1897 Human Embryology 19

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Minot CS. Human Embryology. (1897) London: The Macmillan Company.

Human Embryology: Introduction | The Uterus | General Outline of Human Development | The Genital Products | History of the Genoblasts and the Theory of Sex | The Germ-Layers | Segmentation | Primitive Streak | Mesoderm and the Coelom | Germ-Layers General Remarks | The Embryo | The Medullary Groove, Notochord and Neurenteric Canals | Coelom Divisions; Mesenchyma Origin | Blood, Blood-Vessels and Heart Origin | Urogenital System Origin | The Archenteron and the Gill Clefts | Germinal Area, the Embryo and its Appendages | The Foetal Appendages | Chorion | Amnion and Proamnion | The Yolk Sack, Allantois and Umbilical Cord | Placenta | The Foetus | Growth and External Development Embryo and Foetus | Mesenchymal Tissues | Skeleton and Limbs | Muscular System | Splanchnocoele and Diaphragm | Urogenital System | Transformations of the Heart and Blood-Vessels | The Epidermal System | Mouth Cavity and Face | The Nervous System | Sense Organs | Entodermal Canal | Figures | References | Embryology History

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Chapter XIX. The Mesenchymal Tissues

As the numerous tissues which result from the differentiation of the mesenchyma enter to a greater or less extent into the formation of the organs of which the main parts are derived from the ectoderm, entoderm, or mesothelium, it is desirable to begin the study of the organs with a general review of the mesenchyma. The development of the skeleton is treated in the next chapter, p. 422.

Classification of Mesenchymal Tissues. — The fundamental and essential characteristic of the mesenchyma is, that the cells are some distance apart, but connected together by their own protoplasmatic processes. The tissue is made up of anastomosing cells. The spaces left between the cells are filled with intercellular substancey which, owing to the size of the spaces, constitutes a large part of the tissue. In £is respect the mesenchyma offers a marked contrast to all cpithelia, for the latter have the intercellular substance reduced to a minimum. The intercellular substance is an extremely important factor in the differentiation of the mesenchymal tissues; in fact so important that it affords a better basis for the classification of the tissues than the cells themselves. To these fimdamental conceptions I attribute a great value.

In the primitive stage we have cells with small protoplasmatic bodies, connected by few processes and imbedded in a homogeneous matrix (intercellular substance) . We can distinguish in subsequent changes three main sets of modifications: 1, those which are specially characterized by changes in the basal substance; 2, those characterized chiefly by changes in the cells ; 3, those characterized by the special arrangement of the tissues produced by the differentiations of the mesenchyma.

In the first series I put the development of connective-tissue fibrils and fibres, of the intercellular network both elastic and non-elastic, of mucin, as in Wharton's jelly, of cartilage (chondrification), of bone (ossification), and also the disappearance (or liquefaction?) of the basal substance, and finally its hypertrophy.

In the second series I put the development of the blood-vessels, of the lymphatic vessels, muscle-cells, fat-cells, pigment-cells, and of the marrow of bones.

In the third series I put the development of the connective- tissue cavities such as the s}Tiovial, bursal, and subarachnoid, and the formation of special layers such as the subepithelial basement membranes, the submucosa, the cutis, and so forth. What little there is to be Siiid in regard to the special layers will be found in connection with the histor}' of the special organs of which they form parts.

The foll(3wing table gives the classification adopted. It must be borne in mind that the classification is somewhat arbitrary, since in all the tissues modifications occur in both the cells and the intercellular substance; moreover, several differentiations may occur simultaneously or successively in the same part; for instance, the fibrillsB and network are usually found together; cartilage mayor may not have fibrill» and elastic tissue.

Mesenchymal Tissues.

First Series. Second Series. Third Series.

(Changes in matrix). (Changes in Cells.) (Spocial arrangements).

1. Fibrils. 1. Blood vessels. 1. Cavities.

2. Network. 2. Iymphatics. a. synovial.

a. vellow elastic. 3. Miuscle- cells. h. bursal.

b. white non -elastic. 4. Fat-cells. c. subarachnoid. 8. Mucin. 5. Pigment-cells. 2. Membnuies.

4. Chondrification. 0. Marrow. a. baseinent.

5. Ossification. b. submucous.

6. Disappearance. c. dermal.

? by li(iuefa<*tion. etc.

7. Hypertrophy. 3. Ligiiments.

4. Tendons.

Embryonic Mesenchyma. — Concerning the very early history of the mesenchjTna we have little satisfactory knowledge l)eyond the fact that the cells of the masoderm are at first closely crowded and as they move apart are seen to remain connected together by protoplasmatic processes.


As regiirds the shape of the cells I distinguish two stages, of which the earlier has not hitherto been definitely recognized. In the first stage, which I have observed t(^ occur to elasmobranchs, birds, imd mammals, the protoj)lasin fonns a complex network in which the nuclei are scattered at irregular intervals ; around the nuclei th^o is often little or no condensation of protoplasm, no that there are, projjerly speaking, no perinuclear cell bodies. The tissue corresponds, therefore, very poorly to our conventional conceptions. This stage is well represented by the mesoderm of the umbilical cord in a human embryo of about seven weeks. Fig. 2()r», j). 35S. The form of the cells — or, if the expression bo prcfenvd, of the n«»desof the reticulum — varies greatly, but in a definite manner in the various regions of the embryo; the variations depend cliiefiy upon the densitv of the tissue and its trend: for instance, in amnioto embrvos with two to four gill-clefts there is jd ways a distinct contrast between the dennal mesenchvma, which is of loose texture and with no decided trend, and the mesenchyma l)etween the muscle-plate and the me<hillary tube, which is dense and has elongat(Ml cells. The differences have never been comprehensively studied, and we can only say that they are the expression of unliktM'onditions of origin and growth of the various parts of the mes^Michyma. In the srennd stage, which seems to l)e reached bv all the cells of the mesenchvma S(K)ner or later in all vertebrates, the protoplasm has formed distinct cellbodies around the nuclei, imd there are no con si (b arable aecimmlations of protoplasm except anmnd the nuclei. This stagt^ is illusrated by the human umbilical cord at three months. Fig. '107, p. o')!*, and is still more typicidly and characteristically shown by the mesoderm of a chick of the third or fourth day, or in a rabbit embryo of ten or eleven days; in the dog-fish this stage is not reached until considerably later in the development than in the amniote embryo. In the chick, Fig. 234, the cells have a large nucleus of roimded form, with a distinct intranuclear reticulum of protoplasm and one or several granules of chromatin; the nucleus is surrounded by granular protoplasm, constituting a small cell-body, which sends off tapering processes to unite with similar processes of other cells ; the processes are sometimes very short, but vary in length up to two or three times the diameter of the cell-bodies. The length of the processes also varies th

in different retrions, so that the nucleus in karyoklneais; the chromatin loops 11 . • _. are seen in cross-section.

cells in one region are more or less crowded than in others; the cells also vary in shape, being elongated in certain districts ; the^se differences are all significant as the results of previous development and as establishing conditions for the subsequent development. In young mammalian embryos the cell-bodies are less well marked than in the chick, and the processes form a network of fine threads between the cells, as can be seen in places in rabbit embryos, as late at least as the seventeenth day.


The matrix is perfectly clear, homogeneous, colorless, and structureless ; it is of slight consistency, and scarcely stains with any of the most used histological dyes.


Intercellular Differentiation. — The means by which differentiation of the mesenchymal matrix is effected are little understood. If we accept the view, which is, however, as yet by no means beyond doubt, that the fibrils and network arise from the cells, we can account for a part, but only for a part, of the intercellular structures. If, on the other hand, wo hold that all intercellular structures are of intercellular origin, then wo can assume that there is some general principle in accordance with which they are all produced. Even in this case the cells must have some influence, since their presence and vitality are essential conditions.


Experiments published by Harting are suggestive in this connection.


Connective-Tissue Fibrils. — The fine fibrils of the adult connective tissue appear quite eaily in the embryo in the intercellular substance. There are two theories of the origin of the fibrils: 1, they arise from cells; 2, they arise from the matrix. Their origin from colls was the view of the founder of the modem cell theory, Theodore Schwann, 39.1, who thought that the cells grew in length and split into bundles of fibrils. Various modifications of this theory have since appeared; thus Obersteiner (Sitzungsber. Wien. Akad., LVI., '^ol) traces the fibrillsB to outgrowth of spindle-shaped mesenchymal cells. Max Schultze (Reichert's Archie, 1801, 13) thought that the cells fused together and their fused parts formed the fibrilla? as well as the intercellular substance, thus tracing the fibrillar to a differentiation of the peripheral parts of the colls — a view which, somewhat nio<litie<l, has been revived by B. Lwoff, 88.1, who maintains that the fibrilUe arise from the surface of the cells, nearly the whole body of each cell being converted into fibrillre, which extend along whole rows of cells and along their processes, enveloping the protoplaam. The origin of the fibrils by deposition in the matrix was first maintained by Henlo ("' Allgemeine Anatomie," Erste Auf]., 'd7'.*) and was, in my judgment, demonstrated by BoUet's investigatiuns, recorded in Strieker's "Qewebelehre," 1871, 62-(ir, upon the omentum, and by Ranvier's later observations ("' Traito technique d'Histologie,"40fM:ll). Kolliker, whoso judgments upon histological problems are rarely mistaken, has accepted in his "Qewebelehre," tlto AuH., 1211, the intercellular origin of the fibrils. If we examine a tissue in which the fibrils are just beginning to appear, as, for inatjinoe, the human umbilical cord toward the end of the third month. Fig. 207, p. 35!', or the omentum of a sheep embryo of 17 cm., we find the fibrils running singly and in everj' direction, both ])arallel with the cells and their pn>ces8es and at all augles with them. The omentum, as pointed out by Rollet, is a particularly favorable object, for we are sure of having the entire length of the fibres. The ceWii of tho omentum gradually assume (sheep embryos 4-7 cm.) an elongated spindle form, remaining connecteti together only by very few processes, which arise chiefly from the end of (t the cells; the nuclei become oval, and when stained with hsematoxylin have a distinct membrane, and consist of a clear outer layer and a dark granular central part. Between the cells, and for the most part remote from them, appear the fibrils, which grow in length jmd number. In later .-it a gen, Fig. ••■■ir,. the ci'iis of the (Hneiitiini lire more attenuated, and their ends ai-e unite)! ho as to fonn a network, though some of the cells appear to terminate without iiiiy connection with their fellows; the nuclei m-e more finely ■^i-junilur and have lost the clear outer zone, chanicteristie of earlier wtages. the fibrillar have grown in length and increased enormously in number; they form bundles which take a wavy course ; these bundles frequently subdivide and unite, so that they form a network; their course and arrangement are independent of the trend of the cells, and there is nothing to suggest any genetic connection between the cells and the bundles of fibrils. Scattered about there are also usually a few leucocytes. Fig. 235, leUy which are readily distinguishable from the true mesenchjTnal cells or so-called connective-tissue corpuscles, c c. The bimdles of fibrils correspond to the connective'tissue ^ fibres'^ of the adult; each fibre consiste of a large number of fibrils. The embryonic fibrils differ from those of the adult in staining much more readily. The growth of the fibres depends upon multiplication of the fibrils for Harting (" Recherches micrometriques sur le developpenient des Tissus," etc., 1845, p. 63) found that the fibrils measured 0.0010-0.0014 mm. in the foetus and from 0.0007-0.0017 mm. in the adult ; as, therefore, the fibrils do not thicken they must increase in number as the bundles or fibres enlarge.


Ranvier, /.c, finds that the fibrillae have no connection with the colls in three tissues, which he has studied in regard to this point, namely, the embrj^onic dermis, the developing tendon, and the sclerotic cartilage of rays. E. A. Schafer (Quain's "Anatomy," nintli edition, II., 72) writes as follows: "The view which supposes that a direct conversion of the protoplasm of the connective-tissue cells takes place into fibres, both white and elastic, has of late years been widely adopted, but it seems to rest less upon observation than upon a desire to interpret the facts in accordance with the conceptions of Beale and il. Scliultze, according to which every part of an organized body consists either of protoplasm (formative matter), or of material which has been protoplasm (formed material), and the idea of deposition or change occurring outside the cells in the intercellular substance is excluded. But it is not difficult to show that a formation of fibres may occur in soft substances in the animal organism, independently of the direct agency of cells, although the materials for such formation ma}^ be furnished by cells. Thus in those coelenterate animals in which a low form of connective tissue first makes its appearance, this is distinguished by a total absence of cellular elements, the ground-substance being first developed and fibres becoming formed in it. Again, the fibres of the shell-membrane of the bird's e^^ are certainly not formed by the direct conversion of the protoplasm of the cells which line the oviduct, although it is probably in matter secreted by those cells, and through their agency, that the deposit occurs in a fibrous form."


Intercellular Network or Elastic Tissue. — The intercellular substance of the adult contains in most parts of the mesenchyma a network which varies greatly in appearance. This network has hithero been described usually as being forme<l of elastic fibres; now since the material which forms the network does not always resemble fibres, but often rather lamellae, and since, as shown by F. Mall, 88.3, 91.1, some parts of the network do not contain elastin, it seems very undesirable to continue the use of the term elastic fibres, which is entirely misleading. I shall therefore speak of the two forms of tissue as yellow elastic network and white non-elastic network respectively. Mall states that there is a non-elastic material which alone forms the white network, but which in the yellow network fomriH a sheath around the elastic core.


Concerning the development of the network we possess little accurate knowledge. Just as with regard to the intercellular fibrils, p. 300, there are two theories: according to one, the network arises by metamoqihcjsis of the cells; according to the other, by differentiation <;f the matrix. The origin from ramifying cells was the old the^>ry and sffcnui at first thought plausible — see Donders' remarks in Zeit, wissensch, J?oo/.,III., 358 — for if we assume the cell processes to U* convert<Ml into elastin a network would result. The attempt, however, to demonstrate the actual metamorphosis has hitherto been unsuccessful. Kuskow, 87. 1 , found that in the ligamentum nuchse of tlm <.*mbr>'o, after digestion in cold pepsin solution, the elastic fibres could Ui H(Hm uniting with the elongated mesenchymal nuclei, usually with th(» ends, sometimes with the sides of the nuclei. Heller, whose paiHT I kn(jwonly from the abstract in Hofmann-Schwalte's Ja/ireshertcht for 18H7, 120-127, is s^iid to have seen the connection with nuclei lK>th in the ligamentum nuchaB and in the very young arytenoid cartilage of the embr^^o; in the cartilage of the ear, on the other hand. Heller states that there is no connection of the elastic fibres with eitlu?r the nuclei or the cells. These observations show that the elastic tissue may enter into si)ecial relation to the nuclei, but throwno light on the significance of the connection; we do not yet know wlic;tli(T the fibres develop independently and afterward unite vrith the; nuclei, or are united with them from the start. Kuskow's sugg(»stion that the elastic network is formed by the nuclei is not likely to l)e v<»rifi(Kl, Ixicause nuclei never form outgrowths or unite with oiK' anotluT to make reticubi, so far as heretofore known.


If the connection with the nuclei is secondary, then tlio network may Ik; intercellular in origin.


Hanvier, **Traite technique," 401, 411, has showTi that the elastic tissue; first apjK^ars in the form of rows of granules or minute globulins, ju'obalJy of elastin, which subsequently fuse together into a network tli(!i lines of which are mark(;d out by the original deposition of tho globulins. To form an elastic membrane the globules, instead of iM'iiig arranged in lines, are doposiUnl in small i)atclu»s, and l)y th(»ir fusion form a ])late. In elastic cartilage the granules first make their ai)iM?aranc(;, it is true, in the inimeiiiato neighlx)rh(»d of the cartilage » ('(^Is. This renders it not improbable that the deposition of the granul<»s is influenced by the cells, but docs not prove that they are foruKMl by a direct c'ionvei'sion of the cell -protoplasm. Indeed the substHpK'nt (extension of the fibres into thos(^ parts of the matrix that W(»re ])n»viously clear of them and in which no such dir(»ct conversion of this protoplasm s<H>ms possible is a strong argument in favor of the deiH)sition hv]K)thesis. For an admirable discussion of the two views «v II. Ral)l-Riickhard, 63.1.


As to the time when the elastic fibres appear wo mcay say in general that it is quite late. They appear in the ligamentum nucha) of <*ow embryos of 15 cm.; in the cartilage of the ear in embryos of 30 Uy 32 cm., and human eml)r}'os of five months, Ra])l-Ruckhard, 63.1, 43; in the arytenoid cartilage in cow embryos of .55 cm. ; in adult fibro-ehtstic cjirtilage the eUistic network is still developing, and is not formed at all in the sheaths of nerves until adult life.

The elastic network grows by thickening the fibres and plates, which are found much larger in diameter in the adult than in the foetus. In this respect it forms a striking contrast with the intercellular fibrillaB, which grow princially by multiplication.

Concerning the development of the white non-elastic network we know almost nothing.


Mucous Tissue or Wharton^s Jelly. — In man this tissue occurs only in the umbilical cord. It is characterized by the development of mucin in the intercellular substance. The tissue has already been described, p. 358, and I have only to add that the mucin is present in a diffuse form, and has, so far as yet known, no special structural arrangement. Mucous tissue is said to occur in various parts of the body in fishes, but imless it contains intercellular mucin it cannot be regarded as true mucous tissue, in the sense here considered.


Cartilage. — Cartilage begins to be differentiated earlier than any other of the mesenchymal tissues, except the blood-vessels, which aro developed much earlier, and perhaps the smooth muscle-cells. It is probably older phylogenetically than any of the other tissues of the group except the two mentioned, for not only does it appear very early in the embryo, but is found in invertebrates. It is for convenience only that I consider cartilage after the fibrillse and elastic network, forlx)th of these intercellular structures appear in certain forms of cartilage. In this section the history of cartilage is considered mider the following heads: 1, condensation of the mesenchymal tissue to form the anlage of the cartilage ; 2, appearance of the matrix ; 3, young cartilage; 4, growiih of cartilage; 5, mature cartilage; C, fibrillar cartilage; 7, elastic network cartilage.


1. Condensation of the Tissue. — This takes place simply by the cells becoming very much more closely crowded together than in the surrounding mesoderm; at first merely the central portion of the anlage is thus marked out and there is a very gradual transition to the looser mosench^^ma about; for every piece of cartilage there is a separate anlage, which is distinct from the start ; one exception to this rule occurs in the case of the vertebrae, as has been stated by Gegcnbaur, and has been shown with great precision for birds and mammals by A. Froriep, 83.1, 86. 1. Another exception is offered by cartilages of the limbs of amphibia, which Qoette and H. Strasser, 79. 1, have shown to be coalesced, when they first appear.


As development progresses, the anlage becomes more and more sharply defined until at last its limit can be determined within a cell or two. The cartilage cells are now so crowded that the nuclei, as has been observed in all classes of vertebrates, seem almost to actually touch one another — see H. Strasser, 79.1, 245, and A. Froriep, 86. 1, 73.


When the anlage is completed its peripheral cells become elongated and form the anlage of the perichondrium ; while the central cells, by taking on the rounded form, begin their metamorphosis into cartilage cells; the perichondrium is a thin layer. C. Hasse, 79.1, 2, thinks that the cells assume a spindle shape first, and afterward take on the rounded form, at least in elasmobranchs. It is uncertain whether the two stages can be distinguished in the higher vertebrates. The first cartilaginous anlages appear in the chick during the fifth day, and in the rabbit, I think, about the thirteenth day. The vertebral are probably always the first cartilages to be indicated by completed anlages. The other cartilages bec*ome recognizable later ; the exact times need to be determined by closer study than has yet been attempted.


2. Appearance of the Matrix. — Prce-cart ilage (prochondrium, Torknorpel). — The intercellular substance, as the cells lx?gin to move apart and lose their connections with one another, gradually assumes a greater density and finally tecomes highly retractile and quite resistant mechanically and chemically, and at the same time acquires, at least in many ca^es, a great affinity for carmine and ha?matoxylin. Hasse, 79.2, states that this color-reaction always appears in the young cartilage of elasmobranchs, and therefore he ])rop()ses to distinguish the stage as a distinct one, sinc^e the matrix of the fully differentiated hyaline ca.rtilage docs not stain ; for the j'oung c«irtilage with colorable matrix he proposes the term Vorkiiorpel, which I have Tendevpd prcB'Cartilage. Hasse states that in the pr?p-cartilage of elasmobranchs the matrix consists of numerous fil^rilla? held together by a cementing substance. This is now generally held to be the structure of the matrix in adult hyaline cartilage — see, for instance, Spronck, 87.1, and Kolster, 87.1, who both give refc^rences to the preceding literature. Hasse further states that in i)ne-cartilage the matrix is of uniform structure throughout, and that there are no capsules around the cells. The cells of young cartilage are said to contain glycogen; Rouget claims to have found it in the sheep eml)r\'o at two months. Many authors have held that the matrix was formed as a series of capsules, one around each cell; the cai)sules grow and fuse. In support of this view there are no satisfactory observations knowTi to me. As it is adopted in Quain's "Anatomy" by Schaefer (ninth cnlition, II., 84), I presume it rests uix)n some g(X)d authority, which I have overl(K)ked.


When the condenstnl mesenchyma is l)eginning to change, dark irregular masses appear among the cells ; these are the "prochondral elements" of H. Strasser, 79.1. Alice Johnson, 83.1, 400, states that they may be seen in the hind limb of the chick about the sixth day, and she interprets them as degenerated cells which have lost their nuclei.


3. Young hffaline cartilage differs but little from that just de8cril>eil, except that the matrix has increascnl and the cells are slightly larger. It is to Ix^ considered as the primitive form of tissue, fnwn which all the modifications of adult cartilage tire derivtMl. In th(» thyroid cartilage of a three-months human embryo I find the cells farther apiirt and a little larger than in younger stages; the ct»lls an^ still small and are here and there in grouj)s of two; tin 'v are not round but more or less compressed in shape, and somoof them ap|>ear to contain fcit granules. In the same cartilage at four months the general appearance is the stune as l)efore, but the matrix stains unevenly ; around the cells it is light, but lietwtx^n thi? ci'lls intervenes a darker-colored portion which fonns a network through thi» tissue.


In the neighborhood of the prochondrium the matrix is altogether light and the cells are in part larger, rounder, and with distinct spherical nuclei. In the tracheal cartilage of embryos of about seven months the cells are decidedly larger than those of the thyroid just described; the rounded nuclei are very distinct; the protoplasm is granular and entirely fills the cell space (lacuna) of the matrix ; the cells exhibit only a very slight tendency to form cell groups as in mature cartilage, nor are there any signs I can recognize as such, of the degenerative changes which can be seen in the adult.


4. Growth of Cartilage, — The matrix presumably grows by intussusception, and not, as some authors have maintained, by the continufiil conversion of the superficial protoplasm of the cells into matrix. If such a conversion took place we should expect to see the cells diminish in size, whereas they increase. The cells increase in number by division, and by additions from the perichondrium; of the two factors the latter is probably the more important.


The division of cartilage cells has been especially studied by W. Schleicher, 79. 1. The division is indirect. The nuclear membrane first of all disappears or is converted into filaments which soon become lost among the other filaments developed within the nucleus. The filaments are at first short and irregular, but soon take on a stellate arrangement, and the chromatin becomes grouped into an ecjuatorial plate, which divides, one group of chromatin elements moving toward one pole, the other toward the opposite pole. The division of the protoplasm is not effected as usual in animal cells, but by means of a cell-plate, as in many vegetable tissues; the cell-plate forms a partition in the middle of the elongated binucleate cell ; the plate grows and becomes the matrix between the two daughter cells. As the plate thickens slowly the cells remain near together for some time, and one or both them may again divide with the result that there is a group of three or four cells. This grouping is highly characteristic of adult cartilage, but exactly when it first appears I do not know. It does not appear in embryonic cartilage, so that we must assume either that in the embrj^o the cartilage cells do not divide, or else that they divide and move apart very rapidly. In either case the grouping of the cells remains a sign of age, and ought perhaps to be regarded as the expression of a diminished vitality.


Concerning the exact history of the perichondrial cells as they change into cartilage cells special investigation is needed. At present wo can say hardly more than that the change takes place.


5. Mature Hyaline Cartilage, — The hyaline cartilage of the adult exists in two principal modifications, both characterized by the great development of the matrix and by having the cells for the most part in groups of two, three, or four, but distinguished by having in the one case large cells with round nuclei and well-developed protoplasmatic bodies, and in the other cells which have shrunk somewhat and are often compressed, with nuclei which are often indistinct and irregular, and protojJasm which frequently contains fat globules. I believe that we have to do with two stages in the life-history of cartilage, and that the first modification, in which the cells are large, is the earlier stage, and represents the maximum of development, while the second, in which the cells are shrunk and fatty, represents a later stage, witli more or leas degeneration. Dekhuyzen, whose papers I faiow only through the abstract prepared by himself for HofmannSchwalbe, Juhresbericht f. IHS'J, 82-83, was the first to interpret the mature cartilage as a d^enerating tiesue. In deciding upon the order of the two stages Ihave been guided chiefly by my observations upon the growing cartilages of the hing in rodents, for in them the large, round, protoplasmatic cells lie between the amnective-tisflue cells on the one hand, and thefattj-, compre3sed cartilage cells on the other, and clearly present a transitional stage of the transformation of the perichondrial cell into the old cartilage cell, and by the further oL»icr^'ation that in the child at birth the bronchial cartilage consists entirely of large, rounded cells with spliericiU nuclei. The changes which are here noted as degenerative begin very early; thus Dekhuyzen states that they are well advanced in the epiglottis of the dog at birth.


Little has been done upon the development o( the matrix, but numerous researches have been made uiMin the structure and chemical composition of the adult matrix. A little ujusn the chemical development after birth may be found in Moner (Schwalbe's Jahrcsber. f. 18811, 81-82J.

li, Fibro-cartilage appears first in the fonn of hyaline cartilage, and the fibrillw, which appear in the matrix and «eem to lie homologous with the ordinary intercellular connective-tissue fibrillw, are developed earlier or later.


7. Elastic cartilage also appears as hyaline cartilage, in which an elastic network is subsequently developed.


Degeneration of Oasirying Cartilage.— Besides the changes of a degenerative character, above refen-ed to, the skeletjil cartilages undergo a complete resorption, whenever in the course of development they are to be replaced by bone, except that in a few parts the cartilage is changtHl directly into bone. There lu-e two forms of the resorption of cartilage, the direct and the indirect. The direct \csorption occurs in only a few cases, as for instance in the gi-eater part of Meckel's cartilage, imd is cliaracterized by the gradual disapi)earance of the cartilage without any prece<ling striking change in it. The indirect resorption occurs whenever the development of bone begins in the interior of a cartilage, imd is accomi»anietl by very remarkable structural alterations in the cartilagt?. So far as 1 know no exact study of the direct resorption of cartilage has yet l>een made, while the indirect resorption has been investigtitcd again and again.


The indirect resorption begins in the centre of the cartilage; the first step in the process is an enlargement of the single cartilage cells, without much or any cliange in the amount of the matrix between them, but the matrix assumes a granular appearance and acquires a gritty feel to the knife owing to the formation of calcareous deposits. Meanwhile the cartilage alx)ve and below the ct-ntit^ of d<'gener.«tioTi becomes enlarged and piled up in elongatwl gniups or columns which radiate fn>m the centre for a certain distance towaitl tntlior end. The radiating columns of cells taper toward their ends away fi-oin the centre, the end cells lieing smaller. In the matrix l>etwecn the columns calcification takes place, so that calcified partitions seiuinite the columns from one another. Turning now to the cells we find that they are undergoing a hypertrophic degeneration, for their enlargement precedes their breaking down. There has been no sufiicient study of the changes in the cells, but so far as my own observations enable me to judge the changes are probably as follows. Fig. 238. The coll enlarges and its protoplasm becomes granular; the enlargement continues and the cell appears to encroach upon the matrix more and more until ultimately adjacent cell-cavities coalesce; while this corrosion of the matrix is progressing the protoplasm of the cell becomes vacuolated ; its nucleus becomes irregular and indistinct, and sooner or later disintegrates; the cell then contracts and forms a flattened body, which stains more or less, but exhibits no distinct structure, unless now and then some trace of the original nucleus ; after the cells have shrunk their cavities fuse together, and sooner or later the cells break down into mere granular det^:itus. The coalescence of the cell-cavities does not take place equally in all directions, but principally as shown in Fig. 238, along radiating lines ; hence there arise a series of radiating cavities separated by partitions formed by the calcified matrix. While these changes are going on in the interior of the cartilage, colmnns of the surrounding connective tissue go into the cartilage at various points, but always toward the degenerating tissue; each column contains blood-vessels also. As to why or how these columns penetrate the firm cartilage with their own soft tissues, we know nothing. The columns reach the centre of degeneration just as the cells of the cartilage break down and the ingrowing new connective tissue at once fills the spaces formed in the cartilage and proceeds in its new site to produce bone. The degenerative process now extends toward both ends of the cartilage and is followed b}' the formation of bone. The whole series of changes is commonly termed the ossification of cartilage, but this is incorrei*t, for the cartilage is destroyed, not ossified. The conjunction of the two sets of processes, Fig. 238, creates very singular microscopical pictures, which for a long time puzzled investigators. For further details see the following section on ossification.


Ossification. — Bone is a mesenchj-matous tissue, in which the cells have a characteristic shape and the matrix or intercellular substance is large in amount and calcified. It is derived always by a direct metamorphosis of embryonic connective tissue or of embryonic cartilage, and of periosteum. The ossification of cartilage plays a small part — for instance, at the angle of the jaw it has been ol)serv^ed to occur by J. Brock, 76.1, who found the cartilage cells changing into bone cells there, though nowhere else in the mandible. Most bones are formed bv the ossification of the connective-tissue cells or undifferentiated mesenchyma, and by layers of bone added by the ossification of the periosteum. Bony tissue after it is once formed does not grow except by additions to its surface. In the sim])lest form of ossification we have a laj^er or membrane of connective tissue, in which the tissue changes into bone ; this is called intramembranous, direct, or metaplastic ossification. The direct ossification of cartilage should also be placed under this head. As a modification of the simple ossification we must regard the ossification to replace cartilage, which is termed the intra-cartilaginous, indirect, or neoplastic ossiScation. In both types the actual processes of ossification are essentially the same, and the bone is completed by the co-operation of the periost. Metaplastic Ossification. — This may be conveniently studied in the jtariotal bone of the human embryo. About the end of the third month, in the parietal -A. , r^jion of the nicnibran ons skull there appear minute calcitied spicules, which mpi<lly increase in number and grow both in diameter and len^h so that they soon fuse t<)gether and farm an in-cfndar netwc^ik. Fig. ■^:ii;. The meshes of tlio network are lillwl with mesen(■hymal tflls, which are continually f or in in j^

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of the spicules. Somewhat later the fibrous iieriosteum appears ujton the surface of the young bone, and adds (wacons tissue to it.

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and more protoplasm so that, since the cells begin to enlarge as soon as they touch the bone, they are found to have grown considerably by the time they are completely imbedded. The connective-tissue cells, which lie against the bone, are known as osteoblasts^ a name proposed by Gegenbaur in 1864; though often close together they always are separated by distinct spaces from one another ; they are rounded, polyhedral, or triangular in form, and frequently are so crowded over the surface of the bone that they present a distinctly epithelioid an*angement ; the nucleus usually lies toward one side or end of the cell. The osteoblasts become imbedded in the bony matrix and thereby converted into bone c^lls, not by migration, but by the growth of the calcified matrix, the formation of which goes on first on the side of the osteoblast toward the bone, and gradually advancing overgrows the osteoblast and continues beyond it. The history of the intercellular threads of protoplasm during the transformation of the connective-tissue cell into an osteoblaist, and then into a bonecell, has, so far as I am aware, never been followed out. It seems to me probable that the threads are preserved and lead to the development of the canaliculi, just as the cell-bodies produce the so-called lacunae. Whether threads of protoplasm run through the canaliculi in the mature bone or not is still under dispute. Beside the osteoblasts in the interior of mandible there are others, Fig. 237, obl\ which are derived from the cells of the periost, per, and although the periosteal cells are of a very different character from those of the mesenchyma, vies, in the interior of the mandible, yet all the osteoblasts are alike. E. A. Schafer has directed attention to what he calls the osteoqenetic fibres* Upon close observation of the growing sj)icules of the parietal bone the calcified parts appear granular, and from them Schafer finds that there run out for a little way soft and j^liant bundles of transparent fibres. They exhibit a faint fibrillation and have been compared to bundles of white connective-tissue fibrils, witli which in some situations they appear to be continuous. But although similar in chemical composition, they are somewhat different from these in appearance, having a stiffer aspect and straighter course, besides being less distinctly fibrillated. The fibres become calcified by the deposition within them of earthy salts in the form of minute globules, which produce a darkish granular opacity, until the interstices between the globules also become calcified, and the minute *j;:lobules, becoming thus fused together, the bone again looks comparatively clear. It is stated that the fibrils themselves are not calcified, but the calcification affects the portion of matrix which unites them into the osteogenic fibres, so that these may be described as being calcified. The bundles of osteogenic fibres which prolong the bony spicules generally spread out from the end of each spicule so as to come in contact with those from adjacent spicules. When this hap|x^ns, the innermost or proximal fibres frequently grow totrether, while the other fibres partially intercross as they grow further into the membranb. The ossific process extends into the osteogenic fibres pari passu with their growth, and thus new bony spicules become continually formed by calcification of the groups or bundles of of lteogenir fibres. The earthy deposit not only involves the osteogenic fibres, but also the ground-substance of the tissue in which they lie. It cwcasionally appears in an isolated patch here and there on some of the osteogenic fibres in advance of the main area of ossification. The osteogenic fibres become comparatively indistinct as they and the substance between them calcifies; they appear, howover, to iKjrsist in the form of decussating fibres, such as are seen in the adult Ik me, although in the embryonic bone their disposition is less lamellatod, the bony matter having a somewhat coarsely reticular structure.

  • Tins account of the osteoj^euetic fibres is taken with some slight changes from Qtiaiu's "Aniit«»mv," nintli edition.


Neoplastic Ossification. — When bone replaces degenerated cartilage, the method of Inme formation is essentially the same as w^hen of ossification takes place in connective tissue, except for one feature, namely, that the bone is first deposited against the calcified remnants of the cartilaginous matrix as soon as the cartilage cells have disapi>eiired. A section through an ossifying long bone or vertebra. Fig. 2i3S, presents a highly characteristic picture, and if the sec'tion Ikj made as in the figure, p^irallel to the columns of cartilage cells, all the phases can be seen in a single successful preparation. The stH'tion figured was staineil with Beale's carmine and alum hajmatoxylin, by which method not only are the cells and nuclei brought out clearly, but also the calcified cartilage is made deep blue, while the lK)ne is deep i*ed. In the upper part of the figure, C, the Ciirtilag(^ cells are just forming groups or columns, wliich a little lower down, C, are very distinct ; lower down again, C\ the cavities, in which the columns of cartilage cells lie, have fused together into larg(» sj»m'(»s; in these spaces the cartilage cells, c, are scattered in various stages of disintegration; the adjacent spaces are separated from on<» another by partitions formed of ossified cartilaginous matrix, jl/a, whi(4i appears a deep blue in marked contrast to the unCidcifiinl matrix of the upper pjirt of the figure, where the matrix is almost uncolonnl. The remnants of calcified matrix extend far below the cartilagt\ At the level indicatcnl by the bnicket, L, the new mesi^nchyma, nies^ is found i)enetrating the spaces between the blue I^irtitions, M<t: the nu^simchyma is acctmipanied by blocxl- vessels, which an» eiusily nn'ogniztnl, V, by their endothelial walls. Some of tlu> invading mest»ncliymal cells lay themselves against the surfaces of th(» (*alcifie<l partitions, bt^come osteoblasts and prcxluce lx)ne, which thickens bv additions to its surfiu'e. Thus the calcified remains of the cartilage* Inn'ome coattnl with bone, which in the pn^paration descrilH^l has a rich nnl st^iin. As in the lower part of the figure the development is more advanced, we find there the layer of bone, B, much thickm- than neariT the cartilage. Fig. 23i) is a very acvurate drawing t)f }>jirt of ase<»tion of a vertebra of a four-months' embryo so made that the cn^lunms t)f cartilage ct»lls are cut at right angles; the level of the siH*tion CH>rn»siH^nds to the lower part ot bracki*t L, Fig. 2IIS. The cartilagt* ct»lls have disiipiK»aiiMl and have Invn rcplacinl by the invading niest»nchyma ; the network of jitirtitions formed by the n^nmants of the calcifitnl matrix, JAr, i»f tlu» cartilagi' is at once nHH)gniztHl, as can also Ixy n»i»i>gniziHi the transformation of the tH»lls into ost(H)blasts, <>/>/, and the deiK^sit of ])(>ne, B, upon the partition; noteworthy are idso the oste<.>clasts, Osc, to which fuller reference is made in the following paragraph on the growth o£ bone.

In the long bones the periosteal ossification has great importance, and as it pr<K'pe<ls vorj- rapidly at first in the central part of the bone, most of t}K' rthtift h fomied from the i^riost — compare Qnain's "Anat.," ninth ttlitiuu, II., Fig. 109.


We have learned that the development of hone may take place from embryoDic connective fibrillar tissue (periost), or from cartilage, hut whatever its origin, it has always nearly, if not quite, the same Btructure. This is true both of the cells and the matrix.


Historical Note.—l have purposely abstained from attempting a full history of ossification. For full and comprehensive accoimta I refer to Quain's "Anatomy," Ranvier's "Traite technique d'HistoIc^e," Kolliker's " Gewebelehre," Krause's " Anatomic," etc. For a good review of the literature up to 1858, seeH. Miiller, 68.2, and for

the


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references to the more importjint later authoritiea nee Rmvier's "Traite," RoUetf's chapter in Strieker's "Oewelielehre," und Masquelin's " Memoir."

Growth of Bone. — It is a well-known tm-t that tholionps do not grow in the onlinary sense; the bone cells cannot multi]ily; the apparent growth of Iwnc is acoomplialied by the destruction nf thelnme iJready forme<l and the pnxluction of new tM)ne. The dcHtrncti<in of the bone is effected by means of large multinucleate cell:*. Fig. 'i'M>, Ow, which are derive^l from the mesenchymal cell«, but jut<t how is not clear. The cells in (juestion have been named iiiiii-ii)i>l<i:ti'K (or myeloplacques), by Rohin luid French histologi.sts, and osU'iKlasis


(bone-deetroyere) by Kolliker. They are frequently found against the surface of the bone, on cartilage, Fig. 239, Osc\ and in that case lie in a little concavity formed by the eating away of the bone. As the development of these cells is not known and as their functions have been but little studied in the embryo, the detailed examination of their structure and history may be omitted here. Full accounts of the growth of bone may be found in all the standard histologies.


Disappearance of Intercellular Substance. — In the adult there are various spaces in the mesenchymal tissues, which are in the natural condition filled with fluid, such as the so-called lymph spaces and lymph channels ; these spaces have no cellular walls. In the lymph glands also there is much fluid between the cells and reticulum of the gland. We must, therefore, assume that the intercellular substance has in some way been rephiced, but whether it has been liquefied, or resorbed and fluid supplied in its stead, or simply cavities developed in it, we do not know. We can, therefore, do nothing more than note the gap in our knowledge.


Hypertrophy of Intercellular Substance . — By this I do not mean the increase which occurs in connection with the development of fibrillsB, elastic network, or cartilage, but the hypertrophy of the clear homogeneous matrix of the young mesenchyma or embryonic connective tissue. Such an hypertrophy occurs in the anmion, in the young cutis, and elsewhere, and it is probably the most important factor in the histogenesis of the vitreous and aqueous humors; as to how this hypertrophy is effected nothing is known. For the history of the vitreous humor see Chapter XXVIII.


Blood-Vessels are the earliest of the mesenchymal tissues to be differentiated. Their history has already been given in full. See Chapter X.


Lymphatic System consists of lymph spaces, lymphatic vessels, and lymph glands. The lymph spaces are merely channels in the intercellular substance, concerning the development of which nothing has been ascertained, and not much is known concerning the development of the vessels or glands.


Lymphatic Vessels. — Kolliker ("GeweMehre," 5te Aufl., 500GOO) states that in tails of tadpoles the lymph vessels can be seen developing, in similar maimer to the blood-vessels, by the hollowing »out of mesenchymal cells. Klein has come to the same conclusion from the study of the development of lymphatics in serous membranes. According to Klein a vacuole is formed within one of the cells of the connective tissue, and becomes gradually larger, so as ultimately to produce a cavity filled with fluid, while the protoplasm of the cell thins out to form the wall around the cavity. He also adds that from this wall portions bud inward into the cavity, and detaching themselves become lymph corpuscles — but this history cannot be ticcepted without better foundation. To form vessels the vesicular cells l)ecome connected together. The protoplasmatic walls become multinucleate and are differentiated into the lining endothelium. A. Budge's incompleted investigation of the development of the lymphatics in the chick, 87.1, wjis published posthumously by Professor W. His, and is an admirable piece of thorough work. The main part of the published memoir is devoted to the history of the formntion of the coelom by the fusion of a network of chaimels in the mesoderm, see p. 151. Budge states that after the coelom i8 developed some of the channels are still found in the somatopleure, and represent the primitive lymphatics ; the somatopleure at this sta^ has no bloDd-vessels and the splanclmopleure no lymph-vessels. The primitive lymph-veesels communicate directly with the coelom. ter on the ductus thoracicus appears and establishes the communication between the lymphatics and the blood-vessels. Unfortunately the published paper contains no details about the development of the ductus. In a short note (Cenh-albl. Med. Wiss., 1881, No. 34) Budge lias reported that in the allantois of a chick of eighteen to twenty days there are abundant lymphatics which can be injected with a subcutaneons sjTinge, The vessels accompanying the arteries, forming networks around them, Fig. 240, extend along the arteri» umbilicales to enter the body and run along the aorta (see Budge, 87.1, UO, and Ta£. VI., Fig. 2) as paired ducti, which are connected with one another by smaller cross stems, and unite in the upper ]>art of the tliorax into a single duct, which, however, again forks and has a double opening into the veins. The right umbilical lyinph stem appears to atrophy later. In connection with the allantoic

or b^iphatics Budge has found (see His and Lympbativi, Afu-r Aiijrecht Braune's At'ch. /, Aiiuf., 18S-*, ;t5(i) in chick embryos of ten tt> twenty days, lymph liearts, which Ho in the angle l»etwecn the jnilvis tmd coccj-x.


Lymph-Glands. — Concerning the developraent of the glands I know of three papers, Sertoli, 66.1, Chievitz, 81.1, and a dissertation by Orth (Boim, 1 STO) , which last I have not seen. KiUlikcr miotes alsoBreschet (" Li('8ystemel;y-mplii»tiiiue." Paris, 1>^;(I(, lH,=i) and Engel (Praij. \'i'frti!fj., II., ill, is.50)as maintaining that the glandu arise each iiH a i)lexu» of lymph vessels — a view which the observations of SL'rtoli have set aside. To study the early stages, glands must lie choMon, the exact position of whi<;h in i-elation to other [wrts can be determined, inordi^rthat tlio condition of the tissue l>L'fiire the dift'erentiatii^n of the gland can Ik* ast^ertained. With this in view Sertoli selected the niesentorial glands in cow emlirvus and Chievitz the same in the pig and tUe inguinid gland in man. Sertoli found in foiir-ineb eml)r>'o8 tissunw in the connective tissue of the mesentery whore the glands wore to apiHUU" in four-inch embryos these s]X)hj were further marked out by the crowding of nuclei around them. In six -and-a-half- inch embryos the anlagi-s were iieai-shajH-d, the pointed end Ix-ing h>ward the radix mesentcrii ; the jKiintt-d end alone (.■onttiins lymph Hi»aces, while the blunt end in which the nuclei are crowded is the anlage of the future cortex of the gland. Somewhat later the fibrous enveloijes of the ghuids aiis dift'LTeiitiated. and as soon as their formation begins, the growth of the glands by ;icces.sion from the surrounding mesenchjTna wasos. Chievitz studied the human inguinal gland ; its anlage is clearly recognizable at about three months, and at three and one-half months the cortical portion with crowded nuclei can be distinguished from the medullary, in which there are spaces ; the gland is separated from the surrounding tissue by a fissure which is crossed by a few threads; the fissure does not extend across the part of the gland corresponding to the future hilus ; the cells of the glands have large granular nuclei, and are easily distinguished from the lymphoid cells, which are much smaller with spherical refringent nuclei ; at first there are very few lymphoid cells, but they increase in niunber. Concerning the development of the reticulum, which Ranvier (" Traite technique," 678) has shown to be distinct in the mature glands from the branching cells, we have no information.


Spleen. — Although the development of the spleen must offer many points of great interest, it has received very little attention. In O. Hertwig's text-book no mention of the spleen is made; Kolliker, in both his text-books, dismisses the organ with a single brief paragraph. A little fuller is the notice by W. Miiller, in Strieker's " Handbuch der Gewebelehre," 260. Of special investigations there are three short ones, Peremeschko, 67.1, 2, and F. Maurer, 90.1, and the longer article on the spleen in fishes by E. Laguesse, 90.1.


The spleen is developed out of a mesenchymal anlage, which becomes recognizable in the human embryo toward the end of the second month. In all amniota it is situated in the mesogastrium near the pancreas, and close to large arterial vessels. Its first differentiation appears to be due to an acciunulation of rather large lymphoid cells with largo granular nuclei, and to the moving apart of the mesenchymal cells, which are much smaller than the lymphoid. Concerning the origin of the lymphoid cells we have only the observations of F. Maurer, 90, who found in tad|)oles, measuring from 0-8 mm. from mouth to anus, of the frog, Rana temporaria, that the entoderm gives off cells which pass into the mesenehj^ma and give rise to the first lymphoid cells. Maurer also obtained evidence that the same process occurs in the tailed amphibians. During the third month, in man (Kolliker), the blood-vessels penetrate the organ, which soon becomes rich in blood. W. Miiller states that the further development proceeds rapidl3% so that in the human foetus of eight centimetres in length the various constituents are already differentiated. The cells lying beneath the peritoneal epithelium become elongated, and form fusiform nucleated bodies, and similar ones at an early period invest the larger vessels. From both small processes are given off which grow toward one another and represent the commencement of the trabecular system. Along the arterial branches denser accumulations of small nucleated cells may already be discerned, which are conspicuous in tinted preparations by their deep color, and these form by far the chief constituent of the pulp. This consists of cells with from one to three nuclei and a delicate intercellular substance, forming plexuses, the interstices of which are constantly filled with blood-corpuscles. According to Peremescliko, there are now developed larger protoplasmic corpuscles in the tissue of the pulp containing from two to six nuclei, that are capable of performing amoeboid movements, and which, toward the end of embryonic life, atrophy. In the farther roar of derd^^tment the


Heveml ctmstituents increase in volume, aiid a pan of the fn&iform cells of the capsule and the vascular ^eaih? devek^p into ?nxiotb mutg'L'ular tissue. The arterial $heatb». cir^tainiog nmnerous txUs, are clearly distinguishaUe from the pulp, and fp_<m the middle of embrv'ooic life the Malpighian corpuscles are Tvo.^Dizalile. Concerning the Mze of the frjetal $p4een I kn>:>w i^clv <;.f the statement by Kolliker,<~rrundriss.~ 3>(>, that in man by the eighth week the anlage measures 0»2 1 O.31 mm., and in the third month 1.? x 1.13 mm.

In the embryo at six moDttui the spleen already has its triangular form in outline: the fibroai< sheath or capsule. C. is differentiated;


ela. (Tbe Embryu is


nr nil Monthi. C. raprnjl?: Itl. hllus:


tho hiluH, Hi, is wide; the main blood-vessels are remarkable for their Hizc, and aro encased in tlio sheaths of muscle fibres as in the arlnlt ; the differentiation of tho Malpighian coq>uscles is indicated by till! «'att<T(Nl urews, in which the cells are more crowde<l, which tln'ri'fonj itpiieiir darker in tho stained specimen. In a thin section (0,01 mm.) of )i somewhat younger spleen the reticulimi of the spleen, thii abiUKlatit IiIimkI ciipillaries, and the immense number of pulpwlls I find »ll well Khown ; tho pulp cells have round, finely granular iiufli'i with a vr-ry small amount of protoplasm ; I see also a much less nunilxT c(f smaller oval miclei, which seem to belong to tho reticulum. I^igiK^sse's immograph, 90. 1, on tho spleen of fishes is a conscientious and valuable work. Tho spleen apiK-ai-s lato, sometime after the iHincreas, in tho mesenchymal wall of tho duodenum close to and on tho left wide of tho insertion of the mesenterj-, and in close relation with thn Huliint<4itinul vein. The imlage is first recognizable by the ! condensation of tho tissue and the accumulatinn of free cells in its intmhos. Tho developing spleen gradually comes into closer rt'latioiiH with tlio stomach and seimrated from the duodenum, and is ultimately situated in the mesogastrium. The origin of the free cells was not ascertained, but the author is inclined to trace them to the mesenchyma rather than to accept F. Maurer's view. They are small, have rounded granular nuclei (Laguesse's noyau d^origine) and very little protoplasm ; according to Laguesse they give rise some to leucocytes, others to red cells; but in regard to this I think there is need of further evidence, for in other cases we know that leucoc^'tes and red blood-cells (h^maties) have different origins: The network is produced in situ by the mesenchymal cells, the processes of which gradually become more resistant, refringent, and homogeneous, while the nuclei gradually disappear more or less completely. This confirms the view so long defended by Kolliker, as to the nature of the reticuliun of the spleen. The cavities of the spleen form a rich network, which very soon enters into direct communication with branches which develop from the subintestinal (portal) vein, but the similar coimection with the arteries is not established until later ; after the arteries have penetrated there is a circulation through the spleen and many of its free cells are carried off, but in places aside from the currents there remain accumulations of multiplying free cells ; such accumulations are found especially around the large arteries. The veins in the spleen consist only of an endothelium, but in the adult are in part encased in a sort of basement membrane formed by condensation of the spleen reticulum around the larger vessels.


Smooth-Muscle Fibres. — That these ai-e simply modified mesenchymal cells seem to me no longer open to doubt, as explained in Chapter VI. on the mesoderm. This implies that the hypothesis so long uplield by His, that the muscles are genetically distinct from the connective- tissue elements, must be definitely laid aside. His classed the muscles as arcliiblastic elements His' pupil, Erik Miiller, has sought in a special article, 88.1, to justify His' view, but the history he gives is, that the inner mesothelium of the primitive segment breaks up into mesenchyma, and that some of these mesenchymal cells form the peri -endothelial walls of the aorta — a fact I can verify from my own observations on birds and mammals — but others of the cells, coming from the inner wall of the segment, form connective tissue, so that in this instance we have a proof of the identical, mesenchymal origin of the two tissues. So also in the umbilical cord, it can l>e seen after the third month that the vessels are surrounded by smooth muscle cells, which gradually pass into mesenchymal cells proper ; as the muscular walls thicken with age it seems evident that the transition represents an actual transfonnation of the connective-tissue cells into muscle cells, but the detiiils of the process have still to be worked out. The earliest definite proof, knowTi to me, that no line can be drawn between smooth muscle and connective tissue is that afforded by Flemming's observations, 78.2, on the bladder of salamanders, in which lx)th tissues with all intermediate forms occur.


Concerning the histogenetic transformation of mesenchyma into smooth muscle we possess no detailed or accurate information.


Fat-cells first appear in the human embryo, it is said, about the fourteenth week, and after their first appearance gradually increase in size and number up to the time of birth, when, however, the fat cells are still much smaller than in the adult. The fat cdls are derived from the embryunic connectire-tissup pelL<: or mesenchTma, as bafl been demonstrated by Flemmisg. 71. 1. 71.2. whose view was questioned by L. Ranvier (~ Traite~>, and the Hc^gans, 79. 1. Ranvier's obsei^-ations were incomplete, in that he did not ascertain the ori^n of the cell which forms the fat-oelb, as Flemming has pointed out in hiH reply, 79. 1 , to the criticism:- upon his work. The investi^tions of the Hoggans appear tr> me untrustworthy.

The fat cells are always developed in groups or clusters, and each cluster is supplied with an abundant network of blood capillarieB.



Tlin fat <i?ll.s alwayn (M-t;ur in tlio ni'iglilxirhood fif blood-vessels, so llmtdiii! is almost t-ciiii]M'1lt'd to cdiK-hido that sujK'ra bun daiit fotnl supply is an eswiitijil condition of tlicir ilcvolopment. Some interesting studies on the circulation in fjit tissue have been ]>ublished bv J. Schiibl, 85. 1. The clusters of fat ceils may l)c called fut islands, a tcnn li-ss likely to mislead students than tlmt of tat fjlobule, which has Wt'n used. Fi^. '-Jl- represents ii st'ction of a fat island in the embryonir^ cutis, drawn verj- exactly fnim the pn'ixinitioii, which had l><H>n stained with ahnn cooliineal and cosine; the nicsencln-mal «<lls, Men, aru scattcrtnl around and completely isolate the fat islands from one another; the fat cells, F^ form a group by themselves; each cell has a large globule of fat surrounded by a thin layer of protoplasm, which is thickened on one side, where the nucleus is situated; the smaller the cell the more distinctly does the layer of protoplasm stand out ; the nuclei are compressed, smaller than those of the surrounding mesenchyma, and more darkly stained ; the difference between the staining of the fat-cell and the other nuclei is exaggerated in the drawing. l3y their subsequent growth and expansion the fat islands may fuse together, thus forming a more or less continuous fatty layer.


As regards the history of the sing:le cells our knowledge rests chiefly on the admirable researches of Flemming, I.e. The cells lose their connections with one another and assume a somewhat rounded form, and the amount of protoplasm increases ; the nucleus comes to lie on one side of the cell either before the fat granules are developed or just iis they are beginning to appear ; according as the nucleus is peripheral or central the fat is at first on one side or around the I)eriphery of the ceil. In either case the fat soon collects in one main globule, with other small ones about it in the protoplasm, and thus the condition of the young fat cells, as in Fig. 242, is attained. Soon after the nucleus has been forced to one side by the fat the membrane of the cell appears. It is probable that the fat is accumulated within the cells before it becomes microscopically visible as granules, for Stolnikow {Arch. Anat. u. Physiol.^ SuppL, 1887, p. 1), has observed that the fat in the liver cells of frogs after phosphorus poisoning may be present in considerable quantities without appearing in granules. Upon this stress has been laid by Qaule, 90.1, as indicating that the fat is bound to some other compound, perhaps lecithin. This lends support to the suggestion of Poljakoff, 88.1, that tiie dull C' matten^') granules, which appear in the protoplasm before or along with the first minute fat granules and disappear as the fat increases, are made up of fat combined with some albuminoid.


The degeneration or regression of fat cells has been studied by Flemming and Poljakoff, but as the change does not occur before birth it does not fall within our scope, bej^ond noticing the suggestion that Ehrlich's Mastzellen (plasma cells) are regressive stages of fat cells.


Pigment Cells. — Concerning their development in the embryo I know of no exact investigation. WhatQoette gives, 75. 1, 521-522, is largely si)eoulative. Flemming, 90.1, has shown that the pigment cells multiply by indirect division in salamander larvae, and that the scission of the protoplasm may be delayed. K. W. Zimmermann, 90.1, has given some further details. The divisional process offers several interesting features.


The pigment granules which give color to the epidermis are not of epidermal origin, but arise in mesenchymal cells, which wander in from the underlying cutis. The source of the pigment was discovered bv Aebv, 85. 1, whose observations have been extended and confinned^by KGlliker, 87.2, 3, " Gewebelehre, " Ote Aufl., 202, List, 89.1, and Piersol, 90.2. Kodis, 89.1, on the other hand, has maintained that the pigment cells are formed in the epidermis and wander thence into the cutis, but Kodis fails, I think, to prove his point. In amniota the first pigment appears in small granular cells fill the basal layer of the epi«k-miis nizcinl. 4<"» mm.; chick of ten <lays; cat,4T mm.). The^se cells resem]>le leuci.>cytes so much that Kodis haij designated them as " If^ucocfftoifltf Zrllen_r they lie between the true epidermal cells; the pn»toplasni is small in amount when the pigment Ijegins to appear, but as the pigment increases the cell enlargt^s and [masses fn^m an appiirently round to a distinctly stellate fonn. In ///a/zi/z/a/.s the bodies of the cells are composed at tii'st of clear, homogeneous, faintly gnmular pn.»t«.»plasm. in the midst of which sliarply dotuied oval nuclei are seen : in short, they resemble the cells of the underlying cutis and are ]»rol>ably immigrant mejsenchymal cells. The earliest pigment particles are sparingly and irregularly distributed, but s<x)n evince a tendency to aggregate about the nucleus, ai-ound which a bn>wn wreath is soon formed. Subsequently pigment cells appear also in the cutis and exhibit a strong tendency to collect beneath the epidennis and to form there rich networks. These cells send processes into the epithelium, to be followed often by the greater part of the cell : it is thus that the pictures of inmiigrating pigment cells arise.


As to the source of the pigment granules, they seem to te formed within the pigment ct»lls and not to l>e taken up, as some writers have suggested, as preformed ])articles fnan outside. It is possible that the pigment is connected genetically with the htemoglobin, but of this there is no definite proof. For a discussion c»f the source of pigment granules see Maass (Arch. f. tnikrosl:. J //a/., XXXIV., 452) and Piersol, Lc.


Marrow. — The man*ow of Ix me is derived from the mesench^'ma, which, {is al>ove described, p. 4lU, enters the space left l>y the degenerating cartilage; some of these mesenchymal cells In^come osteoblasts, while the remainder produce the marrow of the future bone. The marrow has a very complex structure in the adult, and numerous investigations u|K)n its .adult structure have been published. In these publications are scattered a good many observations on the foetal marrow, but as th(»y liave never hiH^n proi)erly collated, and as there is no compr(.»hensivo resc»areh uiM)n the development of the foetal marrow, I ivluctantly forego the attt»nij)t to descrilx) the histogenesis of the tissue — a subject Avhich would certainly well repay competent thorough study. I will only add that the suggestion made by Ranvier (" Traite technique*), that the cells of the degenerating cartilage? pro<hK^(» marrow cells, cannot in my opinion 1)0 upheld, for it appears to me unquestionable that tli(j colls of the cartilage are disint(»grate<l.


Mesenchymal Cavities. — Under this lu^ad I do not include the blood-vessels, nor lymph-vesstels, uav the lymph channels of the interc<»llular substaiK'e and lymph spaces of the lymphatic glands, but only those* sjwices which have, so to s|K*ak, passive functions, are filled with serous tluiel, and arc* entin*lv Ijounded bv m(*st*nchvma. For example: the* channels around the membranous labyrinth of the ear (conj])are the s(»<'ond (livisi«)n on the ear in Chapter XXVII.), the subarachnoid spjice*, tluj synovial and bursal cavities. These are })rolMd)ly all form<»<l by th(» cells breaking apart, and are further charae'te'rizeMl by the te'ndency of the layer of mesenchymal cells imm«»<liat<'lv round the cavitv to IxHMnne* crowded until tlu*vform a distinct lining endothelium. The degree to which this tendency is evince<l varies extremelj', and we may have the cells either simply somewhat crowded, or converted into an endothelium in patches, or wholly endothelium. The transition from one form of tissue to the other can be seen in the adult synovial cavities, and is important as additional evidence of the slight real difference between mesenchyma and epithelium.


I know no observations on the development of the arachnoid spaces.


Synovial and Bursal Cavities. — The development of the synovial cavities htis been studied by Hagen-Tom, 82.1. Between the cartilages of the limbs there is left undifferentiated mesenchyma, which very early acquires blood-vessels and shows later an increased vascularity. The formation of the cavity begins in the centre between the cartilages, and is first indicated by the tissue becoming less dense there (rabbit embryos 19-20 nmi.) ; some of the central cells undergo a mucoid degeneration and disappear, others become spindle-shaped and change into Ciirtilage cells, with the result that the ends of the skeletal cartilages are now separated from one another only by a slight space. At the sides of the cavity the mesenchyma forms the s^Tiovigd membrane, which is merely XQTy vascular, fibrillar connective tissue; upon the synovial surface patches of endothelium are developed. Villi, if formed at all, appear in later stages and always at the sides of the cavity by the sjTiovial membrane proper.


Membranes. — The development of the various membranes and special mesenchj^mal layers, such as the submucosa, dermis, etc. , is considered in connection with the various organs, to which they belong. There is one general feature which may be mentioned here, namely, the so-called basement membranes. By this term is now generally understood the layers of endothelioid cells found immediately underneath various epithelia; for instance, under the entoderm (epithelium) of the intestine, around the Graafian follicles of the ovarv, around the seminiferous tubules, and the urinarv tubules. These membranes, often designated as tunicjo proprise, are undoubtedly the product of the mesenchyma, though nothing is known of their development. They have the general morphological interest of demonstrating the tendency of the mesenchyma to revert to the epithelioid type.


Ligaments and Tendons. — Both structures are modifications of fibrilliB and elastic connective tissue. The tendons consist almost wlioUy of fibrillsB running all in the same direction. The ligaments vary more, and may consist either of fibrillar or elastic tissue or both. The development of the ligaments has scarcely been studied; that of tendons has been investigated by L. Ranvier, 74.1, also his "Traite technique," 407; the regeneration and growth of the tendon tissue in the adult has been studied by several authorities — see A. Boltzow, 83.1. We learn, however, little beyond the fact that wliero tendon is to be formed the cells arrange themselves in rows, parallel with the length of the future tendon ; the fibrillae are developed between the rows and parallel to them, and gradually increase until they occupy the entire space between the ceUs. By what stages the cells pass from the condition of simple mesenchyma to the singular shapes of the adult tendon cells is unknown.



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Human Embryology: Introduction | The Uterus | General Outline of Human Development | The Genital Products | History of the Genoblasts and the Theory of Sex | The Germ-Layers | Segmentation | Primitive Streak | Mesoderm and the Coelom | Germ-Layers General Remarks | The Embryo | The Medullary Groove, Notochord and Neurenteric Canals | Coelom Divisions; Mesenchyma Origin | Blood, Blood-Vessels and Heart Origin | Urogenital System Origin | The Archenteron and the Gill Clefts | Germinal Area, the Embryo and its Appendages | The Foetal Appendages | Chorion | Amnion and Proamnion | The Yolk Sack, Allantois and Umbilical Cord | Placenta | The Foetus | Growth and External Development Embryo and Foetus | Mesenchymal Tissues | Skeleton and Limbs | Muscular System | Splanchnocoele and Diaphragm | Urogenital System | Transformations of the Heart and Blood-Vessels | The Epidermal System | Mouth Cavity and Face | The Nervous System | Sense Organs | Entodermal Canal | Figures | References | Embryology History



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