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In an effort to better understand the interrelationship of the growth and development pattern of the mandible and condyle, a sequential growth pattern of human mandibles in 38 embryos and 111 fetuses were examined by serial histological sections and soft X-ray views. The basic growth pattern of the mandibular body and condyle appeared in week 7 of fertilization. Histologically, the embryonal mandible originated from primary intramembranous ossification in the fibrous mesenchymal tissue around the Meckel cartilage. From this initial ossification, the ramifying trabecular bones developed forward, backward and upward, to form the symphysis, mandibular body, and coronoid process, respectively. We named this initial ossification site of embryonal mandible as the mandibular primary growth center (MdPGC). During week 8 of fertilization, the trabecular bone of the mandibular body grew rapidly to form muscular attachments to the masseter, temporalis, and pterygoid muscles. The mandible was then rapidly separated from the Meckel cartilage and formed a condyle blastema at the posterior end of linear mandibular trabeculae. The condyle blastema, attached to the upper part of pterygoid muscle, grew backward and upward and concurrent endochondral ossification resulted in the formation of the condyle. From week 14 of fertilization, the growth of conical structure of condyle became apparent on histological and radiological examinations. The mandibular body showed a conspicuous radiating trabecular growth pattern centered at the MdPGC, located around the apical area of deciduous first molar. The condyle growth showed characteristic conical structure and abundant hematopoietic tissue in the marrow. The growth of the proximal end of condyle was also approximated to the MdPGC on radiograms. Taken together, we hypothesized that the MdPGC has an important morphogenetic affect for the development of the human mandible, providing a growth center for the trabecular bone of mandibular body and also indicating the initial growth of endochondral ossification of the condyle. Anat Rec 263:314–325, 2001. © 2001 Wiley-Liss, Inc.
The mandible, derived from the first branchial arch mesenchyme, remains one of the most debated topics in the morphogenesis of oro-facial structure. The mandible, comparable to long bone, is movable and antagonistic to the maxilla with the control of masticatory, facial expression, and some suprahyoid muscles (Azeredo et al., 1996; Bareggi et al., 1995; Lee et al., 1992). Anatomically, the mandible is connected to the temporal bone through the temporomandibular joint, innervated by a mandibular branch of the trigeminal nerve and serves important functions such as mastication, deglutition, and speech. Through the outcome of phylogenetic evolution it is likely that the mandible has evolved into more complex regulatory development via different pathways, i.e., muscular, alveolar, neural, and articular parts (Goret-Nicaise and Dhem, 1984; Jakobsen et al., 1991; Padwa et al., 1998).
Previous studies on mandibular development were focused mainly on the growth of condyle and symphysis (Bareggi et al., 1995; Ben-Ami et al., 1992; Berraquero et al., 1995; Bjork and Skieller, 1983; Kjaer, 1978b; Morimoto et al., 1987; Orliaguet et al., 1993b). A study on mandibular growth in an early human fetal development (weeks 8–14) revealed the mandibular ramus grew faster than the body, both in length and height; the greatest growth rate was found in the height of ramus; and the mandibular growth patterns differed significantly from those of successive developmental periods (Bareggi et al., 1995). Many authors had emphasized the importance of growth of the Meckel cartilage (Bhaskar et al., 1953), condylar head in mandibular growth (Kjaer 1978a; Morimoto et al., 1987; Shibata et al., 1996; Xu et al., 1983). A precise description of the prenatal human mandibular growth and developmental pattern, however, has not been reported.
The purpose of this study is to investigate a sequential growth pattern of the prenatal human mandible using radiological and histological methods. This study is intended to show how morphogenetic evidence of the prenatal mandible relates to the developmental mechanism and functional structure of the human mandible.
MATERIALS AND METHODS
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- MATERIALS AND METHODS
- LITERATURE CITED
Thirty-eight normally developed embryos and 111 fetuses were obtained from the Department of Pathology, Seoul National University Hospital after thorough gross and microscopic examinations. Gestational age of each embryo and fetus was deduced from the crown-rump length or maternal records. The 38 embryos aged from 5–8 weeks of fertilization (six at 5 weeks old; 19 at 6 weeks old; eight at 7 weeks old; and five at 8 weeks old, respectively). Embryos were fixed in 10% buffered formalin, embedded in paraffin, serially sectioned in 4 μm thickness on sagittal, transverse, or horizontal planes, and stained with hematoxylin and eosin. Twenty-three fetal heads developed early, ranging from week 9 to week 15 of fertilization (six at 9 weeks old; five at 10 weeks old; one at 12 weeks old; four at 13 weeks old; four at 14 weeks old; and three at 15 weeks old, respectively). Fetal heads were fixed in 10% buffered formalin, decalcified in 10% EDTA, pH 7.0, embedded in paraffin, and serially sectioned on frontal and horizontal planes in 4 μm thickness and stained with hematoxylin and eosin. The later-developed fetal mandibles (from 17 to 40 weeks of gestation) were removed and fixed in 10% buffered formalin. Removed mandibles were radiographed on lateral and vertical views using Faxitron (Hewlett Packard, Corvallis, OR) and soft X-ray film (Fuji, Tokyo, Japan). The specimens were decalcified in 5% nitric acid, embedded in paraffin, and longitudinal and cross sections of the mandibles were made in 4 μm thickness and stained with hematoxylin and eosin.
A point of concentric radiopacity at the apical area of deciduous first molar, from which linear trabecular bones radiate to all directions of the mandible, was named as the mandibular primary growth center (MdPGC). For the statistical analysis, five measurements of the fetal mandible were made on the lateral and vertical view: 1) the length of condyle growth was measured from MdPGC to condyle head (Co); 2) the length of anterior mandibular growth was measured from MdPGC to symphysis; 3) the length of posterior mandibular body growth was measured from MdPGC to mandibular angle (Go); 4) the length of anterior mandibular height growth was measured from upper border of alveolar (Al) bone to lower border (Lb) of mandible through the MdPGC; and 5) the length of posterior mandibular height growth was measured from Go to Co. The gonial angles formed by lower and posterior borderlines of the mandible at the mandibular angle were also measured (Fig. 1).
Figure 1. Measurements of prenatal mandibular growth. a, b: soft X-ray view of 24-week-old fetus, a; lateral view, b; vertical view, c, d: scheme of (a) and (b). Co, condyle head; Go, Gonion; Al, alveolar bone; Lb, lower border of mandible; MdPGC, mandibular primary growth center.
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Table 1. Incremental growth of mandibular measurements of human fetus on radiogram
|Fertilization age (week)||Cases(n = 111)||Co-MdPGC (mm)||Co-Go (mm)||MdPGC-Go (mm)||MdPGC-Sym (mm)||Al-Lb (mm)||Gonial angle|
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We observed that mandibular ossification started from the mandibular primary growth center (MdPGC), and that the mandibular growth pattern was characterized by intramembranous ossification of the mandibular body and endochondral ossification of the condyle. In our previous study, we explored the growth pattern of human prenatal maxillae and confirmed a pair of maxillary primary growth centers (MxPGC). The MxPGC showed the characteristic radiating, trabecular patterns by both the histological and radiological observations (Lee et al., 1992). It was suggested that the MxPGC is an initial ossification site of the maxilla. The MxPGC was an important anatomical landmark to analyze the stress-bearing maxillary structure, and remained as a sclerotic trabecular bone containing channels of nerve bundles and vessels later in fetal life, while major growth sites of the maxilla were at the distal ends of trabecular bones that radiated from the MxPGC. In this study we found a similar growth pattern in the mandibular development of human fetuses. During the developmental stages of the mandible, its primary growth center (MdPGC) was detected as a primary site of intramembranous ossification around the middle portion of the embryonal jaw. The MdPGC became the central part of the mandibular body, which appeared as a sclerotic focus of radiating trabeculae of the mandibular body shown on radiograms taken later in fetal life, whereas major growth sites of the mandible were at the distal ends of trabecular bones radiated from MdPGC.
The sequential development of the human mandible started from the middle of week 5 of fertilization, with the formation of core cartilage in mandibular swelling i.e., Meckel cartilage, and the mandible grew actively to form a mandibular arch protuberance. Three stages of Streeter's development appeared particularly important during the mandibular development: stage 16 (appearance of Meckel cartilage), stage 20 (beginning of membranous ossification), and stage 23 (end of the human embryonic period, week 8) (Orliaguet et al., 1993a). Many authors presumed that the Meckel cartilage, the first branchial arch cartilage, had no relationship to the processes of mandibular ossification (Merida-Velasco et al., 1993; Orliaguet et al., 1993b, 1994; Rodriguez-Vazquez et al., 1997a,b; Tomo et al., 1997). Unlike the long bones, Meckel cartilage entirely regressed during the later fetal period (Ellis and Carlson, 1986). In this study, however, we observed the primary intramembranous ossification of embryonal mandible developed in Streeter stage 19, earlier than the ossification of long bones usually found at Streeter stage 20 (Orliaguet et al., 1993a). We found that the intramembranous ossification as well as the condensed cellular mesenchyme of the condylar blastema was closely associated with a portion of perichondral fibrous tissue of the Meckel cartilage. Because the primary intramembranous ossification of the mandible greatly affects the following histomorphogenetic processes of the whole mandible (Bareggi et al., 1995; Berraquero et al., 1995; Orliaguet et al., 1993b, 1994; Rodriguez-Vazquez et al., 1997b; Tomo et al., 1997), we accentuate the primary intramembranous ossification and named it as the mandibular primary growth center (MdPGC). The MdPGC was approximated to the middle portion but lateral in position of the Meckel cartilage in the early embryonal period. Then, the trabecular bones originating from the MdPGC grew out rapidly toward the facial side, losing the relationship to the Meckel cartilage. These findings imply an important role of Meckel cartilage for the initial ossification of the mandible. We have also observed that the primary intramembranous ossification of the embryonic mandible did not encircle the Meckel cartilage the same as long bones but rather dislocated gradually to the facial side apart from the Meckel cartilage. It was also noted that the human Meckel cartilage did not undergo endochondral ossification unlike the core cartilages of long bones, although some animals showed calcification of the Meckel cartilage during the fetal period (Ishizeki et al., 1999; Tomo et al., 1997; Yamazaki et al., 1997). In the serial sections of human embryonic mandibles, however, we observed that the ossifying mandible and its attached muscles were detached from Meckel cartilage and dislocated outwardly as the lingual growth was advanced to fill the stomodeal cavity and to influence the mandibular movement. Thus, we hypothesize that early mandibular movement by the masseter and suprahyoid muscles may influence the premature dislocation of the primary mandible from Meckel cartilage in the early embryonic period.
From the serial sections of human embryos we also observed that the genioglossus muscle was attached to the perichondral fibrous tissue of Meckel cartilage in the early week 6 of fertilization. The genioglossus muscle was successively reattached to the inferior portion of mandibular symphysis at 12 week of fertilization. Other muscles, such as masticatory, mylohyoid, etc., were not attached but were positioned around the perichondral fibrous tissue of Meckel cartilage during weeks 6–7 of fertilization. When the intramembranous ossification of the mandible advanced to form multilayered linear trabeculae, the masticatory and mylohyoid muscles were attached tightly to the outgrowing mandible rather than Meckel cartilage during weeks 8–9 of fertilization. Although the direct histogenetic effect of Meckel cartilage on the embryonal induction of mandible remains unclear, we presume that the Meckel cartilage plays an important role to integrate the formation of human mandible, which was evolutionarily adapted to provide increased arch size and mobility. The question of “What influences the transition of the mandibular core skeleton from Meckel cartilage into mandible?” remained unanswered. It was suggested that it may depend on the early mouth opening movement, primarily induced by tongue musculature which matured quite early in orofacial structures (Bresin et al., 1999; Kang et al., 1992; Kiliaridis and Katsaros, 1998; Lee et al., 1990; Lightfoot and German 1998; Ogutcen-Toller and Juniper, 1993; Radlanski et al., 1999; Robertson and Bankier 1999; Sato et al., 1994). It was also reported that it may be influenced by mandibular movement in the human embryo beginning around week 8 of fertilization, when the temporomandibular joint is yet to be formed (Hall 1982a,b; Kjaer, 1997; Ouchi et al., 1998). Although the mechanism of an early mouth movement is unclear, it is apparent that the masticatory muscles do not induce the early embryonic mandibular movement at this stage because of their immaturity. We presume that the tongue movements directly induce the early mandibular movement, because Meckel cartilage, a primary skeleton of the mandible during weeks 5–7 of fertilization, was tightly attached to the genioglossus muscle. We also observed, however, that the primordia of the masseter, temporalis, and pterygoid muscles became attached to the newly formed mandible in the late week 8 of fertilization. This finding may imply that the early mouth opening movement causes the primordia of the masseter, temporalis, and pterygoid muscles relocate from the Meckel cartilage to the newly formed mandible moving along with tongue movement. Thus, we believe that the mandible supported by masticatory and tongue muscles would be able to control the development of the lower jaw as a new articulation without the influence of Meckel cartilage from approximately week 8 of fertilization.
The present study also indicates that the characteristic structure of the mandibular body exhibits a radiating trabecular pattern from the MdPGC that is closely related to the attachment of surrounding muscles. The pulling force of associated muscles may induce continuous appositional growth of intramembranous ossification on the periosteal side, rather than in the MdPGC, which is no longer proliferative later in fetal life. We suggest that the MdPGC is a primary ossification site of the fetal mandible, forming a rigid center of the mandibular structure. Serial sections of fetal mandibles showed that the linear trabeculae of the mandibular body were focused at the center of the MdPGC. In week 12 of fertilization, however, the architecture of the mandibular body was almost complete with the characteristic shapes of the mandibular body, coronoid process, mandibular angle, and symphysis. From week 15 to 16 of fertilization, the growth of mandibular body and condyle was clearly distinguished by radiography. The MdPGC clearly showed a radiating trabecular pattern originating from the apical area of the deciduous first molar tooth germ. This growth pattern of the mandibular body became most conspicuous during weeks 20–25 of gestation. The MdPGC was conspicuously detected near the apical area of the first deciduous molar tooth germ. Numerous linear bony trabeculae originating from the MdPGC grew peripherally, extending to the coronoid process, mandibular angle, symphyseal area, and even to the alveolar ridge (Fig. 8). Later in the fetal period, from week 30 of fertilization, the image of the radiating trabecular pattern was gradually overlapped with the image of tooth germs and peripheral cortical bone consolidated by muscular attachments.
A morphological study on the developing lateral pterygoid muscle and its relationships to the temporomandibular joint and Meckel cartilage indicated that all of temporomandibular joint structures and lateral pterygoid muscle assumed their adult shapes by week 14 of fetal life. At this stage, the lateral pterygoid muscle formed a complex structure with several aponeuroses dividing the muscle into three main parts: superior, inferomedial, and inferoanterior (Ogutcen-Toller and Juniper, 1993). This means that the muscular forces arising from mandibular movement directly influence the growth of the condyle and temporomandibular joint simultaneously. Thus, in this study we observed that the lateral pterygoid muscle was primarily attached to the condyle blastema tissue and became elongated through rapid condylar growth during weeks 8–10 of fertilization. This may imply that the lateral pterygoid muscle guides the conical condyle to form the temporomandibular joint. These data, however, suggest that the mandibular movement primarily controlled by the genioglossus muscle in the early embryonic period could affect the growth of the mandibular body and the condyle. Premature mandibular movement occurred at least 2 weeks earlier than the temporomandibular joint movement and stimulated the adaptational growth of the mandibular body and condyle. Thereafter, condyle growth was highly accelerated to form its conical structure and became independent of mandibular body growth.
The incremental growth of the mandibular dimension on the radiogram showed well-harmonized growth curves between the growth rate of mandibular body and condyle during the fetal period. The incremental growths of MdPGC-Sym, MdPGC-Go, and Al-Lb represent the pattern of mandibular body growth and the incremental growths of MdPGC-Co and Co-Go represent the pattern of condyle growth. The former group, however, showed a slightly reduced growth curve compared with that of the latter group. This may imply that condylar growth is much accelerated compared with those of the mandibular body. The slight reduction in gonial angle during the fetal period may also indicate increased growth of the condyle more in a vertical than a horizontal direction. These findings are concurrent with previous concepts of the mandibular development and growth (Baccetti et al., 1997; Bareggi et al., 1995; Buschang et al., 1999; Keith, 1982; Kjaer 1978a,b; Radlanski et al., 1999; Ronning, 1995).
In summary, we studied the sequential growth of the human fetal mandible and found that radiating trabeculae of the mandibular body focused into a primary growth center, MdPGC. From the MdPGC, the mandibular development was divided into two distinctive growth patterns of the mandibular body and condyle, as shown in Figure 8. We suggest that the MdPGC is an important anatomical landmark from which we can measure the growth directions or amounts of the mandible and that the MdPGC has an important morphogenetic implication for the development of human mandible, providing a growth center for the trabecular bone of the mandibular body and also indicating an initial growth of endochondral ossification of the condyle.