Ontogenesis of the Human Temporomandibular Joint 1. Development of the Condyles LOUIS J. BAUME Institut de Médecine Dentaire, Université de Genéve, Geneva, Switzerland Endochondral growth activity of the mandibular condyles, in contrast to epiphyseal plates of long bones, is responsive to induced stresses. This unique behavior of condylar cartilage is accompanied by peculiarities in phylogenesis, histogenesis, and metabolism which differ from the pattern of epiphyseal growth cartilages: (1) Phylo- genetically, the temporomandibular joint represents a new acquisition of the order of mammals; it replaces the articulation of higher reptiles between the articulare and the quadrate, which, in mammals, become ear ossicles (malleus, incus). (2) Histo- genetically, condylar cartilage accrues by surface apposition in a peripheral fibro- cartilage, whereas epiphyseal plates proliferate interstitially. (3) Metabolically, epi- physeal cartilages show much greater respiratory activity than found in articular car~ tilages.* The hormonal regulation of condylar development also differs from epiphyseal plates.4 The view has been expressed that this unique position of condylar cartilage among endochondral growth centers may be explained on the basis of its specific embryonic origin. A review of the literature recently presented by R. P. Cousin® reveals only scanty and contradictory information regarding the embryogenesis of condylar cartilage. Scott and Symons'—to our knowledge—are the only textbook authors to present authentic human material showing the first appearance of “secondary” condylar cartilage at the 48-mm, stage as a fringe on the dorsal end of the membranous dentale. This conforms with the observations made by Mundaca,$ while Kjellberg, 1904, Vinogradoff, 1910,2° Harpman and Wollard, 1938,!! Giardino, 1950, Gasparini and Marchetto, 1954, place this event at much later stages, from 85 to 120 mm., attributing to the lateral pterygoid muscle a decisive role. Politzer, therefore, states that the role of the sec- ondary cartilage in mandibular morphogenesis still warrants further investigation. Considering the great impact that a proper understanding of the physiology of the mandibular joint has on oral surgery in general and dentofacial orthopedics in partic- ular, we thought it worthwhile to pursue its morphogenesis in adequate human ma- terial. This includes 25 fetuses from 15 mm. crown-rump length to full term and 5 infants: two days, six months, nine months, and four years of age. Analysis of the serial sections has shown that 2 more or less independent blastemata—namely, the condylar blastema and the temporal blastema—are operating in the histodifferentiation of the joint structures. ‘This investigation was supported in part by a research grant from the Swiss Odontostomatological Society. 13271328 BAUME, J.D. Res. November-December 1962 ‘The prenatal and postnatal development of the entire temporomandibular joint will, therefore, be reported, partly in collaboration with K. Haupl in a series of 3 papers in the chronologic order of events: (1) the development of the condyles, (2) the develop- ment of the temporal components, (3) the postnatal growth and transformation. MATERIAL AND METHODS Data of material and methods used for this study of condylar histogenesis are seen in Table 1. Reference is made to a corallary study* that gives low-magnification micro- photographs of the sections here described. TABLE 1 DATA OF MATERIAL AND METHODS USED 7 | Crown Grom | Approx. Plane of Ne. Fetal Age Serial Length? F ae tanetht | Week Sec 1 15 | 6th7th | Sagittal 2 19 | "7th | Coronal 3 mw 8th | Goronal 4 25 8th | Sagittal 5 35 | Sth-9th =| Sagittal 6 35 | 8thoth | Coronal 7 4 9th Coronal 8 50 | omtoth | Coronal | Coronal e oo {Seatial 10. oo 11th Coronel Sagittal ud a & Coronal rat fn, sectioned serially 58 u; cach twentieth Section stained with H. ee th measured before fzation, Fiation reduces lengtnty Pik Hamilton, Bey and Mose, 195), {According toB. M. Patten (1948). RESULTS At the 19-mm., crown-rump stage, the bony dentary* originated from bilateral intra- membranous ossification centers in the integumental portions adjacent to the anterior end of Meckel’s cartilage (Fig. 1). ‘At the 24-mm. CR stage, these bilateral osseous centers have expanded posteriorly along Meckel’s cartilage toward the angle formed by the inferior dental nerve and the lingual nerve (Fig. 2). The orientation of this very thin bony plate was best appre- ciated by its relation to the primordia of the masticatory muscles, whose development precedes bone formation. Coronal serial sections showed that the median pterygoid muscle, partly connected with Meckel’s cartilage, ended distant from the lower border of the dentary; this, in a bend, tended to ossify in the direction of the muscle insertion (Fig. 34). At a more posterior level, below the auriculotemporal nerve (which branches off the bifurcating mandibular and lingual nerves), the origin of the lateral pterygoid muscle in its most primitive stage can be seen (Fig. 3B). The adjacent * The term “mandible” will be used after formation of the condylar cartilage head.1m. crown-rump human fetus, showing bilateral intramembranous fication centers of the dentaries (D) in the paramedian integument of the mandibular processes St = Stomodeum. (Orig. mag. X36.) Fic. 2 —Sagittal paramedian section of a 24-mm. crown-rump human fetus, evidencing the growth of the dentary (D) in dorsal direction by peripheral bone apposition. MC = Meckel’s cartilage; T = tongue. (Orig. mag. X36.) Fic. 3.—Coronal serial sections through the head of a 24-mm., CR human fetus showing, in an antero- posterior sequence, the various sites of the primordia of the masticatory muscles and the ossifying dentary. m = masseter, mpt = medial pterygoid muscle, = temporal muscles, dn = inferior dental nerve, J = lingual nerve, atu — auriculotemporal nerve, P = palatine process before fusion (posterior end), TR = tubo-tympanic recess, M/C = Meckel’s cartilage, D = dentary (mandible), and x = con- dylar blastema, (Orig. mag. X36.)1330 BAUM: J.D. Res. November-December 1962 mesodermal aggregation thus constituted the future area of the posterior portion of the ramus and condylar process; it may be termed “condylar blastema.” At the 35-mm. CR stage, fusion of the palatine processes was proceeding. This for- mation of a secondary palate was associated with a considerable downward displace- ment of the mandible-tongue complex (Fig, 4). There were, however, no morphologic indications that articulationing movements were involved, The chondrodesmosis be- tween Meckel’s cartilage (called “articulare” at its posterior broad end) and the quad- rate, though present, lacked the structural differentiation of a functioning joint (Fig. 5). The condylar blastema was found bilaterally in coronal sections which showed the Fras. 4-8—Coronal serial sections of a 35-mm. crown-rump human fetus are shown. Fig. 4: Over- all aspect of a coronal section, showing fusion of the palatal processes with nasal septum concomitant with downward development of the tongue-hyoid complex. (Orig. mag. X36.) Fig. 5: The primordial articulation of the mandibular arch formed by the end of Meckel’s cartilage (articulare) and quadrate in a region behind the outer ear anlage. A= articulate end of Meckel’s cartilage, Q = quadrate, 0 = otic capsule, RC = Reichert’s cartilage of the hyoid arch, and ST = ossifieation of the squamo- temporal plate. (Orig. mag. X36.) Fig. 6: Over-all aspect of a coronal section illustrating the topog- raphy of the condylar blastemata (x). Pch = prechordal plate of the cranial cartilage primordium, OS = orbito-phenoid p cartilage, OR = oropharynx, and T = ossification center of squamo” temporal bone. (Orig. mag. X13.) Fig. 7: Condylar blastema is shown at higher magnification. (Orig. mag. X55.) Fig. 8: Immature myoblasts (arrow) of the lateral pterygoid muscle forming the medial zone of the condylar blastema, D = distalmost ossification site of dentary. (Orig. mag. 210.)Vol. 41,No.6 ONTOGENESIS OF TEMPOROMANDIBULAR JOINT. 1. CONDYLES 1331 oropharynx below the prechordal plate and flanked by the orbitosphenoid cartilages which were perforated by the optic nerve (Fig. 6). The condylar primordium appeared as a rectangular area of condensed cells, laterally to and above Meckel’s cartilage and adjoined medially by the lateral pterygoid muscle, In this region, a new skeletal ele- ment in the form of the squamotemporal rod appeared; it extended from the post- auricular region toward the upper masseter origin (Figs. $~7). The dentary terminated as a semilunar bony spicule in the center of the dense agglomeration of mesodermal cells of the condylar blastema (Fig. 7). The lateral pterygoid muscle medial to the con- dylar blastema was still little developed, as it consisted of immature myoblasts (Fig. 8). At the 44-mm, CR stage, the dentary started to broaden, while posteriorly it further accrued in height and length, Expansive rapid osteogenesis was observed at 3 sites: at Fics, 9-11—Coronal sections of a 44-mm, crown-rump human fetus show the three sites of an increased growth of the dentary. Fig. 9: Rapid osteogenesis occurring at the lower border, where the masseter originated, and at the coronoid process. (Orig. mag, X36.) Fig. 10: A bulk of newly formed bone appearing at the base of the condylar process. The dentary accrued rapidly within the condylar blastema. ‘mn — mandibular nerve indicates site of future mandibular foramen. (Orig, mag. X36.) Fig. 11: At higher magnification of Fig. 10, the pattern of intramembranous ossification prevailing in the condylar blastema, A new mesodermal cell condensation (x) appeared at the lateral aspect of the condylar blastema, below the temporal joint primordium (7). (Orig. mag. X110.) the lower border, the upper coronoid end (Fig. 9), and the basal portion of the con- dylar process (Fig. 10). The posterior end, however, remained thin and bent inward. ‘The processes involved, as was seen at higher magnification, conformed with the pat- tern of intramembranous ossification (Fig. 11). Concomitantly, further differentiation of the condylar blastema took place; laterally in its outer layers, below the temporal bone, a new zone of mesodermal condensation was forming, At the 50-mm. CR stage, the entire periosteal circumference of the dentary showed deposition of new bone, but, at the 3 sites already previously noticed, it reached an extraordinary extent, In the basal and coronoid portions, this growth spurt resulted predominantly in a lengthening (Fig. 12), while, at the condylar end, widening was engendered (Fig. 13). The entire bulk of the newly formed tissue consisted of imma- ture fibrous bone (Fig. 14). The germinative layer at the condylar blastema was still very wide, containing copious mesodermal cells, particularly at the laterosuperior as-1332, BAUME J.D. Res. November-December 1962 pect, which foreshadows the future cartilage center. A wide, loose mesodermal tissue intervened the area below the squamotemporal bone. At the 55-mm. CR stage, as seen in the sagittal section of Figure 15, the condylar process is now topped by a condylar head, but with no cartilage present. The condyle lay at a higher level than the coronoid process. At its dorsosuperior aspect, the meso- dermal cell condensation of the condylar blastema was very wide. For the first time, processes of modeling resorption were found in the periosteum of the ramus. It was noted that no temporal elements of the future joint were present at this level ‘The coronal section (Fig. 16) also showed that the dorsal end of the condylar process had developed into a typically rounded condylar head, It consisted entirely of Figs. 12-14. jal sections through the developing dentary of a 50-mm, crown-rump human fetus are shown. Fig. 12: The coronoid process growing above the level of the suture of the temporal (T) and zygomatic (Z) bones. At its top and the lower border, sites of expansive osteo- genesis were seen, (Orig. mag. X36.) Fig. 13: Intramembranous ossification of the condylar process, showing an extraordinary extent. (Orig. mag. X55.) Fig. 14: At higher magnification, the center of rapid osteogenesis appearing at the laterosuperior aspect of the blastema (x). Note some osteo blastic activity of temporal bone rod. (Orig. mag. x 110.) young bone, which contained a large amount of round osteoblasts in a copious eosino- philic ground substance and a reduced amount of fibers (Fig. 17). This rapidly formed bone tissue thus started to lose identity. At the dorsolateral aspect of the head a carti- lage blastema became evident. At the 60-mm. CR stage, the decisive event of histodifferen m of secondary carti- lage at the condylar head could be observed (Fig. 18). But, simultaneously, cartilage also appeared at other sites of the mandible. In the anterior portion, lateral to the symphysis, Meckel’s cartilage was incorporated into the mandibular body by a process of endochondral ossification (Fig. 19). Cartilage also appeared at the 3 sites where previously rapid bone growth had occurred (Fig. 20). At the lower border of the ramus, osteogenesis passed a stage of secondary cartilage formation (Fig. 21). The fully differentiated chondrocytes were irregular in size and arrangement; the basophilic matrix was abundant and contained fibers but little hyaline. In its older portions, this secondary cartilage underwent coaVol. 41, No. 6 1333 calcification and, eventually, resorption by marrow elements (Fig. 22); direct ossifica- tion, producing a chondrosteoid tissue, also occurred. A huge ovoid mass of more regular cartilage was scen on the dorsal end of the coro- noid process (Fig. 23). Its base, however, consisted of newly formed trabecular bone, while in the more proximal sections calcified cartilage was present. All these phenomena were indicative of the great rapidity with which the ramus developed in an upward and backward direction, At the end of the condylar process, a fourth independent center of highly organ- ized cartilage had appeared (Fig. 18). It occupied, in the form of a spheroidal mass, the area that intervenes between Meckel’s cartilage and the squamotemporal rod, where the condylar blastema was previously found. Careful analysis indicated that the Fics, 15-17—The development of an osseous condylar head at the 5S-mm, crown-rump is shown, 15: A sagittal section showing the ofishooting development of an osseous condylar head (1), still topped by the condylar blastema (x). (Orig. mag. X30.) Fig. 16: The coronal section showing the formation of a primary osteal head of the condyle, which develops in a laterodorsal direction. Note relative aplasia of the temporal bastema. (Orig. mag. X30.) Fig. 17: At higher magnification, the persisting condylar blastema of a large mesenchymal cell condensation (x) at the laterodorsal aspect of the condylar head; this was the center of imminent chondrogenesis. (Orig. mag. X98.) cartilage-producing cells were located distant from the pterygoid insertion in the dorso- lateral mesenchymal covering of the head (Fig. 24). The upper medial portion of this covering produced a fibrous layer, which also assured the connection with the lateral pterygoid muscle (Fig. 25), while, in the basal periphery, periosteal osteogenesis was proceeding (Fig. 26). The condylar cartilage thus formed a cone whose top of the germinative cells faced the squamotemporal bone and whose basis containing the oldest chondrocytes faced Meckel’s cartilage. ‘The squamotemporal bone opposite the newly formed condyle showed some osteo- blastic activity (Fig. 18), but the differentiation of the temporal joint elements took place in a more posterior region, At the 72 mm. CR stage, serial sections made in both the coronal and the sagittal planes disclosed the following events as far as they concern mandibular development: At the basal portion of the ramus, secondary cartilage formation had completely ceased (Fig. 27), Previously formed cartilage had disappeared, partly through resorp-1334 BAUME J.D. Res. November-December 1962 tion, partly through ossification into a chondrosteoid tissue. Regular osteogenesis pro- ceeded within the periost. At the coronoid process, secondary cartilage formation also tapered off and was succeeded by rapid periosteal bone formation. Masses of a chon- drosteoid tissue were found more mesially in the core of this apophysis. At the condylar head, chondrogenesis, in return, showed accelerated activity. As seen from serial sections (Figs. 27-30), it had resulted in a considerable elongation of a cartilaginous condylar process. The oldest cartilage was found at the base of the coronoid process (Figs. 27, 28), from where it extended backward and upward into the Fics. 18-23.—Various sites of secondary cartilage appearing in the mandible at the 60-mm. crown rump stage. Fig. 18: A cartilaginous condylar head developing at the site of the previous condylar blastema. ‘The temporal bone shows increased osteogenctic activity. (Orig. mag. X36.) Fig. 19: Endochondral ossification within the anterior portion of Meckel’s cartilage in the GO-mm. fetus median symphysis, and 1/ = dental organ of lateral temporary incisor. (Orig. mag. X53.) Fig. 20: A coronal section at the level of the coronoid process, revealing three sites of secondary cartilage formation: at the top and the base of the coronoid process and at the lower mandibular border. (Orig, mag, X36.) Fig. 21; Higher magnitic 3. 20, showing irregular pattern of secondary cartilage formation. (Orig. mag. 210.) Fig. 22: The presence of chondroclasts in the bone marrow, indicating processes of cartilage resorption. (Orig. mag. X280.) Fig. 23: On top of the coronoid process more regular chondrogenesis proceeding; rapid osteogenesis ‘was seen at the basal portion. (Orig. mag. x 140.)Vol. 41, No.6 ONTOGENESIS OF TEMPOROMANDIBULAR JOINT. 1. CONDYLES 1335 condylar head, Periosteal bone formation invested the old carrot-shaped cartilage into the newly formed body of the ramus (Fig. 29). Rapid trabecular osteogenesis con- tributed to the formation of a mandibular angle (Fig. 29), Chondrogenesis proceeded from the dorsolateral portion of the mesodermal covering of the condylar head (Fig. 30). At its medial aspect, an enlarged tendinous attachment of the condylar head with the lateral pterygoid muscle had developed, At the base of the condyle, in preparation of endochondral ossification, capillary elements were seen to penetrate from the periost toward the degenerating chondrocytes (Fig. 31). Serial coronal sections of the pos- terior half of the condyle revealed a joint cavity that separated the condylar elements from the temporal joint structures. Differentiation of an articular disk and a glenoid fossa of the temporal bone was starting at a still more posterior level (Fig. 32) Fics. 24-26—60-mm. crown-rump stage continued. Fig. 24: At the condylar head, the center of rapid chondrogenesis found at the laterosuperior mesenchymal covering (1). The medial portion of this covering produced tendinous elements (2), while the basal portions were engaged in periosteal bone formation (3). (Orig. mag. X90.) Fig. 25: The medial center of tendon formation, (Orig. mag. X280.) Fig. 26: The laterosuperior center of chondrogenesis. (Orig. mag. X 260.) DISCUSSION Histodifferentiation of cartilage at the condylar head is a complex phenomenon related to the morphogenesis of the entire mandible and its connected organs. Among these organs, the masticatory muscles and possibly Meckel’s cartilage play a role. Muscle formation precedes intramembranous osteogenesis, Areas of future muscle attachment are sites of rapid bone formation throughout the early formative stages. There is a chronologic order in the appearance of these sites of growth spurt, pointing to a dorsal direction of development. ‘The first bone formed in the human body arises from a single intramembranous ossification center, in the paramedian integument, and develops by peripheral accretion into a primitive, thin plate. Giardino’s'? contention of 5-6 different mandibular ossification centers is not substantiated by evidence;* neither is the indication of Scott and Symons’ that this primary ossification center is situated near the bifurcation of the mental and incisal nerves. Expansive bone formation first *A similar conjecture is found in G. Dubreuil, Embryologie humaine, Paris: Vigot, 1941, and widely reproduced in the French literature.1336 BAUME J.D. Res, November-December 1962 occurs at the lower border in the vicinity of the ends of the masseter and internal pterygoid muscles. Another growth spurt in the region of the temporal muscle then produces the coronoid process, It is conceivable that primitive fibrillar muscular con- tractions may be conducive to these increased osteal growths. Since the lateral ptery- goid muscle remains undifferentiated, however, until the condylar head has developed, a different mechanism must be operative in the formation of the condylar process. Throughout the earliest stages, it was noticed that the dorsal end of the dentary remained particularly rich in undifferentiated mesodermal cells. We have designated Fics. 27-32.—Coronal serial sections through the posterior portion of the mandible of a 72-mm. crown-rump fetus are shown. Fig. 27: The ramus at the level of the coronoid process, showing com- plete cessation of chondrogenesis at the lower and the middle portions. (Orig. mag. %36.) Fig. 28: The oldest layers of calcified condylar cartilage appearing in the posterior base of the coronoid process. Note rapid trabecular bone formation at the lower border. (Orig. mag. X36.) Fig. 29: The anterior portion of the condylar head, showing calciiving cartilage invested in a periosteal bone splint. Note wide tendinous attachment of the lateral pterygoid musele. (Orig. mag. X36.) Fig. 30: The center of the condylar head, showing columnar arrangements of chondrocytes originating from a germinative layer at the laterosuperior surface (x), Note presence of articular space and trabecular osteogenesis at the mandibular angle (A). (Orig. mag, X36.) Fig. 31: At the lower periphery of the condylar head, some capillary loops penetrating from the periosteum toward the degenerating chondrocytes. ‘This is the very beginning of endochondral ossification, (Orig. mag. 280.) Fig. 32: Above the dorsalmost portion of the condylar head, a disk is forming. The temporal bone shows a site of second- ary cartilage formation (x). (Orig. mag. 36.)Vol. 41, No.6 | ONTOGENESIS OF TEMPOROMANDIBULAR JOINT. 1. CONDYLES 1337 this area “condylar blastema,” thus avoiding the hitherto used terms related to other elements of a future temporomandibular joint,*: 1 as they prove to have a different origin. Since bone tissue never grows interstitially and processes of modeling resorption do not occur at the early stages, it must be realized that any new bone formed in this condylar area will ultimately become a part of the more anterior portion of the dentary. Mandibular topogenesis engenders continuous changes in relationship, particularly to the attached muscles.1® Toward the end of the tenth week of fetal life, cartilage appears almost simul- taneously at various sites of the mandible. Three different patterns may be distin- guished: 1. At first, the anterior portion of Meckel’s cartilage undergoes endochondral ossifi- cation* and becomes incorporated into the mandibular body. Whether or not this invo- lution of the primordial cartilage has any bearing on the appearance of secondary cartilage warrants further study. 2. Then secondary cartilage formation occurs at the sites of the insertion of the medial pterygoid muscle, masseter and temporal muscle, where previously rapid trabec- ular osteogenesis was observed. The cartilage here formed is quite irregular and not highly differentiated. This passage of osteogenesis through a secondary cartilage stage may be explained on the basis of an extraordinary growth spurt. The very limited dura- tion of secondary cartilage production, in spite of a continued growth spurt, however, suggests that some internal conditioning factors or induction may be operative. 3. Histogenesis of condylar cartilage, from the very start, shows a highly organized pattern. It is the result of the final differentiation of the condylar blastema into the elements of a specific synovial articulation; chondroblasts originate from a germinative zone which is situated in the dorsolateral portion of the blastema; the capsular struc- tures and tendon of the lateral pterygoid muscle arise from the medial zone of this blastema, while its basal layers continue to form osteoblasts. Endochondral ossification does not occur until a relatively late period. The primor- dial condyles first increase in size both by chondrogenesis at the dorsolateral aspect and by osteogenesis along the neck, whereby the older calcifying cartilage is getting in- closed into the core. The developmental rates of the human head show an apparent reversal in the gen- eral embryogenetic law, which states that growth and differentiation progress gradual- ly in a caudal direction from rostrum to tail.28 Ford,2? however, has shown allometri- cally that after the tenth week of fetal life the anterior, prechordal, part of the cranial base elongates considerably faster than the posterior, chordal, part. The condylar blastema is located at a level anterior to the notochord. The onset of condylar cartilage formation coincides, in fact, with the growth spurt in the prechordal skeleton. The rela- tively late appearance of the mandibular growth cartilage thus is a phenomenon which is in perfect correlation with the delayed development of the prechordal segment of the mammalian skull. Although the mandible originates as a typical membrane bone, its final makeup in- volves other mechanisms which add to the unique position of the mandible among the * The onset of this mechanism of skeletal development implies a beginning thyroid-parathyroid activity which also presides over modeling bone resorption (Baume, Becks, and Evans, Am. J. Orthod., 39623, 1953)1338 BAUME J.D. Res, November-December 1962 bones of the skeleton: (1) endochondral ossification of the mediolateral portion of ‘Meckel’s primordium incorporates a cartilage-bone component, (2) differentiation of the condylar blastema into a secondary cartilage center adds a unique osteogenic phe- nomenon, and (3) growth and transformation of the mandibular symphysis, whose details are little known, constitutes still another peculiarity. Ontogenetically, the mandible, therefore, is truly a “mixed bone,” as originally con- ceived by Kélliker.2® SUMMARY Embryogenesis of the mandibular condyles was assessed in a material of 12 human fetuses of ascending stages from 15 to 72-mm. crown-rump length, It was found that condylar cartilage formation was a phenomenon closely related to the morphogenesis of the entire mandible and skull. Secondary cartilage appeared simultaneously at all sites of the insertion of the masticatory muscles. At the same time, the anterior portion of Meckel’s cartilage was incorporated into the mandibular body by a process of endo- chondral ossification. The condyle originated from a mesodermal condensation which was situated at the dorsal end of the dentary, in the vicinity of the proximal end of the lateral pterygoid muscle. This so-called condylar blastema appeared at the 24-mm. CR stage; at the early stages it contributed to the growth of the muscle and the dorsal prolongation of the dentary. At the 55-mm. CR stage, rapid osteogenesis led to the formation of a condylar head with no cartilage present. At the tenth week of fetal life (60 mm. CR), as the culmination of this growth spurt, chondrogenesis started at the dorsolateral portion of the blastema; concomitantly, the tendinous attachment of the lateral pterygoid muscle was differentiated, while, at the condylar neck, periosteal bone formation was proceeding. Endochondral ossification was not primarily involved in the formation of the condyles; it was still absent at the 72-mm. CR stage. Neither was there, up to this stage, any obvious developmental relations between condyle and tem- poral joint elements. ‘The late maturation of the condylar blastema was shown to coincide chronologically with the growth spurt of the prechordal segment of the cranial base. Ontogenetically, the mandible is a “mixed bone”’; it originated as a pure membrane bone, then incorporated elements of the Meckel’s cartilage primordium, and finally developed at various sites secondary cartilage. Of these, only the condylar cartilage persisted to form ultimately the highly organized growth center of the mandible. REFERENCES 1. Bauatx, L. J. Is the Condylar Growth Center Responsive to Orthodontic Therapy? An Experi- mental Study in Macaca mulatta, Oral Surg., Oral Med. & Oral Path., 14:347, 1961 : Response of Condylar Growth Cartilage to Induced Stresses, Science, 134253, 1961. 3. Wirrrenran, R. G., and Weroaann, S. M. Oxidative Enzyme Systems in Ossifying Cartilage, Biochem. J., 722667, 1959. 4, Bauer, L. J., Becks, H., and Evans, H. M. Growth and Transformation of the Mandibular Joint in the Rat Thyroidectomized at Birth, 7. The Effect of Growth Hormone and Thyroxin Given Separately or in Combination, Am. J. Orthodont., 39:623, 1953 5. Baume, L. J. Principles of Cephalofacial Development Revealed by Experimental Biology: The Second J. V. Mershon Memorial Lecture, Am. J. Orthodont., 47 :881, 1961. 6, Cousry, R. P. Embryologie et croissance de Particulation temporo-mandibulaire, Orthodont. Frang., 31:39, 1960.Vol. 41, No.6 | ONTOGENESIS OF TEMPOROMANDIBULAR JOINT. 1. CONDYLES 1339 7. Scort, J. H., and Sysons, N. B. B. Introduction to Dental Anatomy. Edinburgh and London: E. &S. Livingstone, Ltd. 1961. 8. Munpaca, C. L. Contribucién a la histogénesis de la articulacién témporomaxilar (“Articulus Mandibularis N.A.”) en la especie humana, Arch. espai. morfol, 6:175, 1948, 9. Kyettaere, K. Beitriige zur Entwicklungsgeschichte des Kiffergelenkes, Morphol. J., 32:159, 1904, 10. Vinocravorr, A. Développement de l’articulation temporo-maxillaire chez l'homme dans la période, intra-utérine, Intern. Monatsschr. anat. Physiol., 2° 0, 1910. 11. Harpman, J. A., and Woortarp, H. H. The Tendon of the Lateral Pterygoid Muscle, J. Anat. London, 73:12, 1938. 12, Grarorno, G. Ricerche anatomiche ed embriologiche sull'articolazione temporo-mandibolare, Atti Soc. napol. stomatol., 5:49, 1950. 13. Gasparnnt, F., and Marcuerro, G. Morfogenesi degli elementi scheletrici ¢ della architettura cap- sulo-sinoviale dell'articolazione della mandibola umana, Atti Soc. med. chir. Padova, 132:311, 1954, 14. Porrrzer, G. Die Entwicklung der Mundhéhle; in Hivet, Mever, and Scuucuaror, Die Zahn-, Mund- und Kieferkeilkunde, 1:297, 1958. 15. Baume, L. J. Die Entwicklungsmechanik des Mittelgesichtes in embryogenetischer Sicht, Deut. Zahn-, Mund- u. Kieferkeilk., 38:1, 1962. 16. Hasattrow, W. J., Boyo, J. D., and Mossacaw, H. W. Human Embryology (Prenatal Development of Form and Function). Cambridge: Heffer, 1959. 17. Patten, B. M. Human Embryology. Philadelphia and Toronto: Blakiston Co., 1948. 18, Lanvsaczer, J. M. F, Het kaakgewricht tijdens de embryonale ontwikkeling, Tijdschr. Tandheelk., 63:3, 1956. 19. Symons, N. B. B. The Development of the Human Mandibular Joint, J. Anat. London, 86:326, 1982 20. The Attachment of the Muscles of Mastication, Brit. D. J., 96:76, 1954. 21, Kinossury, B. F. The Significance of the So-called Law of Cephalocaudal Differential Growth, Anat. Rec., 27 :308, 1924. 22, Foxp, E. H. R. The Growth of the Foetal Skull, J. Anat. London, 90:63, 1956. 23. Kouraxer, A. Grundriss der Entwicklungsgeschichte des Menschen und der hiheren Tiere. Leipzig Wilhelm Engelmann, 1880.