THE ANATOMICAL RECORD 263:314 –325 (2001)

Prenatal Development
of the Human Mandible
SUK KEUN LEE,1 YEON SOOK KIM,1 HEE SOO OH,2 KYU HO YANG,2
EUN CHEOL KIM,3 AND JE GEUN CHI4*
1
Department of Oral Pathology, Kangnung National University College of Dentistry,
Seoul, Korea
2
Department of Pedodontics, Chonnam National University Dental College,
Seoul, Korea
3
Department of Oral Pathology, Wonkwang University Dental College, Seoul, Korea
4
Department of Pathology, Seoul National University College of Medicine,
Chongno-gu, Seoul, Korea

ABSTRACT
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 attach-
ments 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 conspic-
uous 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 abun-
dant 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.

Key words: mandible growth; condyle growth; mandibular primary growth

center; human; fetus

The mandible, derived from the first branchial arch
mesenchyme, remains one of the most debated topics in
the morphogenesis of oro-facial structure. The mandi-
ble, comparable to long bone, is movable and antagonis-
tic 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). Ana-
tomically, 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, deglu-
tition, and speech. Through the outcome of phylogenetic
evolution it is likely that the mandible has evolved into
more complex regulatory development via different
Grant sponsor: Ministry of Health and Welfare, Republic of
Korea; Grant number: HMP-98-M-4-0048.
*Correspondence to: Je Geun Chi, MD, Department of Pathol-
ogy, Seoul National University College of Medicine, 28 Yongon-
dong, Chongno-gu, Seoul 110-799, Korea.
E-mail: pathr@plaza.snu.ac.kr
Received 22 August 2000; Accepted 15 February 2001
Published online 00 Month 2001

© 2001 WILEY-LISS, INC.

 DEVELOPMENTAL PATTERN OF HUMAN MANDIBLE
Fig. 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.
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 fo-
cused 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; Mori-
moto 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; Mori-
moto 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 in-
tended to show how morphogenetic evidence of the prena-
tal mandible relates to the developmental mechanism and
functional structure of the human mandible.
MATERIALS AND METHODS
Thirty-eight normally developed embryos and 111 fe-
tuses 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, respec-
tively). Embryos were fixed in 10% buffered formalin,
embedded in paraffin, serially sectioned in 4 ␮m thickness
on sagittal, transverse, or horizontal planes, and stained
315
with hematoxylin and eosin. Twenty-three fetal heads
developed early, ranging from week 9 to week 15 of fertil-
ization (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 ␮m 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 ␮m 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 sta-
tistical 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 mandib-
ular height growth was measured from Go to Co. The gonial
angles formed by lower and posterior borderlines of the man-
dible at the mandibular angle were also measured (Fig. 1).
RESULTS
Growth of Mandibular Body
In the middle of week 5 of fertilization (Streeter stage
16), a pair of Meckel cartilage appeared in the center of
mandibular arch along with the growth of mandibular
316 LEE ET AL.

TABLE 1. Incremental growth of mandibular measurements of human fetus on radiogram

Fertilization Cases Co-MdPGC Co-Go MdPGC-Go MdPGC-Sym Al-Lb Gonial
age (week) (n ⫽ 111) (mm) (mm) (mm) (mm) (mm) angle
14 1 14.1 4.5 8.0 — 4.0 150
15 2 15.10.5 6.50.0 9.50.7 5.90.4 4.30.4 1484
16 2 16.90.1 6.90.1 9.50.7 5.30.5 4.80.4 1484
17 1 17.2 7.0 10.0 6.4 5.0 —
18 4 18.32.0 7.50.6 10.50.4 7.0.1.1 5.00.7 1483
19 5 17.90.9 8.40.4 11.00.3 8.01.1 5.8 1423
20 7 20.90.6 9.90.5 12.41.3 8.21.0 7.40.6 1474
21 4 23.01.7 11.10.4 12.91.0 8.50.4 7.50.4 1448
22 3 23.32.3 11.00.5 12.80.3 9.10.0 7.30.6 1400
23 2 24.91.2 11.60.0 14.50.7 9.50.9 8.0 1450
24 3 25.74.5 11.80.7 15.20.8 9.31.6 9.01.0 1445
25 6 24.81.7 12.00.3 14.60.5 9.21.6 7.90.4 1465
26 3 26.01.8 11.90.2 16.20.8 10.40.3 8.80.3 1464
27 4 27.81.7 12.30.2 17.81.0 12.11.6 9.30.3 1467
28 4 27.02.6 13.10.6 16.60.8 12.72.0 9.90.6 1466
29 6 28.61.9 13.10.8 17.70.8 11.51.3 9.60.5 1416
30 10 29.62.6 14.30.6 18.21.0 13.22.4 10.70.8 1403
31 5 30.80.6 14.20.3 18.30.3 13.01.2 11.10.2 1414
32 5 31.22.0 14.80.8 17.40.5 11.92.1 10.70.4 1397
33 4 32.32.0 15.80.6 18.10.3 10.51.5 11.60.4 1447
34 3 32.91.4 17.00.5 18.71.2 15.52.2 11.30.6 1423
35 6 35.53.3 17.30.6 20.01.1 14.22.5 12.00.7 1438
36 4 35.12.9 17.00.8 20.31.3 13.30.9 12.50.6 1418
37 4 35.92.2 17.80.6 19.91.2 15.40.5 12.40.5 1404
38 10 35.12.9 18.21.2 21.21.4 13.90.9 13.40.8 1367
39 3 39.32.6 19.80.3 22.30.6 15.51.6 12.80.8 1395

nerves and vessels to form the hyaline cartilaginous
tissue and thick perichondral fibrous mesenchyme.
From the middle of week 6 of fertilization (Streeter
stage 19), the mandibular ossification appeared as in-
tramembranous bony apposition in close approximation
to the Meckel cartilage. The initial intramembranous
ossification of the mandible began at the facial fibrous
mesenchyme around the Meckel cartilage, with a direct
contact (Fig. 5a), or an encirclement with the Meckel
cartilage in contrast to the other long bones. In week 7
of fertilization (Streeter stage 21), the linear trabeculae
of mandible developed anteroposteriorly from the initial
ossification of the mandible. Serial sections revealed
that these linear trabeculae branched toward the future
mandibular symphysis, alveolar bone, mandibular
body, and coronoid process. At this time, the genioglos-
sus muscle (Fig. 5b,c) was tightly attached to the lower
side of the anterior portion of Meckel cartilage, whereas
the primordium of masticatory muscle was located
around the middle portion of Meckel cartilage, i.e., mas-
seter as well as temporalis muscles on the facial side
and pterygoid muscle on the lingual side of Meckel
cartilage respectively. As the ossification of mandible
progressed into the week 7– 8 of fertilization (Streeter
stage 22–23), the muscular attachment of the genioglos-
sus muscle gradually changed from Meckel cartilage
into the anterior portion of linear trabeculae of mandib-
ular symphysis (Fig. 5b). The primordia of masticatory
muscles (Fig. 6a), i.e., masseter, temporalis, and ptery-
goid muscles, departed from the Meckel cartilage and
repositioned around the linear trabeculae of mandible.
Late in week 9 of fertilization, the serial sections of
masseter and temporalis muscles showed muscular at-
tachment to the buccal side of mandibular body and
coronoid process, respectively. The pterygoid muscle
(Fig. 6c), which had been primarily located on the lin-
gual side of Meckel cartilage, was far from the lingual
side of mandibular body, because the mandibular body
was gradually shifted toward the facial direction. Si-
multaneously, the pterygoid muscle gradually moved
toward the posterior portion of mandibular body and
was divided mesially and laterally respectively; the
former attached to the lingual side of posterior mandib-
ular body and the latter attached to the posterior end of
linear trabeculae of mandible, but not to Meckel carti-
lage. Serial sections of the embryonic jaw also revealed
that the thinned fibrous mesenchyme around Meckel
cartilage was traced to the thickened periosteal mesen-
chyme of mandible. Subsequently, the condyle blastema
appeared with the condensation of cellular mesenchyme
at the posterior end of linear trabeculae of the mandible
with an attachment to the lateral pterygoid muscle. In
week 10 of fertilization, the mandibular ossification ad-
vanced to form an anatomical structure of the lower jaw
including the mandibular angle (Fig. 7a), coronoid pro-
cess (Fig. 7a), and symphysis (Fig. 5e). By this time, the
lower part of genioglossus muscle was attached to the
lower portion of mandibular symphysis, while the upper
part of genioglossus muscle was still attached to the
anterior portion of Meckel cartilage. In week 11 of fer-
tilization, as the anteroposterior growth of the mandible
increased with multilayered bony trabeculae, then the
upper part of genioglossus muscle was almost detached
from Meckel cartilage. The site of initial intramembra-
nous ossification of the mandible (Fig. 5d), however,
remained approximate to the Meckel cartilage (Fig.
5d,f,g). In week 12 of fertilization, most of the genioglos-
sus muscle was attached to the lower portion of anterior
 DEVELOPMENTAL PATTERN OF HUMAN MANDIBLE 317

Fig. 2. Growth pattern of prenatal mandible by soft X-ray view, lateral view of mandible. a: 16-week-old
fetus; b: 17-week-old fetus; c: 18-week-old fetus; d: 20-week-old fetus; e: 25-week-old fetus; f: 30-week-old
fetus; g: 34-week-old fetus; h: 38-week-old fetus.
318 LEE ET AL.

Fig. 3. Incremental growth of representa-

tive measurements of prenatal human mandi-
ble. Co-MdPGC, length from condyle head to
mandibular primary growth center; MdPGC-
Go, length from mandibular primary growth
center to Gonion; Co-Go, length from condyle
head to Gonion; MdPGC-Sym, length from
mandibular primary growth center to mandib-
ular symphysis; Al-Lb, length from alveolar
bone to lower mandibular border.

Fig. 4. Changes of gonial angle during fetal period.

Fig. 5. Relationship between Meckel cartilage and mandible during morphogenetic stage of human embryos. a: Six weeks old, mandible (Md)
appears at facial side of Meckel cartilage (Mc) (HE, ⫻40). Tg, tongue; DL, dental lamina. b: Eight weeks old, lingual side of Meckel cartilage is not
covered with intramembranous ossification of mandible, note the genioglossus muscle (Gg) attached tightly both on the lower side of anterior portion
of Meckel cartilage and on the portion of mandibular symphysis (HE, ⫻20). Mx, maxilla; UL, upper lip; LL, lower lip. c: High magnification of (b),
intramembranous ossification of mandible is closely associated with the fibrous mesenchyme of Meckel cartilage (HE, ⫻70). d: Eleven weeks old,
mandibular ossification continuously grows outwardly from Meckel cartilage with a direct contact (HE, ⫻70), square; site of initial intramembranous
ossification. e: Ten weeks old, frontal section, newly formed mandibular arch is larger than Meckel cartilage arch (HE, ⫻60). Sym, symphysis. f:
Eleven weeks old, horizontal section of mandible shows the initial ossification site of mandible that was named as mandibular primary growth center
(MdPGC) (HE, ⫻10). SM, submandibular gland; Hy, hyoid cartilage. g: High magnification of (f), the MdPGC showed ramifying trabecular structure,
the portion of Meckel cartilage approximated by MdPGC was rapidly resolved (arrows) (HE, ⫻60). h: Twelve weeks old, sagittal section showing
longitudinal alignment of Meckel cartilage and linear trabecular bone of mandible (⫻5). TG, trigeminal ganglion; SM, submandibular gland; IE, inner
ear organ; Ey, Eye. i: High magnification of (h), the linear trabeculae of mandible was approximated to the anterior portion of Meckel cartilage (⫻70).
To, tooth germ. j: Ten weeks old, hyalin cartilage with intact cellular morphology (inlet, ⫻1,000) (HE, ⫻200). k: Twelve weeks old, the chondrocytes
were swollen and some of them disappeared (arrows) (HE, ⫻400). l: Twenty weeks old, the Meckel cartilage was shrunken and separated from
mandible (HE, ⫻200). m: high magnification of (l), peripheral chondrocytes were gradually resolved (arrows) (HE, ⫻1,000).
DEVELOPMENTAL PATTERN OF HUMAN MANDIBLE 319

Figure 5.
320 LEE ET AL.
mandible to form the median symphyseal structure. As
a result, Meckel cartilage became completely detached
from the linguo-mandibular architecture (Fig. 5f,g) and
rapidly decreased in size (Fig. 5h,i). At this stage, the
Meckel cartilage became atrophic and its perichondral
fibrous mesenchyme remained thin, and its hyaline car-
tilage tissue also showed degenerative changes of chon-
drocytes, i.e., enlarged empty lacunae without nuclei or
pyknotic/karyorrhectic nuclei (Fig. 5j,k). The cartilage
matrix and chondrocytes of the Meckel cartilage were
gradually shrunken and finally resolved with infiltra-
tion of tissue macrophages into the perichondral fibrous
tissue. The Meckel cartilage, however, showed no endo-
chondral ossification until later in fetal life (Fig. 5l,m).
From week 12 of fertilization, the intramembranous
bony ossification was active at the periphery of ramifying
trabeculae of the mandibular body, coronoid process and
symphysis. The central trabecular bone became thick and
sclerotic (Fig. 5h,i). During weeks 13–15 of fertilization,
the mandible grew as multilayered trabeculae radiating
from the primary ossification site of the embryonic man-
dible, namely the mandibular primary growth center (Md-
PGC). From week 16 of fertilization, the radiating trabec-
ulae of mandible could easily be demonstrated by a soft
X-ray view. Thereafter, the radiating trabecular bones
from the MdPGC corroborate the mandibular body growth
during later in fetal life (Fig. 2). The radiological dimen-
sions of MdPGC-Sym and MdPGC-Go, which represent
the growth of anterior and posterior body of mandible
respectively, showed similar incremental growth rates
during the fetal period. The incremental growth rate of
Go-Co, representing the posterior mandibular height, was
higher than that of Al-Lb, representing the anterior man-
dibular height. The incremental growth rate of Al-Lb was
similar to those of MdPGC-Sym and MdPGC-Go during
the fetal period (Fig. 3). The gonial angle was measured
about 146 –148° in an early fetal period, and decreased to
141–143° until late in fetal period (Fig. 4).
Growth of Condyle
In the early week 7 of fertilization (Streeter stage 21), a
group of cellular mesenchymal tissue was formed around
the posterior end of linear trabeculae of the mandible (Fig.
6a,b). In serial sections, this cellular mesenchymal tissue
was traced to the fibrous mesenchyme around the Meckel
cartilage (Fig. 6c). A branch of pterygoid muscle was
clearly associated with the condensed mesenchyme late in
week 7 of fertilization. Early in week 8 of fertilization
(Streeter stage 23), the posterior end of linear trabeculae
of the mandible showed an increased osteoblastic hyper-
plasia and was well surrounded by the condensed mesen-
chyme that produced a condyle blastema, to which the
lateral pterygoid muscle was attached. From early in week
9 of fertilization, however, the blastema of the condyle
produced a cartilaginous tissue forming a condylar head
at the posterior end of linear trabeculae of the mandible.
The condyle grew rapidly with the bony deposition of
endochondral ossification. As the condyle was elongated
upward and laterally, a part of pterygoid muscle moved
along with the condyle head. Simultaneously, the ptery-
goid muscle was divided into mesial (internal) and lateral
(external) groups (Fig. 6d,e). The mesial pterygoid muscle
remained at the mesial side (lingual or internal side) of
the mandibular body, while the lateral pterygoid muscle
moved continuously upward and laterally (externally) in
concert with the rapid condyle head growth. Expansive
growth of the cartilaginous condyle head produced a con-
ical bony structure, which was in contrast to the adjacent
mandibular body growth on radiograms and histological
sections. In week 12 of fertilization, the conical shaped
condyle was elongated toward the temporal squama to
form the temporomandibular joint. Thereafter, the con-
dyle grew in a characteristic conical shape. The condyle,
composed of a distally thickened cartilaginous cap and
proximally thinned apex, converged toward the MdPGC
(Fig. 7a–f), where bundles of vessels and nerves were
located (Fig. 7g). The conical condyle contained abundant
hematopoietic cells in its marrow space, and formed a
curve along the angulation from the ramus to the man-
dibular body as it’s growth advanced (Fig. 7h,i). The
amount of incremental growth of the conical condyle (Co-
MdPGC), however, was highest in the representative an-
atomical dimensions of the human mandible during the
fetal period (Fig. 3).
DISCUSSION
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 char-
acteristic radiating, trabecular patterns by both the his-
tological 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 ana-
tomical 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
Fig. 6. a– d: Condyle growth. e– g: Cross section of mandibular body. a:
Seven weeks old, condyle blastema (CB) developed from the posterior
end of linear trabeculae of mandible (HE, ⫻40). Tp, temporalis muscle;
MN, mandibular nerve; LPt, lateral pterygoid muscle; MPt, mesial ptery-
goid muscle; Ms, masseter muscle. b: High magnification of (a), the
condyle blastema consists of active osteoblastic deposition (arrow) and
abundant mesenchymal condensation (HE, ⫻400). c: Eleven weeks old.
d: Twelve weeks old. e: High magnification of (d), condyle blastema (CB)
attached by lateral pterygoid muscle (LPt) grew toward temporal bone
(Te), note upper lateral pterygoid muscle (ULPt) and lower lateral ptery-
goid muscle (LLPt) (HE, ⫻40). f: Sixteen weeks old, cross section of
mandible at first deciduous molar area (To), retrogressive Meckel carti-
lage (Mc) is remained at the lingual side of mandible (Md) (HE, ⫻40). g:
High magnification of (f), the Meckel cartilage (Mc) has no direct con-
nection to mandibular ossification (HE, ⫻200). h: Twenty weeks old,
cross section of mandible, the Meckel cartilage (Mc) is rudimentary and
almost isolated from the mandible (Md) (HE, ⫻40).
DEVELOPMENTAL PATTERN OF HUMAN MANDIBLE 321

Figure 6.
322 LEE ET AL.
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 (appear-
ance of Meckel cartilage), stage 20 (beginning of membra-
nous ossification), and stage 23 (end of the human embry-
onic period, week 8) (Orliaguet et al., 1993a). Many
authors presumed that the Meckel cartilage, the first
branchial arch cartilage, had no relationship to the pro-
cesses 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, ear-
lier 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 con-
densed cellular mesenchyme of the condylar blastema was
closely associated with a portion of perichondral fibrous
tissue of the Meckel cartilage. Because the primary in-
tramembranous ossification of the mandible greatly af-
fects 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 man-
dibular 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 ossi-
fication 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 endo-
chondral 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 dislo-
cated 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 man-
dible 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 suc-
cessively 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 ad-
vanced to form multilayered linear trabeculae, the masti-
catory and mylohyoid muscles were attached tightly to the
outgrowing mandible rather than Meckel cartilage during
weeks 8 –9 of fertilization. Although the direct histoge-
netic 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 forma-
tion of human mandible, which was evolutionarily
adapted to provide increased arch size and mobility. The
question of “What influences the transition of the mandib-
ular core skeleton from Meckel cartilage into mandible?”
remained unanswered. It was suggested that it may de-
pend 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 em-
bryo 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 be-
cause of their immaturity. We presume that the tongue
movements directly induce the early mandibular move-
ment, 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 move-
ment 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 con-
trol the development of the lower jaw as a new articulation
without the influence of Meckel cartilage from approxi-
mately 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 appo-
sitional 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 trabec-
ulae 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
 Fig. 7. Growth pattern of mandibular body and conical condyle. a:
Twenty weeks old, longitudinal section of mandible, conical condyle
growth (C) is characteristic (HE, ⫻5). CP, coronoid process; MA, man-
dibular angle; Sy, symphysis; ToD, deciduous first molar tooth germ;
ToE, deciduous second molar tooth germ. b: Twenty-five weeks old,
tube like condyle growth is conspicuously demarcated (arrows) (HE, ⫻7).
EA, external auditory meatus. c: Twenty-seven weeks old, rapid growth
of conical condyle (arrows) (HE, ⫻10). d: Twenty-eight weeks old, con-
ical condyle growth is clearly distinguished by its trabecular pattern
(arrows) (HE, ⫻10). e: Thirty-five weeks old, conical condyle remained as
sclerotic bone (*) (HE, ⫻10), ToC, deciduous canine tooth germ; To6,
permanent first molar tooth germ. f: High magnification of asterisk (*)
area of (e), still the trabecular structure of conical condyle growth (ar-
rows) is different from that of mandibular body growth (HE, ⫻40). g: High
magnification of arrow area of (e), dilated vessel (V) and thick sclerotic
trabecular bone around the MdPGC (HE, ⫻200). h: Thirty weeks old,
cross section of mandible at deciduous second molar (ToE) area, the
conical condyle growth is demarcated by arrows, and it contains hema-
topoietic tissue in the center (HE, ⫻10). i: Thirty weeks old, longitudinal
section of mandible, hematopoietic tissue (*) is abundant in the marrow
space in the conical condyle growth (arrows) (HE, ⫻100).
body and condyle was clearly distinguished by radiogra-
phy. 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 man-
dibular body became most conspicuous during weeks
20 –25 of gestation. The MdPGC was conspicuously de-
tected near the apical area of the first deciduous molar
tooth germ. Numerous linear bony trabeculae originating
from the MdPGC grew peripherally, extending to the coro-
noid 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 im-
age of tooth germs and peripheral cortical bone consoli-
dated by muscular attachments.
A morphological study on the developing lateral ptery-
goid muscle and its relationships to the temporomandib-
ular joint and Meckel cartilage indicated that all of tem-
poromandibular 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 com-
plex structure with several aponeuroses dividing the mus-
cle into three main parts: superior, inferomedial, and in-
feroanterior (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 Fig. 8. Representative scheme for mandibular body growth (upper)
primarily attached to the condyle blastema tissue and and condyle growth (lower).
became elongated through rapid condylar growth during
weeks 8 –10 of fertilization. This may imply that the lat-
eral pterygoid muscle guides the conical condyle to form
the temporomandibular joint. These data, however, sug- of the mandibular body and condyle, as shown in Figure 8.
gest that the mandibular movement primarily controlled We suggest that the MdPGC is an important anatomical
by the genioglossus muscle in the early embryonic period landmark from which we can measure the growth direc-
could affect the growth of the mandibular body and the tions or amounts of the mandible and that the MdPGC has
condyle. Premature mandibular movement occurred at an important morphogenetic implication for the develop-
least 2 weeks earlier than the temporomandibular joint ment of human mandible, providing a growth center for
movement and stimulated the adaptational growth of the the trabecular bone of the mandibular body and also in-
mandibular body and condyle. Thereafter, condyle growth dicating an initial growth of endochondral ossification of
was highly accelerated to form its conical structure and the condyle.
became independent of mandibular body growth.
The incremental growth of the mandibular dimension ACKNOWLEDGMENTS
on the radiogram showed well-harmonized growth curves We would like to express our sincere appreciation to the
between the growth rate of mandibular body and condyle devoted donors of human materials, who made it possible
during the fetal period. The incremental growths of Md- to perform this study through the legally approved proce-
PGC-Sym, MdPGC-Go, and Al-Lb represent the pattern of dure from the center of Congenital Malformation, Seoul,
mandibular body growth and the incremental growths of Korea. We are very thankful to Dr. Soo Il Chung and Dr.
MdPGC-Co and Co-Go represent the pattern of condyle Yoo Mie Chung for their kind and critical review of the
growth. The former group, however, showed a slightly manuscript.
reduced growth curve compared with that of the latter
group. This may imply that condylar growth is much ac- LITERATURE CITED
celerated compared with those of the mandibular body. Azeredo RA, Watanabe I, Liberti EA, Semprini M. 1996. The arrange-
The slight reduction in gonial angle during the fetal period ment of the trabecular bone in the vestibular surface of the human
may also indicate increased growth of the condyle more in fetus mandible. I. A scanning electron microscopy study (1). Bull
a vertical than a horizontal direction. These findings are Assoc Anat (Nancy) 80:7–12.
concurrent with previous concepts of the mandibular de- Baccetti T, Franchi L, McNamara JA Jr, Tollaro I. 1997. Early dento-
velopment and growth (Baccetti et al., 1997; Bareggi et al., facial features of Class II malocclusion: a longitudinal study from
1995; Buschang et al., 1999; Keith, 1982; Kjaer 1978a,b; the deciduous through the mixed dentition. Am J Orthod Dentofa-
cial Orthop 111:502–509.
Radlanski et al., 1999; Ronning, 1995).
Bareggi R, Sandrucci MA, Baldini G, Grill V, Zweyer M, Narducci P.
In summary, we studied the sequential growth of the 1995. Mandibular growth rates in human fetal development. Arch
human fetal mandible and found that radiating trabecu- Oral Biol 40:119 –125.
lae of the mandibular body focused into a primary growth Ben-Ami Y, Lewinson D, Silbermann M. 1992. Structural character-
center, MdPGC. From the MdPGC, the mandibular devel- ization of the mandibular condyle in human fetuses: light and
opment was divided into two distinctive growth patterns electron microscopy studies. Acta Anat (Basel) 145:79 – 87.
 DEVELOPMENTAL PATTERN OF HUMAN MANDIBLE
Berraquero R, Palacios J, Gamallo C, de la Rosa P, Rodriguez JI.
1995. Prenatal growth of the human mandibular condylar cartilage.
Am J Orthod Dentofacial Orthop 108:194 –200.
Bhaskar SN, Weinmann JP, Schour I. 1953. Role of Meckels cartilage
in the development and growth of the rat mandible. J Dent Res
32:398 – 410.
Bjork A, Skieller V. 1983. Normal and abnormal growth of the man-
dible. A synthesis of longitudinal cephalometric implant studies
over a period of 25 years. Eur J Orthod 5:1– 46.
Bresin A, Kiliaridis S, Strid KG. 1999. Effect of masticatory function
on the internal bone structure in the mandible of the growing rat.
Eur J Oral Sci 107:35– 44.
Buschang PH, Santos-Pinto A, Demirjian A. 1999. Incremental
growth charts for condylar growth between 6 and 16 years of age.
Eur J Orthod 21:167–173.
Ellis Ed, Carlson DS. 1986. Histologic comparison of the costochon-
dral, sternoclavicular, and temporomandibular joints during
growth in Macaca mulatta. J Oral Maxillofac Surg 44:312–321.
Goret-Nicaise M, Dhem A. 1984. The mandibular body of the human
fetus. Histologic analysis of the basilar part. Anat Embryol 169:
231–236.
Hall BK. 1982a. How is mandibular growth controlled during devel-
opment and evolution? J Craniofac Genet Dev Biol 2:45– 49.
Hall BK. 1982b. Mandibular morphogenesis and craniofacial malfor-
mations. J Craniofac Genet Dev Biol 2:309 –322.
Ishizeki K, Saito H, Shinagawa T, Fujiwara N, Nawa T. 1999. Histo-
chemical and immunohistochemical analysis of the mechanism of
calcification of Meckels cartilage during mandible development in
rodents. J Anat 194:265–277.
Jakobsen J, Jorgensen JB, Kjaer I. 1991. Tooth and bone development
in a Danish medieval mandible with unilateral absence of the
mandibular canal. Am J Phys Anthropol 85:15–23.
Kang YK, Lee SK, Chi JG. 1992. Maxillo-mandibular development in
cerebrocostomandibular syndrome. Pediatr Pathol 12:717–724.
Keith DA. 1982. Development of the human temporomandibular joint.
Br J Oral Surg 20:217–224.
Kiliaridis S, Katsaros C. 1998. The effects of myotonic dystrophy and
Duchenne muscular dystrophy on the orofacial muscles and dento-
facial morphology. Acta Odontol Scand 56:369 –374.
Kjaer I. 1978a. Histochemical and radiologic studies of the human
fetal mandibular condyle. Scand J Dent Res 86:279 –299.
Kjaer I. 1978b. Relation between symphyseal and condylar develop-
mental stages in the human fetus. Scand J Dent Res 86:500 –502.
Kjaer I. 1997. Mandibular movements during elevation and fusion of
palatal shelves evaluated from the course of Meckels cartilage. J
Craniofac Genet Dev Biol 17:80 – 85.
Lee SK, Kim YS, Lim CY, Chi JG. 1992. Prenatal growth pattern of
the human maxilla. Acta Anat (Basel) 145:1–10.
Lee SK, Lim CY, Chi JG. 1990. Development and growth of tongue in
Korean Fetuses. Korean J Path 24:358 –374.
Lightfoot PS, German RZ. 1998. The effects of muscular dystrophy on
craniofacial growth in mice: a study of heterochrony and ontoge-
netic allometry. J Morphol 235:1–16.
Merida-Velasco JA, Sanchez-Montesinos I, Espin-Ferra J, Garcia-
Garcia JD, Roldan-Schilling V. 1993. Developmental differences in
325
the ossification process of the human corpus and ramus mandibu-
lae. Anat Rec 235:319 –324.
Morimoto K, Hashimoto N, Suetsugu T. 1987. Prenatal developmen-
tal process of human temporomandibular joint. J Prosthet Dent
57:723–730.
Ogutcen-Toller M, Juniper RP. 1993. The embryologic development of
the human lateral pterygoid muscle and its relationships with the
temporomandibular joint disc and Meckels cartilage. J Oral Maxil-
lofac Surg 51:772–779.
Orliaguet T, Darcha C, Dechelotte P, Vanneuville G. 1994. Meckels
cartilage in the human embryo and fetus. Anat Rec 238:491– 497.
Orliaguet T, Dechelotte P, Scheye T, Vanneuville G. 1993a. Relations
between Meckels cartilage and the morphogenesis of the mandible
in the human embryo. Surg Radiol Anat 15:41– 46.
Orliaguet T, Dechelotte P, Scheye T, Vanneuville G. 1993b. The rela-
tionship between Meckels cartilage and the development of the
human fetal mandible. Surg Radiol Anat 15:113–118.
Ouchi Y, Abe S, Sun-Ki R, Agematsu H, Watanabe H, Ide Y. 1998.
Attachment of the sphenomandibular ligament to bone during in-
trauterine embryo development for the control of mandibular move-
ment. Bull Tokyo Dent Coll 39:91–94.
Padwa BL, Mulliken JB, Maghen A, Kaban LB. 1998. Midfacial
growth after costochondral graft construction of the mandibular
ramus in hemifacial microsomia. J Oral Maxillofac Surg 56:122–
128.
Radlanski RJ, Lieck S, Bontschev NE. 1999. Development of the
human temporomandibular joint. Computer-aided 3D-reconstruc-
tions. Eur J Oral Sci 107:25–34.
Robertson SP, Bankier A. 1999. Oromandibular limb hypogenesis
complex (Hanhart syndrome): a severe adult phenotype [letter].
Am J Med Genet 83:427– 429.
Rodriguez-Vazquez JF, Merida-Velasco JR, Arraez-Aybar LA, Jime-
nez-Collado J. 1997a. A duplicated Meckels cartilage in a human
fetus. Anat Embryol (Berl) 195:497–502.
Rodriguez-Vazquez JF, Merida-Velasco JR, Merida-Velasco JA,
Sanchez-Montesinos I, Espin-Ferra J, Jimenez-Collado J. 1997b.
Development of Meckels cartilage in the symphyseal region in man.
Anat Rec 249:249 –254.
Ronning O. 1995. Basicranial synchondroses and the mandibular
condyle in craniofacial growth. Acta Odontol Scand 53:162–166.
Sato I, Ishikawa H, Shimada K, Ezure H, Sato T. 1994. Morphology
and analysis of the development of the human temporomandibular
joint and masticatory muscle. Acta Anat (Basel) 149:55– 62.
Shibata S, Suzuki S, Tengan T, Ishii M, Kuroda T. 1996. A histological
study of the developing condylar cartilage of the fetal mouse man-
dible using coronal sections. Arch Oral Biol 41:47–54.
Tomo S, Ogita M, Tomo I. 1997. Development of mandibular carti-
lages in the rat. Anat Rec 249:233–239.
Xu Y, Liu J, Yang M. 1983. [A study of the prenatal growth and
development of the temporomandibular joint (TMJ)]. Ssu Chuan I
Hsueh Yuan Hsueh Pao 14:1–7.
Yamazaki K, Suda N, Kuroda T. 1997. Immunohistochemical local-
ization of parathyroid hormone-related protein in developing mouse
Meckels cartilage and mandible. Arch Oral Biol 42:787–794.