the lower jaw and other necessary parts. The preparations thus obtained were thenexaro.inedmacroscopically; certainof them were then cut in sagittal or frontal sections. Two other embryos of 1.6 cm. and 2.8 cm. croA\7a-rump measurement were cut in sagittal sections. In embryos of less than 6 cm. length no evidence of any depression or infolding of the phar^mgeal vault was ol)served. In embryos ranging from 6 cm. to 7 cm. in cro^\^).-rmnp length there was noted in the median line at the transition of the fornix to the posterior pharyngeal wall a shallow depression or groove which was regarded as the anlage of the pharyngeal tonsil. This depression is said to have reached its maximum in embryos of from 9 cm. to 10 cm. crown-rump length, after which period of development the depression again became shallower, as the adenoid tissue of the phar^mgeal tonsil became evident. Kolhker in his brief discussion of the head chorda makes no mention of its bearing any relation to the phar\aigeal l)ursa, which latter structure is not considered in this connection. In a l)rief note, entitled "The Notochord of the Head in Human Embryos of the Third to the Twelfth Week," Mrs. Gage expresses very clearly and correctly the relatioiis existing l^etween the head chorda and the pharjaigeal entoderm, as the following abstract may show: "In a human specimen of sixty days the relations of the notochord to the cartilaginous base of the skull and the epithelium of the mouth are clear. On emerging from the axis it forms a knotted protuberance dorsal of the base of the skull, passes diagonally through it to a pocket from the roof of the mouth, thence cephalad to come in contact with two other mouth pockets, thence diagonally dorsal through tlie base of the skull, again forming a knot and turning shar])ly ventrad, ending near the hy])oi)hysis, but within the (cartilage." The same relations exist in a specimen of forty-eight days, and at thirty-six days where a condensed mesoderm foreshadows the skull, and at twenty-eight and twenty-one days where the notochord lies directly in contact with the epithelium of the roof of the mouth, thus showing the beginning of the history, Mrs. Gage further reports briefly on a comparative study of head choida ot the ])i^', >h('c|), call, mouse, cat. cliick, amlilvsloiiia, l"i\)j;', shark and lamprey, and shows that the iiotochoi-d alter the earliest staji;es is usually completely se])arated from the i-oof of the mouth. In the ])!•;■, however, ahout 20 per cent were similar to man, heinft- in coiitactt with mouth pockets. Mrs. (!afj;e has A-ery kindly sent me a miml)er of i)hotomicrof>rai)hs of the hea(l region of a uuml)er of human embryos of the Cornell series, cut in very favoral)le sagittal sections, w'hich show \-er>- cl(>arly the relations of the notochord as described by her; for this I desire to ex])ress my sincere thanks.


CJiusei)])e Levi in his study of the develojjment of the caiiilaginous ])rimordial cranium, considers the relations of the head chorda in the human embryos at his disposal. In one of the embr>'os studied by him, his embryo />', greatest length 14 mm., he states that the notochord after reaching the ventral surface of the l)asal))late and after coursing in the perichondrium for a shoi-t distance, passes into the retropharyngeal connective tissue; "wo sic mit dem Epithele der Bursa i^lunyngea einen innigen Zusammenhang hat." In the other embryos studied no such relations were observetl. Goppert in his discussion of the development of the oral cavity and its organs in the 'Hertwig Handbuch,' gives brief consideration tothe development of the Bursa i^haryngea, quoting largel}' from the studies of Killian, ]:)reviously considered, and accepting his views. Gauj^p in his chapter on the develoi^ment of the head skeleton in the 'Hertwig Handbuch' considers the relations of the head chorda to the l)asal ])late. The relations as fomid in ral)ljit and human embryos are chiefi}- discussed, for the latter the description given is based mainly on the observations of Froriep, previously noted; no mention is made of the relations of the head chorda to the phar^mgeal epithelium. Williams in his stud,y of the development of the notochord, especially in that portion which deals with the relations of the notochord to chordoma, considers the head chorda in a 32 mm. human embryo (H.E.C., Xo. 292) giving an illustration, his figure 20. This figure shows the head chorda as incorporated in the cartilaginous basal plate, and lying near the surface of the cartilage at four points. "It is near the upper surface, in the hypophysial fossa, a short distance behind the fossa, and near the foramen magnum and near the lower surface at a point midway between the hypophysial fossa and the foramen magnum." This, it is stated, is the normal course of the notochord in the skull of human embryos, its curve being due to the fact that the notochord remains attached to the epithelium of the vault of the pharynx longer than elsewhere, the mesenchyma which grows in between the base of the brain and the phar^mx collects, therefore, above the middle portion of the notochord. Williams furtlier states that this middle section of the notochord bears a variable number of kinks, short branches and thickenings which he often finds involving the pharyngeal epithelium, which is here thickened and often invaginated. Special mention of the relation of the head chorda to the epithelium of the pharAmgeal bursa, if this was noted, is not given. Meyer, ia a brief note, draws especial attention to the relation of the chorda to the development of the median pharAiigeal bursa or recess in human emliryos. A concise statement of his findings in human embryos varying from 2.5 mm. to 40 mm. in length is given, in all of wiiich he shows a more or less close relation of the chorda to the epithelium of the pharyngeal bursa. His results are summarized as follows: "Aus meinen Befunden an jiingeren menschlichen. Eml)ryonen geht hervoi", dass die Bursa pharyngea unabhiingig von der Rathkeschen Tasche im 2. Monate bei ca. 14-28 mm. Scheitelsteisslange mi.gefahr miter 5 Fallen einmal zur Ausbildung kommt unci stets mit der Chorda im Zusammenhange steht. Ich habe daraus die Anschauung gewonnen, class als direkte Ursache der inkonstanten Bm-sabildung beim Embryo eine Persistenz der ursprlinglichen Verbindung zwischen Chorda and Rachenentoderm anzuschuldigen ist, also eine mangelhafte Losung zwischen Ijeiden." In this note Meyer cites the observations of Griinwald on sheep eml)ryos, to Avhich I shall refer later, who records that the anterior end of the chorda remains in contact with the pharyngeal membrane and ultimately with the e])ithelium of Seessel's pocket, and further, that Froriep had previously called attention to the contact of the anterior end of the chorda with the epithelium of Seessel's pocket in chick embryos, and that Staderini had shown, similar relations for rabbit and sheep eml)ryos. This leads Meyer to conclude, that "Der Umstand, class die Bursa pharyngea der Erwachsenen ebenfalls an der Schadelbasis fest adharent gefunden wird, weil sie die Fil)rocartilago basilaris durchbohrt, erlaubt den Schluss, dass die Bursa pharyngea media der Erwachsenen mit der bei Embryonen beschreilienen, also der Seesselschen Tasche identisch ist." Linck in an extensive contribution on the chorda dorsalis in the head and neck regions of human embryos, in which embryos varying in length from 2 cm. to 25 cm., head to foot measurement, with leg extended, are very fully considered, deals fully with the relations of the head chorda to the pharyngeal bursa. This relation is further considered by Linck in an especial contribution dealing with the genesis of the eml;)ryonic pharyngeal liursa, a contri])ution which must be regarded as the most comprehensive and accurate of all dealing with this sul)ject. In nine of the sixteen embryos studied there was present an embryonic pharyngeal l)ursa. In only one of the nine embryos considered as presenting this bursa, however, is there direct contact of chorda tissue and pharyngeal epithelium, and in this embrj^o. No. 1, 2 cm. length, this contact must be assumed, since the pharyngeal epithelium was in large part wanting, owing to m.aceration. In the other eight eml:)ryos presenting this bursa, which is figured for nearly all of the prejjarations in one or the other of his two publications, there w^re ol)serv(>d chordal remains in more or less close relations to the lilind end of the phar^aigeal bursa enclosed within a more or less clearly recognized strand of (leveIo])ing connective tissue extending between the region of exit of the chorda from the basal plate to the blind end of the phar^mgeal bursa. Linck recognizes as causative factors in the development of the embryonic i)haryngeal bursa the attachment of the chorda to the pharyngeal e])ithelium in a region corresponding to about the middle of the basal plate in early embryonic stages, and tension on the chorda resulting by reason of a caudal elongation of the basal plate in further growth, this ;iccom]i;iui('(l liy ;t t hi<'k('uiu{;' of the rclrophai-viiKcnl councftivc tissue ;is jj;i'i)\vtli |)i-()ct'{'(ls, as iua>' lie seen tVoiu the lollowiiif;" extract taken from his sumiuai'>': "Diese stets an eiuer typischeii Stelle, urspriiuj;li('h etwa iil)er dcr Mitte des ( Jruu(lkn()r])els, {>;elef;-eiie VerhiiuhiUK zwiseheu Chorda dorsalis iiud Hacheuoherllache l)riii<>;t iiu Vereiii mit deiu Diekeuwaclistum der Hacheiihaut uud deiii uu{ilei('linKissip;en Jiaujieiiwaehstum des os hasihirc cincn Mcchauisnius zustaiule.wclchor hcwirkt, dass der aul'stcigeude C'hordaschenkel auf die Sehleimhautobertliiciio (>inc>n ehistischen Zug ausiibt und eino Kaudahvjirts gerichtete l*]]iith(>h'instiilpung, die Bursa pharyngca embryonalis, hervorbringen knuu." I shall refor again to the contril)utious of Linck after presenting my own observations.


The niatt^rial on wliich my own observations were made includes hmnan embryos from Professor Mall's collection, mainly younger stages, and from my own collection. Only embryos cut in sagittal sections and of at least fairly good preservation are included. In. all, 15 emljryos, varying in crown-rinnp or -breech length, from 6.6 nmi. to 145 nun. were especially studied, and, as will be observed, the embryos selected form a fairh^ complete series between the lengths given.. Of nearly all there is given an outline drawing of a mid-plane sagittal section of the head, particular attention being paid to the head chorda and its relation to the pharyngeal epithelium, as also the pharyngeal bursa whenever this was present. These figures were made by graphic reconstruction. The reconstruction was, however, not extended in all of the figures, so as to attain a mid-plane sagittal section of the nervous system, nor the tongue region. The detail figures, la to 14a, were drawn by aid of camera lucida at a magnification of 300 diameters, reduced in reproduction so as to give a magnification of 100 diameters, and for the greater part were drawn from a single section. A few of these figures are combined from the drawing of two or three sections. Each detail figure includes a special region where the notochord comes in contact with the pharjaigeal entodemi, for the younger stages, a region which I regard as the seat of the pharyngeal bursa; for the older stages, the region of the pharpigeal bursa and surrounding retropharyngeal tissue is given. The data here given were presented by way of demonstration at the Boston meeting of the American Association of Anatomists, December, 1909, and again in an address with projection demonstrations given at the College of Physicians and Surgeons of Philadelphia in May, 1911. The present presentation seems warranted by reason of the fact that the series of embrj'os on which this study is based, includes the essential younger stages lacking in the contribution of Froriep and Linck, and I hope to make clear that these younger stages show that the pharyngeal bursa bears no relation to Seessel's pocket as is postulated by Meyer. I may now proceed with a brief consideration of the material at my command.


Embryo A, No. {{CE371}} of the Mall collection, 6.6 mm. length. Figure 1 and figure la. There is present a large and well jfixed notochord which after it passes through the denser mesenchyme of the vertebral anlagen, bends sHghtly ventrally beneath the denser mesenchjane, the anlage of the basal plate. In the region where the notochord bends ventrally to pass beneath the anlage of the basal plate it presents a slight enlargement and comes in contact with the pharyngeal epithelium. The notochord touches the epithelium again slightly cephalad to this area, and again just before it bends dorsally near its cephalic end. Otherwise the notochord is completely separated from the pharyngeal epithelium by one or two rows of nuclei of the mesenchyme. The extreme cephalic end of the notochord presents a slightly wavy and spiral course and bends ventrally to reach the pharyngeal epithelium just caudal to Rathke's pouch, as is shown in figure 1. The extreme anterior end of the notochord is somewhat difficult to make out clearly, and it is not possible, therefore, to state with certainty that the tip end is actually in contact with the pharyngeal epithelium. The region where the notochord first touches the ])haryngeal epithelium as one passes from the caudal to the cephalic portion of the pharyngeal vault, just after the chorda bends ventrally to pass into the retropharyngeal region, near the right upper end of figure la, represents the place of development of the pharyngeal bursa. This region of contact of notochord with pharyngeal epithelium is constant and characteristic for the younger stages. It is always caudal to the thyroglossal pit in the tongue, lower left side of figure la, though the distance varies somewhat, due no doubt to the extent of flexion of the head. The place where the cephalic end of the notochord terminates in this embryo is the region of Seessel's pocket, though a distinct pocket is not observed in this preparation, and it is a question whether this pocket exists in the liuman embryo. It has been shown that the notocliord ends in Seessel's pocket in chick, rabbit and sheep embryos in early statics of development. I'lic same sccius. t licrd'oiv, true in the huinaii cmlii-yo. riic tact tliat in J'hiilii\\() .1, of this series, the area of contact of notoclioni and i)haryiifi,cal ('])itli('liuin, indicatinji; tlic r('j;"ion of (Icvclopnicnl of the ])hafvn<i('al l)Ui-sa and the cxtrcnic anterior point of contact in tlie region of Seessel's ])ockel may liolh lie made out and soi)arated 1)V practically the whole len<!;th of the ])haryn<i;eal vault, would seem to me to suflice to controvert the contention t)f IMe^'er that the pharvnii'eal iiui'sa de\('lops from Seessel's pocket.

E.MHuvo B. Xo. 221, ]\lall collection, 7.5 mm. Figure 2 and figure 2a. This series is not deepl}' stained, so that it is somewhat difficult to make out distinct differences in the density- of the mesenchyme. The anlagen of the vertebra, therefore, not very distinct. The undulations of the notochord described by Minot well shown. The denser mesenchyme of the anlao-en of the vertebra extends forward into the denser mesenchyme found ventral to the brain tube, the anlage of the basal plate. Tne notochord just after it bends ventrally into the retropharyngeal region comes in contact with the pharyngeal epithelium whicli is distinctly thickened in the area of contact, (fig. 2a) upper right hand portion of figure. For a distance cephalad of this area of contact it is somewhat difficult to make out clearly the course of the notochord and its relation to the pharyngeal epithelium. It appears to course just over the epithelium, with here and there a mesench^Tnal cell between. The want of distinctness of the notochord in this region is partly due to the fact that the pharyngeal epithelium presents a distinct kink dorsalward, situated a short distance cephalad of the thyroglossal pit in the tongue, in which region all of the retropharyngeal structure are l^ent dorsally. The arrangement and apparent compression of the mesench}Tne suggests that this kink is an artefact. Just cephalad of this kink the notochord is again clearly made out, and here again touches the pharyngeal epithelium just before it bends dorsally to end in the denser mesenclnane of the basal plate anlage. Just before the cephalic end of the notochord is reached it presents a ventral ofT-shoot, which is, however, not clearly followed to its termination. This off-shoot seems to me similar to the ones described by Griinwald for sheep embryos as the remains of the ventral extensions of the notochord which ends in Seessel's pocket.

Embryo C, No. {{CE389}}, JNIall collection, 8 mm. Figure 3 and figure 3a. This embryo is slightly macerated, as indicated bj' the Retzius folds in the brain tube and the appearance of the mesench^Tne. The pharjTigeal epithelium not macerated and in place. The vertebral anlagen appear as distinct blocks of denser mesenchj^me which extends forward as a denser layer of mesenchyme, the anlage of the basal plate. The notochord makes a distinct loop just after it bends ventrally to pass into the retropharyngeal region beneath the anlage of the basal plate. The end of this loop is bifid, both parts coming in contact with the pharyngeal epithelium. The notochord then courses along over the pharyngeal epithelium, presenting slight undulations, and here and there just touching the pharyngeal epithelium, then turns dorsally with rather irregular contour, to end near the top of Rathkes pouch, as shown in figure 3. All along its course in the retropliaryng(>al region mesenchyme is found between the chorda and tlie pharyngeal epithelium. The relation of the notochord, as also the distinct loop and region of contact between chorda and the pharyngeal epithelium is cl(>arly shown in figure 3a.





Fig. 1 No. {{CE371}}, Alall collection, Embiyo A, 6.6 mm. Reconstructed outline drawing of midplane sagittal section of head. Notochord black. X 10.

Fig. 2 No. {{CE221}}, Mall collection. Embryo B, 7.5 mm. Reconstructed outline drawing of midplane sagittal section of head. Notochord black. X 10.

Fig. 3 No. {{CE389}}, Mall collection, Embryo C, 8 mm. Reconstructed outline drawing of midplane sagittal section of head. Notochord black. X 10.


Fig. hi No. {{CE371}}, Mall collection, Embryo .1, 0.6 mm. Drawing shows vault of pharynx and dorsum of tongue. Xotochord in contact with pharyngeal epithelium near upper right portion of figure. X 100.


Fig. 2o No. {{CE221}}, ]\Iall collection, Embryo B. 7.5 mm. Drawing shows vault of i)harynx and dorsum of tongue. Xotochord in distinct contact with pharyngeal epithelium, which is thickened in area of contact. X 100.



Fig. 3a No. {{CE389}}, Mall collection, Embryo C, 8 mm. Drawing shows vault of pharynx and dorsum of tongue. Notochord makes distinct loop — upper right hand portion of figure — and comes in contact with the pharyngeal epithelium. Other less distinct points of contact of chorda and the pharyngeal epithelium shown. X 100.



Embryo D, No. 3, Huber collection, 10 mm. Figure 4 and figure 4a. Very well preserved hiaman embryo, cut in sagittal sections of 5/x thickness. Vertebral anlagen present as very distinct blocks of denser mesencliAane. Denser mesenchjane extends cephalad as the anlage of the basal plate. Pharyngeal epithelium well preserved. The notochord as it bends ventrally to pass into the retropharyngeal region, beneath the anlage of the basal plate forms a distinct loop which comes in contact with the pharyngeal epithelium. In this area the epithelium presents tAvo irregular rows of nuclei, while for the remainder of the pharyngeal vault the epithelium is simple, with a single row of nuclei. In the series of sections the caudal portion of the looped notochord appears first. The cephalic end of the loop begins to appear in the fourth following section, showing that the chorda at the bottom of the loop is also bent laterall^^ Figure 4a represents a reconstruction drawing made from the three most favorable sections of this region. This drawing does not show as clearly, as may be seen by tracing through the series the direct contact between chorda and pharyngeal epithelium, which contact is most distinct against the side of a small fold of pharyngeal epithelium, difficult to represent in the drawing. Cephalad to this region, owing to a shght deviation of the head from the mid-plane, the notochord is traced, obliquely cut, through 25 sections of the series to its end near the upper end of Rathkes pouch. Near its anterior end the notochord, just before it turns dorsally again touches the pharyngeal epithelium in two places, for the remainder of its course in the retropharyngeal region it is distinctly separated from the epithelium by a small amount of mesench^Tne.


Embryo E, Mall collection, No. {{CE406}}, 13 mm. Figure 5 and figure oa. Well stained and well preserved series. Practically the whole of the head chorda, from where it leaves the anlagen of the vertebra to its cephalic end embraced in one section. Vertebral anlagen and basal plate in stage of precartilage, and clearly outlined. As the notochord bends ventrallj^ to pass into the retropharyngeal region beneath the anlage of the basal plate it presents a trilobed ventral extension, which extends practically to the pharyngeal epithelium, in a region just over the thyroglossal pit in the tongue. A few mesenchymal cells have grown in between this ventral extension of the chorda and the pharyngeal epithelium, so that it seems even in this region completely separated from the pharyngetil epithelium, though in very close relation with it (fig. 5a). In the remainder of its course in the retropharyngeal region the notochord follows closely along the ventral side of the denser mesenchyme bordering the precartilage of the basal plate, and is separated

l)\- S('\cr;il l;i\t'fs of iiicsciicliN iii;il nuclei tVoiii I lie |)li;ii-\iiu:c;il I'pit licliiiin. Near its ccplKilic ciid the uotocliord liciids doi-sally lo icciitci' tlic ;iul;ifi;e of the \k\<-A i)l;it(', in which it t ci'iuiiiatcs iicaf Jiathkcs poucli. The ])har\-nti(':i,l vault of this cinlnyo pi-cscnts a distinct dorsal kink, somewhat cephalad of the t h>'i-(),i;'lossal pit of the tonj;iie. The notochord

ind nu'sench>ine are likewise bent doi'sally in this ro<i;ion, as may b(! setMi from fiuui-e '). This is looked ujion as an artefact.

IvMHKVo !•', Huher collection, Xo. 4, 1") mm. li<>;ure (i and fi}i;ure tW/. Vertebral anlaj;-en in sta^e of eml)ryonie cartilage, as also basiocei))ital. The notochord as it leaves the vertebral anlagen passes dorsal to the cartilaginous basioccipital, through tlie caudal end of which it bends ventrally to reach the retropharyngeal region. Just after it reaches this region the notochord ])resents a distinct, triangular shaped, ventral extension, which comes in contact with a shallow ])it lined by a stratified pliaryngeal ei)itlielium, a pit which is regarded as the anlage of the pharyngeal bursa. This ventral chordal extension does not rest on the top of the infolded ])haryngeal pit. but a little to its side, so that the chordal extension and the ]ihar>-ngeal pit appear in the four sections preceding the one from which figure^ 6a was drawn. In two of these sections the contact between chordal and pharyngeal epithelium is intimate, much more so than in the section from wdiich the figure was taken. The condition here presented ap])ears to me very similar to that found in Embryo 7, of Linck's series, except that the pharyngeal epithelium in Embryo F, is in excellent state of preservation, so that its relation to the chordal cells could be clearly made out. In this preparation there is no question of the direct contact of the notochord with the pharyngeal epithelium in the region of the forming pharyngeal bursa. A slight distance cephalad of this region the notochord again comes in contact with the pharyngeal epithelium, presenting tw^o ventral extensions with common base, both extensions reaching the epithelium which in this region is also thickened, however, there is no evagination. The notochord then passes along the ventral surface of the basioccipital, presenting three further ventral extensions wdiich do not reach the pharyngeal epithelium, then bends dorsally to reenter the basioccipital in which it ends near the hypophysial anlage, which shows the first stages of separation from the oral epithelium, in that the dorsal vesicular portion is attached to the oral epithelium by means of a solid chord of cells.

Embryo G, Huber collection. No. 6, 16 mm. Figure 7 and figure 7a. The vertebral anlagen and basioccipital in stage of embryonic cartilage, the dens epistrophei outlined in dense mesenchyme, the hypochordal arch in precartilage. The head chorda almost through its entire length


Fig. 4 No. 3, Huber collection, EmbiyoZ), 10 mm. Reconstructed outline drawing of midplane sagittal section of head. Xotochord black. X 10.

Fig. 4a No. 3, Huber collection, Embrj^o D, 10 mm. Drawing of portion oi vault of pharynx and dorsum of tongue. Xotochord shows distinct loop in contact with pharyngeal epithelium. X 100.

Fig. 5 No. 406, Mall collection. Embryo E, 13 mm. Reconstructed outline drawing of midplane sagittal section of head. X'^otochord black. X 10.

Fig. ha Xo. 406, ^Nlall collection. Embryo E, 13 mm. Drawing shows portion of vault of pharj-nx and dorsum of tongue. Distinct ventral extension of notochord, just over thyroglossal pit in tongue, which is not quite in contact with pharj-ngeal epithelium, a few mesenchymal cells intervening. X 100.

Fig. 6 No. 4, Huber collection, Embrj'o F , 15 mm. Reconstructed outline drawing of midplane sagittal section of head. X'^otochord black. X 7.5.

Fig. 6a No. 4. Huber collection, Embrj-o F, 15 mm. Drawing showing portion of vault of pliarynx and dorsum of tongue. Distinct ventral extension of notochord in contact with an evagination of the pharj-ngeal epithelium the anlage of a pharj'ngeal bursa. Further point of contact of notochord and pharyngeal epithelium to the left in figure. X 100.

is embraced in one section. The notochord surrounded by a distinct chordal sheath passes obhquely through the caudal portion of the basioccipital to reach the retropharyngeal region in which region, through its entire course, it is in close relation with the ventral surface of the basioccipital. Just over the region of the thyroglossal pit in the tongue, the notochord presents a bilobed, ventral extension, which passes obliquelyCin a cephalad direction to near the pharyngeal epithehum from wliich it is separated, however, by a layer of mesenchymal cells. The pharyngeal epithelium of this region is not evaginated, nor is it thickened; there is no evidence, therefore, of the anlage of a pharyngeal bursa. The notochord presents several ventral bulgings which do not reach the pharyngeal epithelium before it bends dorsally to end in the basioccipital near the anlage of the hypophysis, which is almost completely separated from the oral epithelium.


Embryo H, Huber collection. No. 32, 19 mm. Figure 8 and figure 8a. This embryo was slightly macerated, as is shown by the Retzius folds of the brain vesicles, not reproduced in figure 8. Pharyngeal epithelium and mesench^'mal structures fairly well preserved, epithelium in place. The vertebral anlagen and basioccipital in stage of emliryonic cartilage and well outlined. The notochord after leaving the vertel^ral anlagen passes obliquely through the caudal end of the basioccipital to reach the retropharyngeal region. Almost immediately after reaching the ventral surface of the basioccipital the notochord presents two ventral extensions. The posterior of these is of leaf-shape and does not ciuite reach the pharyngeal epithelium, while the anterior of the two extensions is of cylindrical shape and comes in contact with the epithelium of an evaginated portion of the pharyngeal wall, the anlage of a pharyngeal bursa. The middle of the bursa is not cut in the section figured, so that the epithelium appears greatly thickened, due to the fact that it is in part cut tangentially. It is for this reason also difficult to speak with certainty of the exact relations presented by the chordal epithelium. It would appear, however, that the chordal epithelium is in direct contact with the pharyngeal epithelium, without the intervention of mesenchyme. The notochord presents another, a club-shaped ventral extension slightly cephalad to the i:>haryngeal bursa, which does not reach to pharyngeal epithelium, l)eing separated from it l^y a layer of mesenchyme. Then after coursing along the ventral surface of the basioccipital for a short distance the notochord l)ends dorsally to end in this in the region of the hypophysial anlage. The craniopharyngeal canal is nearly obliterated, containing a slender interrupted chord of hypophysial cells. Above the seat of the original attachment of the oral hypoi)hysis anlage which is still evident in the oral epithelium there is found in the mesenchymal mucosa a small mass of hyi^ophysial epithelium, a remnant of the hypoi)hysia,l duct.

Embryo I, Huber collection, No. 38, 25 mm. Figure 9 and figure 9a. Embryo slightly macerated, as is shown l)y the Retzius folds in the

l)i':iiti \('^icl('s, nol sHowiNG in timirc 'J. I'ipit licliiiiii sli^ililly iiiaccnil <■(!, t lioimh ill placf (»\('r t lit' greater part of I he |)liaiAii<i;cal \aiilt. Vort('l)ral aiilaut'ii ainl the l)asit)ccii)ilai in cart ilaj^c staj;*'. <l«'n< cpist roplici and liypoclionlal arch in static of cniliryonic cartilajic Tlic notocliord with well developed clioi'dal sliealh can he traced as a continuous chord somewhat retracted fri)ni tiie sheath, from tiie dens epis1roi)hei to the dorsal surface, thence to tlie ventral surface of the basioccipital, throujih the eaudal end of which it ]);is.ses oI)li([Uely, to extend aloiiji its ventral surface for a short distance. From tliis region there extends vent rally a sleiidm" extension surrounded by a tiiin chordal sheath, which may be traced neaiiy to the blind end of a ])harvngeal evagination, with narrow lumen, and of cylindrical shape, the anlage of a i)haryngeal bursa. The chordal cells cannot hv traced quite to the pharyngeal epithelium, though no m(\-enchyme intervenes. The impression is left that during fixation the two parts had separated, owing to contraction. Cephalad to the region of the pharyngt^al bursa th(> notochord was fixed in processes of breaking down, though if many sections are coml)ined a continuous structure may be made out, as is shown in figure 9. The section from which fii;ure 9a was taken, that section in which the pharyngeal bursa was most clearly shown, presents the notochord cut twice in the retropharyngeal tissue, the thick chordal sheath may here be seen, as also the contracted chortlal tissue. The notochord finally bends dorsally^ to end in the basioccipital some little distance from the hypophysis. The craniopharyngeal canal is practically obliterated. The place of origin of the hypophysis is marked in the oral epithelium by a slight evagination. .Just dorsal to this end and still attached to the oral epithelium there is found in the mucosa, a vesicle of oval shape, epithelium lined, developed from the hypophysial stalk.

Embryo J, HuBer collection, No. 47, 32 mm. Figure 10 and figure 10a. This embryo which was received while still warm, from the service of Professor Peterson (hysterectomy for large filn'oma), in excellent state of preservation, was cut into a practically faultless series of sagittal sections of 15m thickness. The cartilaginous cranium w^ell developed. The notochord after leaving the dens epistrophei take^ a tortuous course to the dorsal surface of the caudal end of the basioccipital. In its course through the cartilage the notochord may he traced bj-" an empty though well developed chordal sheath. The epithelium of the chorda appears again as the ventral surface of the basioccipital is reached, and may in the retropharyngeal tissue be traced to the blind end of a deep, cylindrical shaped evagination of the pharyngeal epithelium, a well developed pharyngeal bursa, well shown in figure 10a, drawn from the section in which the pharyngeal bursa was most clearly portrayed. In its course through this portion of the retropharj^ngeal region the notochord is closely surrounded by dense strands of developing connective tissue which run parallel with it. It is not possible to trace the chordal epithelimn to a contact with the pharyngeal epithelimn, although the chordal sheath may be traced to the immediate vicinity of the pharyngeal epithehmn, so that it becomes attached to the bhnd end of the pharyngeal bursa by means of the connective tissue strands above referred to. This may be more clearly seen in the two sections preceding the one from which figure 10a, was drawn, in which only a portion of the chorda! sheath surrounded by parallel strands of connective tissue may be seen, upper portion of figure. In the retropharyngeal region cephalad to the pharyngeal bursa the notochord is present in the form of three relatively large clumps of chordal tissue, the most anterior of which, just before the chorda again bends dorsally, touches the pharyngeal epithelium which is here also slightly evaginated. The chorda ends in the basioccipital near the hypophysis anlage, and in its course from the retropharyngeal region to its termination, consists of a continuous chord of chordal cells sursounded by a well developed chordal sheath. The craniopharyngeal canal is practically' obliterated, although the place of origin of the hypophysis from the oral epithelium is still evident, and in the mucosa just above this a relatively large mass of hypophysial tissue is found, still attached to the oral epithelium.




Fig. 7 No. (), Hubcr collection, Embn-o (7, 16 mm. Reconstructed outline drawing of midplace sajiittal .section of head. Xotochord black. X 7.5.

Fig. 7 No. 6. Huber collection, Embryo G, 16 mm. Drawing shows portion of vault of jiharynx and dorsum of the tongue. Distinct, bilobed ventral extension of the notochord, just dorsal to the thyroglossal pit in tongue, which does not quite reach the pharyngeal epithelium, which is neither distincth- thickened nor pitted in this region. X 100.

Fig. 8 No. 32, Huber collection, Embryo H, 19 mm. Reconstructed outline drawing of midplane sagittal section of head. Xotochord black. X 7.

Fig. 8a No. 32, Huber collection, Embr\-o H, 19 mm. Drawing shows a portion of vault of pharynx, the anlage of a pharj-ngeal bursa, and two ventral extensions of the notochord the more slender of which is in contact with the pharyngeal epithelium of the bursa. X 100.

Fig. 9 No. 33, Huber collection, Embryo /, 25 mm. Reconstructed outline drawing of midplane sagittal section of head. X'^otochord black. X 7.

Fig. 9a No. 33, Huber collection, Embryo /, 25 mm. Drawling shows a portion cf the pharj-ngeal vault including the ventral part of the basioccipital in stage of embryonic cartilage. A distinct, slender pharyngeal bursa. The notochord, ventral to the cartilage — right end of figure — comes in contact with blind end of bursa. Xotochord cut twice to the left of bursa, as seen in figure. X 100.



Embryo K, Huber collection. No. 49, 47 mm. Well preserved embryo. Basioccipital shows early stages of bone development. Nearly the entire head chorda has disappeared. The original course through the caudal end of the basioccipital can l^e traced by a band of homogeneous matrix free from cartilage cells. No trace of notochord in tlie retropharyngeal region. There is present a shallow, but well developed pharyngeal bursa, to which m.ay be traced strands of dense fibrous tissue, coming from that region of the basioccipital which contained the place of exit of the notochord in its course into the retropharyngeal region. A portion of the cephalic end of the notochord, having the form of a Y, is found in the ])asioccii)ital near the region of the hypophysis. The larger arm of thi^ F-shaped structure points ventrally toward the retropharyngeal region, one of the shorter arms toward the hypoph^'sis, the other reaches the dorsal perichondrium a little caudal to the sella turcica.


Embryo L, Huber collection, No. 23, 60 mm. Figure 11 and figure 11a. The sagittal series embraces that portion of the eml)ryo extending from the base of the skull to the diaphragm, cut in sections of 15/i thickness. Tissue well preserved. Early stages of bone development in the caudal end of the basioccipital. A large irregularly slKiped mass of chordal tissue is found just cephalad of the dens epistrophei and dorsal to the caudal end of the basioccipital. The course of the chordal canal through the caudal end of the occipital cartilage is evident, but no chordal tissue is met witii until the x-ciitfal siii-|':icr of the caflilaK*' is reached. There is a small mass of choidal epithelium emlieiMed in the pei-iehon(h"ium. Dorsal and sliiihtly caudal to a well de\-elo|)ed ph:uynse«il l)ursa ther(^ is ohserxcd a large, irregularly sha|)ed mass of chordal tissue, which though not in contact witii the epithelium of the pharyngeal bursa, is attaeh(>(l to the Mind end of the Imrsa !)>' means of strands of fiVu'ous connective tissue, as shown in figure 11a. This chordal mass presents a slender ventrally projecting portion which in other sections of the series may be traced to nearly the pharyngeal jjursa. The retropharyngeal region contains three otluM- ridativeh' large masses of chordal tissue, which, howevei-, do not come in contact with the pharyngeal epithelium. The cephalic end of the notochord ends in the basioccipital some little distance from the sella turcica. The general relations of the chordal remains in the retropharyngeal region are shown in figure 11.


Embryo M, Huber collection No. 27, 100 mm. Figure 12. That portion of this embryo extending from the base of the skull to the diaphragm cut in sagittal sections of lo/j. thickness. Tissue well preserved. Caudal end of Ijasioccipital in stage of endochondral bone development, center of ossification of the body of the sphenoid indicated. Practically the entire head chorda has disappeared. There is observed a relatively large mas-^ of chordal tissue lying dorsal to the caudal end of the basioccipital, as shown in figure 12. The retropharyngeal region is free from chordal remains with the exception of a small mass lying against the perichondrium in the region where in earlier stages the chorda turned dorsail}" to reenter the basioccipital, just dorsal to this, several detached masses of chordal tissue are found in the cartilage some little distance from the sella turcica. There is found a very shallow depression of the pharyngeal wall which from its position and its relation to the upper border of the pharjmgeal constrictor muscles must l^e looked upon as an imperfectly developed pharyngeal bursa. Toward this slight depression there extends a band of denser connective tissue which has its origin in the periosteum near the caudal end of the basioccipital, a band which Froriep has designated as the Lig. occipito-pharyngeum. In the mucosa ventral to the cartilage beneath the sella turcica there is found a relatively large mass of hypophysial tissue of cylindrical shape, and still attached to the lining epithelium.


Embryo X, Huber collection. Xo. 29, 135 mm. Figure 13. That portion of this embryo extending from the base of the skull to the thyroid I'egion in the neck cut in sagittal sections of 20,u thickness; slightly macerated, the epithelium in part attached. The greater part of the basioccipital shows endochondral and periosteal bone development; the body of the sphenoid shows endochondral bone. All traces of the head chorda have disappeared with the exception perhaps of a remnant situated in a relatively large space in the cartilage, slightly caudal to the sella turcica. This embryo presents a well developed pharyngeal bursa situated just cephalad to the upper border of the pharyngeal constrictor muscles. Its relations are shown in figure 13. The epithelium lining the bursa is stratified and presents especially on its posterior wall patches of stratified ciliated columnar epithelium interspersed in the stratified pavement epithelium. The connective tissue surrounding the bursa contains many nuclei, not arranged, however, to form an adenoid tissue.

 

Fig. 10 No. 47, Huber collection, Embryo /, 32 mm. Reconstructed outline drawing of midplane sagittal section of head. Notochordal remains black. Distinct pharyngeal bursa just cephalad to the upper JDordor of the pharyngeal constrictors. X 5.

Fig. 11 No. 23, Huber collection. Embryo L, 60^mm. Reconstructed outline drawing of midplane sagittal section of portion of head. Xotochordal remains black. Deep pharj-ngeal bursa situated just cephalad of the upper boi'der of pharyngeal constrictors. X 5.


Fig. 10a No. 47, Huber collection, Embryo ./, 32 mm. Drawing shows the deep pharyngeal bursa and surrounding retropharyngeal mucosa. Upper portion of figure shows a thickened chordal sheath accompanied by parallel strands of fibrous tissue, reaching the blind end of the bursa. X 100.

Fig. 11a No. 23, Huber collection. Embryo L, 60 mm. Drawing shows vault of pharynx in region of the pharyngeal bursa. Large mass of notochordal tissue dorsal to bursa and united to bursa by strands of fibrous tissue having a parallel course. Smaller mass of chordal tissue, h'ing near pharyngeal epithelium, to the left in figure. X 100.



Embryo O, Huber collection. No. 30, 145 mm. Figure 14 and figure 14a. That portion of the embryo extending from the base of the skull to the thyroid region in the neck cut in sagittal sections of 15/i in thickness; slightly macerated, epithelium in ])art detached. Ossification about as in Embryo .V, except that it is further advanced in the body of the sphenoid. ISIo traces of head chorda present. The mucosa ventral to the sella turcica contains a relatively large mass of hypophysial tissue which is arranged in epithelial cords and closed vesicles. There is present a well developed pharyngeal ])ursa situated just cephalad of the upper ])order of the pharyngeal constrictor muscles, as is shown in figure 14. The epithelium lining the liursa is stratified, its posterior wall showing patches of stratified ciliated columnar epithelium interspersed between areas of stratified pavement epithelium. The blind end of the pharyngeal bursa is slightly invaginated by a well defined mass of adenoid tissue, the anlage of the pharyngeal tonsil. In figure 14a is shown the upi^er end of the bursa with the contiguous adenoid tissue. Attention should be called to the fact that the posterior wall of the l^ursa is directed to the left in figure 14a, the reverse of that shown in figure 14.


By way of comparison and to emphasize the fact that it is necessary to have at one's disposal human embryos in order to study in detail special structures in their development in man, I present here reconstruction drawings of the heads of rabbit, pig and rat embryos of a stage in which the vertebral anlagen and the basioccipital present the structures of embryonic cartilage, and in which the head chorda may be traced throughout its entire extent.


Rabbit embryo, Series L. Emb. coll. Depart. Hist, and Emb., U. of M., 17 mm. crown-rump length, fi :ure 15. Vertebral anlagen and basioccipi tal in the stage of embryonic cartilage. Oral portion of hypophysis still attached to the chordal epithelium by a cord of cells. Slightly caudal to this oral attachment of the hypophysis a distinct evagination of epithelium, which for the present I may regard as the remains of Seessel's pocket. The notochord passes in a tortuous course from the t\p of tlie dens epistrophei to the dorsal surface of the caudal (>nd of the basioccipital, then passes obliquel}^ through this to reach the ventral surface of the


cart ilaiif hct w frii w hicli and t he dciiM' pciirlmiidii iim il ('(dirscs to near its cephalic ciid. It then tuiais dorsally, rcciitci-iii^- the hasioccipit al carlilajiic to tcnuiiiatc in contact with the pcrichoiuhiuiu iiiiiii};' th(! posterior wail ot" tlie sella turcica. Nowhere does the iiotochord reach the retrophaiA'ii.ueal tissue \-enlral to the peiiclioiKh'iuiu of the liasioccipital.

Pill cnihrt/o. Xo. •), JmuI). coll. Depart. Hist, and J'Jul). T. of jM., 20 nun. ci-owii-iinup leiiiith, figure Hi. \'ertel)i'al aiilage and l)asiocci])ital in stafil' of enihrxonic cai'tilajiie. Hyi)ophysis just after coni])lete se])aration from oral ei)it helium. The notochord after passing thr(nij.;h dens epistrophei passes to the dorsum of the caudal end of the hasioccipital, into which it passes ol)li(]uely, descending to about the middle of the cartilage and jire.senting a tjrtuous course. About midway between the caudal and the cephalic end of the basioccipital the notochord approaches the ventral side of the cartilage, however, is surrounded on all sides by cartilage. From here the notochord bends dorsall}?" in a long curve, to terminate under the perichondrium of the posterior wall of the sella turcica. In the pig embryo of 30 mm. head-rump length used b}^ JVIead in his study of the chondrocranium, the notochord reached the retropharjmgeal region and was interrupted by infoldings of the pharyngeal epithelium. Mrs. Gage states that in about 20 per cent of pig embryos studied by her, the notochord came in contact with a mouth pocket similar to that found in man. None of the embryos of my series of pertinent stages, though the series is not extensive, show this, but present about the relations of the head chorda shown in figure 16.

Rat embryo. No. 9, Emb. coll. Depart. Hist, and Emb. U. of IM., 9 mm. crown-rump length, figure 17. Vertebral anlagen and basioccipital in stage of embryonic cartilage, though the cells are beginning to be separated by matrix. H^pophj^sis just after complete separation from oral epithehum. Just caudal to the place of attachment of the oral portion of the h\T)ophysis, still evident in the series, there is observed a distinct evagination of the lining epithelium, which for the present may be regarded as the remains of Seessel's pocket. The notochord after leaving the dens epistrophei passes to the dorsal surface of the caudal end of the basioccipital, and then extends cephalad along its dorsal surface just beneath the perichondrium, and in part embedded in the perichondrium, to near the caudal border of the sella turcica. At no place is the notochord embedded in the cartilage of the basioccipital. This is the usual course of the head chorda in the series of rat embryos -at m}^ disposal. It is evident, therefore, that in the three forms here presented, with possible exception in pig embryos, the head chorda has a course which is very different from that noted in human embryos, and furthermore that its course is characteristic in each of the forms presented; in rabbit embryos, along the ventral surface of the cartilage of the basioccipital, in pig embryos, again with possible exceptions, through about the middle of the cartilage of the basioccipital, and in rat embryos along the dorsal surface of the basioccipital. Any attempt to draw deductions as to the relations of the head chorda in man based on observations made on the mammalian embryos noted, therefore, would be futile and misleading.


Fig. 12 No. 28, Huber collection, Embiyo .1/, 100 mm. Reconstructed outline drawing of midplane sagittal section of portion of head. Notochordal remains black, dorsal to caudal' end of the basioccipital. Shallow pharyngeal bursa just cephalad of upper border of pharyngeal constrictors. Distinct Lig. occipitopharyngeum of Froriep. X 4.

Fig. 13 No. 29, Huber collection, Embryo A', 135 mm. Reconstructed outline drawing of midplane sagittal section of portion of head. Distinct pharyngeal bursa situated just cephalad of the upper border of the pharyngeal constrictors. X 2.

Fig. 14 No. 30, iluber collection, Embryo 0, l-lo mm. Reconstructed outline drawing of midplane sagittal section of portion of head. Distinct pharyngeal bursa, with anlage of the pharjmgeal tonsil, situated just cephalad of the upper border of the pharyngeal constrictors. X 2.

Fig. l4a No. 30, Huber collection. Embryo 0, 145 mm. Drawing shows the dorsal part of the pharj-ngeal bursa with the anlage of the pharyngeal tonsil. X 100.

Fig. 15 Rabbit embryo, crown-rump length 17 mm. Reconstructed outline drawing of midplane sagittal section of head. Xotochord black, hypophysis still attached to epithelium. X 7.5.

Fig. 16 Pig embryo, crown-rump length 20 mm. Reconstructed outline drawing of midplane sagittal section of head. Notochord black. X 7.5.

Fig. 17 Rat embryo, crown-rump length 9 mm. Reconstructed outline drawing of midplane sagittal section of head. Xotochord black. X 7.5.


The material presented, it seems to me, shows conclusively that there exists in human embryos a distinct relation between the head notochord and the pharjmgeal entoderm in the devplojDment of the pharyngeal bursa, as was first demonstrated by Froriep, confirmed by Nebelthau, Mrs. Gage, Meyer, Linck. In the earlier stages of development of the human embryo, in embryos having head breech length of from 5 mm. to 8 mm., a time when the head chorda is separating distinctly from the pharyngeal entoderm, one may determine a small area in which the notochord remains in close contact with the pharyngeal entodemi, in which area the pharyngeal epithelium shows a distinct reaction evinced by an increased thickness of its cells. This area is situated, in the stages under discussion, some distance caudal to the region of the thjToglossal pit in the tongue, although the distance between the points varies somewhat in different eml^r^^os. This area of contact of chordal and pharyngeal epithelium is found at the end of the ventral flexure of the notochord as this bends ventrally to pass from the vertebral anlagen to the retropharyngeal region. If several points of contact are noted, as is often the case in these earlier stages, the special area above mentioned is the most caudal and is constant both as to character and position, and represents, I am convinced, the seat of the development, of the pharyngeal bursa. This area is separated from the region of Rathke's pouch and Seessel's pocket by practically the whole length of the future pharyngeal vault, as is clearly shown in Embryo A, of this series (fig. 1). The contention of Meyer that the pharyngeal bursa develops from the region of Seessel's pocket is not confirmed, therefore, l)y my own ohscrxat ions. In Inininn cinhryos liaxinj!; a (M'own-brcccli Icn^tli of tVoin S nun. to IT) nnn., spiinnin^ :\ pci-iod iu Nvhicli the (1(mis(> nu'scMicliyme of the voutral iiulaj2;('n and llio basi()('cii)it;il (l(>\(>lo|)s to the stage of precartilage or embryonic cartilage, niul in wliich the notochord becomes distinctly separated from tlu' pharyngeal e|)itlielinm in the retropharyngeal region by ingrowtli of niesenehyme, the notochord i)resents a distinct loop just C(>])halad of the ventral flexure by means of which it passes from the xcrtebral anlagen to the retrophar3'ngeal region \-entral to the basioccipital. This loop of the chorda, always distinct, is situated a little caudal to the region of the thyTogiossal pit in the tongue, for the earlier stages, and just about dorsal to this pit for the older stages of the human embryos varying in length of from S mm. to 15 mm. showing that the area of distinct contact of choi-dal and i3haryngeal epithelium, the area where the pharyngeal bursa develops, changes it relative position as the embryo proceeds in development. In one of the embryos of my series, Embryo F, this ventral loop of the notochord has already separated from the phary^ngeal epithelium indicating a looser connection between chordal and pharyngeal epithelium than in other embrj^os in which this connection j^ersists in.to older stages. All observers who have studied the development of the embryonic pharj^ngeal bursa state that this is not present in all embryos. The percentage of embryos in which the embryonic pharyngeal bursa is present or absent, as given by these different observers, varies. The data given are not comparable, since embryos of different ages or lengths are used by the several observers dealing with this question. SufHce it to say that all observers who have especially studied the development of the pharyngeal bursa have noted its absence in a certain percentage of embrj^os studied. It is, therefore, of interest to note that the connection between notochord and phary^igeal epithelium may be so loose in certain embryos that a comj^lete separation is attained in early stages, as in Embryo F, 13 nnn., the ingrowth of the mesenchyme into the retrophar^^lgeal region being sufficient to completely separate the chorda from the pharyngeal epithelium. In my^ series of human embryos having a length varying from 15 mm, to about 30 mm there was present a distinct embryonic pharyngeal bursa in all except Embryo G, and in all except this embryo did the ventral extension of the notochord come in close relation or in direct contact with the epithelium of the blind en.d of the pharyngeal bursa. In Embryo G, there is present a distinct bilobed ventral extension of the notochord, situated just dorsal to the thyroglossal pit of the tongue, the region of contact of the chordal and pharyngeal epithelium in case a pharyngeal bursa develops, which, however, was lacking in this embryo, neither was the pharyngeal epithelium of the region thickened. This embrj^o I interpret as again showing an early separation of head chorda and pharyngeal epithelium, owing to a loose connection between the two structures. Of the older stages presented all but Embryo M show a distinct phar^mgeal bursa. In this embryo in which there was present a shallow depression, which may be regarded as an imperfectly developed pharyngeal bursa, in that it is situated just cephalad to the upper border of the pharyngeal constrictors, a relation characteristic for older stages, there is present a distinct occipito-pharyngeal ligament, which ligament w^as regarded by Froriep as a possible caustive factor in the development of the phar\aigeal bursa. The fact that in this embryo there is present only an imperfectly developed pharyngeal bursa on the one hand and on the other hand an especially well developed occipito]:>haryngeal ligament, would seem to argue against regarding this ligament as a causative factor in the development of the pharjaigeal bursa. In the older stages presented, the head chorda is in process of disintegration, or has entirely disappeared from the retropharyngeal region. In those embryos in which chordal remains are present in the retropharyngeal region a close relation between such chordal remains and the pharyngeal bursa was noted. Embryo has been added to show that the pharj^ngeal tonsil develops in connection with the pharyngeal bursa, if such bursa is present, and that the development of the pharyngeal bursa is independent of that of the pharyngeal tonsil, and not as Schwabach maintained, due to the development of the tonsil. Froriep and especially Linck have discussed the nature of the influence exerted by the notochortl on the de\^elopment of the pharyngeal bursa. n'^ni'diiit!, it,> actum as lai-ucly iiiccliaiiical. l.iiick discusses this pliasc (»!' t h(M|iicsti(»ii at some Iciiiitli. The constant relation of tlic notocliord to the phaiyiiiical c])it hchiiiii, after the chorda bej»;ins to s(»])ai-at(> fi-om ihe epithchuiii, the (h^liiiite location of this area of contact, and the distinct reaction of the phaiyiif^eal entode]-ni at the scat of contact leads nie to rej^ard this relation of chordal and phai'vniitvd e])ithelinin other than an accidental one, and that thus to some extent the pharyngeal bursa may be regai'ded as a structure sui (/ciicris. In the early stages showing the anlage of the pharyngeal bursa the e])itheliuni is distinctly thickened in tlie region of the future bursa, showing cell proliferation, although mitosis was not evident in my preparations. That a close connection between chordal and pharyngeal epithelium is necessary to the development of the phar^-ngeal bursa seems evident from the preparations of my series which show that the anlage of the bursa is present only when this connection between chordal and pharyngeal epithelium is maintained after the remainder of the notochord in the retropharyngeal region is separated from the pharjaigeal epithelium. If in early stages of development, human embryos of from 10 mm. to 15 nmi., crown breech length, this connection is so loose as to lead to a separation of the notochord from the pharyngeal epithelium throughout the entire retrophar3^lgeal region, no pharyngeal bursa develops. It is of interest to note finally that in the pig there is found a phan^lgeal pocket which has been considered as the homologue of the pharyngeal bursa as found in man. Whether this pharyngeal pocket is a constant structure in the pig I am not prepared to say. ]Mrs. Gage and ]Mead have shown that in a certain per cent of pig embryos the head notochord reaches the retrophar^nigeal region and comes in contact with the epithelium of the pharyngeal vault. From Killian's comprehensive comparative studies we learn that a pharyngeal bursa, such as is found in man, is very rare, indeed found only in Arctomys marmota. In the mammals, the embryos of which are more generally accessible for laboratory work, only the pig has a pharAaigeal bursa or its homologue, and only in pig embrj^os does the head notochord reach the retropharyngeal region and come in contact with the pharj^ngeal epithelium.

==Literature Cited==

DuRSY, E. 1869 Zur Entwicklungsgeschichte dcs Kopfes des Menschen und der hoheren Wirbelthiere. Tubingen. 

Froriep, a. 1882 Kopftheil der Chorda dorsalis bei menschlichen Embryonen. Als Festgabe flir Jacob Henle, Bonn. 

Gage, Susanna Phelps 1906 The notochord of the head in human embryos of the third to the twelfth week, and comparisons with other vertebrates. Science, New Series, vol. 24. 

Gaup, E. 1906 Die Entwickelung des Kopfskelettes. Hertwig's Handbuch der vergl. u. exper. Entwickelungslehre der Wirbeltiere. Bd. 3, Zweiter Teil. 

GopPERT, E. 1906 Die Entwickelung des Mundes, der Mundhohle and ihrer Organe. Hertwig's Handbuch der vergl. u. exper. Entwickelungslehre der Wirbelthiere. Bd. 2, Erster Teil, 1906. 

Grxjnwald, L. 1910 Eine Cyste der Chordascheide. Anat. Anz. Bd. 37. 

Killian, G. 1888 Ueber die Bursa und Tonsilla pharyngea. Moroh. Jahrb. Bd. 14. 

KoLLiKER, A. 1879 Entwicklungsgeschichte des Menschen und der hoheren Thiere. Engelmann, Leipzig. 

LiNCK, A. 1911a Beitrag zur Kenntnis der menschlichen Chorda dorsalis im Hals und Kopfskelet. Anat. Hefte, Bd. 42.

1911b Ueber die Genese der Bursa phnryngea embryonalis. Zeitsch. f. Ohrenheilkunde. Bd. 62. 

Levi, Giuseppe 1900 Beitrag zum Studium der Entwickelung des knorpeligen Primordialcraniums des Menschen. Arch. f. Mik. Anat. Bd. 55. 

LusHKA, H. v. 1860 Der Hirnanhang und die Steissdriise des Menschen, Berlin.

1868 Der Schlundkopf des Menschen. Tubingen. 

Mayer, A. F. C. J. 1840 Bursa sen cystis tubae Eustachianae bei einigen Saugethieren. Neue Notizen aus dem Gebiete der Natur- und Heil kunde von Froriep. Bd. 14.

1842 Neue Untersuchungen aus dem Gebiete der Anatomic und Physiologic. Bonn. 

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Mead, C. S. 1909 The chondrocranium of an embryo pig, Sus scrofa. Am. Jour. Anat. vol. 9. 

Meyer, R. 1910 Ueber die Bildung des Recessus pharyngeus medius s. Bursa pharyngea im Zusammenhang mit der Chorda bei menschlichen Embryonen. Anat. Anz., Bd. 37. 

{{Ref-Minot1907}}

Minot, Charles S. 1907 Segmental flexures of the notochord. Anat. Rec, no. 3. 

Nebelthau, 1895 Ueber die Gallertgeschwulste am Clivus Blumenbachii. Inaug. Disser, Marburg (quoted from Linck). 

Oppel, A. 1900 Lehrbuch der vergleichenden mikroskoi>ischen Anatomie der Wirbeltiere, Drifter Theil, P^ischer, Jena. 

Schwabach, 1887 Ueber die Bursa pharyngea. Arch. f. Mik. Anat., Bd. 29.

1888 Zur Entwickelung der Rachentonsille. Arcli. f. Mik. Anat., Bd. 32. 

Williams, L. VV. 1908 The latci- (icvcl(ii)mcn( of llic notocliDrd in mammals. Am. Jour. Anat., vol. 8.

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