Cellular and cis-regulation of En-2 expression in the mandibular arch.

Investigations into early muscle development have focused primarily on somite derived cells. Cranial mesoderm does not undergo somitogenesis, and muscle formation in this region is less well understood. In the present study, we have focused upon the expression of engrailed in mandibular arch myoblasts. We demonstrate that En-2 is expressed in mandibular arch myoblasts of the mouse. The activity of the En-2 enhancer is maintained in several functionally related muscles that arise from the first arch. Through the use of reporter transgenics, we demonstrate that local cell-cell interactions are important in maintaining En-2 expression in the mandibular arch cells. En-2 enhancer activity in the first arch requires a combination of cis-acting sequences that includes a motif which is identical to one found in the Otx2 enhancer and which is sufficient to direct expression in the first arch. These data support the notion that cranial muscle development is regulated by local cell-cell interactions which distinguish distinct anatomical and functional muscle groups.     

Tooth and bone development in a Danish medieval mandible with unilateral absence of the mandibular canal.

A Danish anthropological collection of medieval human skeletons excavated in 1986 involves a mandible (No. 212) from an adult female born without the lower alveolar nerve and mandibular canal. It is believed that the defect has resulted in lack of tooth development on the affected side and that the mylohyoid nerve has partially compensated for this defect by development of teeth in localized areas. The defective mandibular dentition has caused a compensatory development of the alveolar process in the maxilla. The missing occlusal support has altered muscular traction on the mandible. This has caused an alteration in mandibular shape. Whether the asymmetric development of the mandible is caused by muscular dysfunction, by failure in angular growth apposition, or by a combination of these factors is discussed. The case presents valuable data in the ongoing discussion about the interaction between nerve tissue and tooth formation and about the interaction between occlusion, jaw morphology, and muscular traction. The study shows how archeological material in an interdisciplinary cooperation between archeological, embryological and orthodontic research can contribute to the clarification of current biological problems.     

Epithelial-mesenchymal interactions in the outgrowth of limb buds and facial primordia in chick embryos.

The facial primordia in the chick embryo begin as rounded swellings that surround the primitive mouth and these grow out to form the beak. The control of proximodistal outgrowth is not well understood but may involve similar mechanisms to the limb bud. In order to test this hypothesis, combinations were made between epithelium and mesenchyme from facial primordia and limb buds. Signals from all three types of facial mesenchyme (frontonasal mass, mandibular, and maxillary) maintained the thickened apical ectodermal ridge of limb epithelium for up to 48 h. Combinations of tissues from the frontonasal mass mesenchyme and limb epithelium underwent substantial and correct morphogenesis. In contrast, poor development was observed in combinations with mandibular mesenchyme. Signals from frontonasal mass epithelium promoted outgrowth and morphogenesis of limb mesenchyme whereas mandibular and maxillary epithelium did not support joint morphogenesis. The results suggest that signals employed in the epithelial-mesenchymal interactions in facial primordia are similar but not identical to those signals used in the limb bud.     

中华蜜蜂上颚腺的组织结构及其胚后发育

【目的】上颚腺（mandibular gland）是昆虫重要的外分泌腺,它产生的化学物质在昆虫的种内信息交流中起重要的作用。本研究目的在于了解中华蜜蜂Apis cerana cerana上颚腺的组织结构以及胚后发育特点。【方法】本研究通过组织形态学、BrdU免疫组织化学等技术,对中华蜜蜂上颚腺的结构和发育过程进行了比较研究。【结果】中华蜜蜂的上颚腺在不同级型间差异显著,蜂王的面积最大,工蜂较小,而雄蜂退化。上颚腺出现在末龄幼虫到预蛹阶段,细胞分裂活动的高峰期发生在蛹发育的第1天,随后分裂细胞数减少,并一直持续到蛹发育的第6天结束。在上颚腺发育早期,由分泌细胞分化的内膜就已经出现,并一直保持到成虫。【结论】本研究为昆虫上颚腺的发育和功能研究提供了理论基础。     

Firing activities of neurosecretory cells producing diapause hormone and its related peptides in the female silkmoth,Bombyx mori. II. mandibular and maxillary cells

A gene encoding a precursor polyprotein of diapause hormone (DH) and four related peptides is expressed by three groups of neurosecretory cells in the suboesophageal ganglion (SOG) of Bombyx mori. Long-term chronic recordings of firing activities were made from a common axonal tract (the maxillary nerve) of two groups of cells localized in the mandibular and maxillary neuromeres of SOG during pupal-adult development. Mandibular and maxillary cells usually produced a cluster of action potentials at an interval of 30-60 min during pupal-adult development and there was no significant difference in the firing activity profile between diapause-egg and non-diapause-egg producers. We suggest that rather than DH secretion, pupal mandibular and maxillary cells are involved in the secretion of DH-related neuropeptides. DH secretion seems to be assigned to the third group of cells (labial cells); hence, there may be different posttranslational processing of the precursor polyprotein in different neurosecretory cell groups.     

Mandibular precedence in the prenatal development of four permanent teeth.

As shown in 62 pairs of dental opponents from 32 grossly normal human fetuses in the 75-378 mm crown-rump range, mandibular precedence is the rule for 11, 12, C and M1, a trend in agreement with mandibular precedence for deciduous teeth through dm1 and in the gingival emergence of the same permanent teeth during postnatal development.     

The role of effectors of the activin signalling pathway, activin receptors IIA and IIB, and Smad2, in patterning of tooth development.

The gene for activin betaA is expressed in the early odontogenic mesenchyme of all murine teeth but mutant mice show a patterning defect where incisors and mandibular molars fail to develop but maxillary molars develop normally. In order to understand why maxillary molar tooth development can proceed in the absence of activin, we have explored the role of mediators of activin signalling in tooth development. Analysis of tooth development in activin receptor II and Smad2 mutants shows that a similar tooth phenotype to activin betaA mutants can be observed. In addition, we identify a novel downstream target of activin signalling, the Iroquois-related homeobox gene, Irx1, and show that its expression in activin betaA mutant embryos is lost in all tooth germs, including the maxillary molars. These results strongly suggest that other transforming growth factor beta molecules are not stimulating the activin signalling pathway in the absence of activin. This was confirmed by a non-genetic approach using exogenous soluble receptors to inhibit all activin signalling in tooth development, which reproduced the genetic phenotypes. Activin, thus, has an essential role in early development of incisor and mandibular molar teeth but this pathway is not required for development of maxillary molars.     

Development and size of the teeth of Macaca mulatta.

A cross-sectional sample of 151 skulls from Macaca mulatta of known age and similar rearing in U.S. Primate Centers was analyzed to determine age-related "norms" of stages of development and size of teeth. The stages of development from the follicle of a deciduous incisor in the fetus to completion of the root with apex closed of the permanent third molar were related to age. The age range observed for eruption of each tooth was noted and related to its stage of development. The crown of each erupted tooth was found to be completely developed, but growth of its root continued for a longer, indeterminate period. When a deciduous tooth was exfoliated, the crown of the permanent successor was found to be completed and root growth had begun. Measurements of both mesiodistal and faciolingual diameters and of crown length of the teeth in situ and of total length and root length on roentgenograms were examined for sexual dimorphism. The faciolingual diameter of the deciduous mandibular second incisor and of both second molars showed the greatest sexual dimorphism among both diameters of all deciduous teeth. The mesiodistal and faciolingual diameters of the mandibular premolars were found to be the best dimensions in discriminant functions for identifying sex in the absence of permanent canines.     

The post-embryonic changes in Melipona quadrifasciata anthidioides Lep. (Hym. Apoidea). II. Development of the salivary glands system

The paper deals with the development of the salivary gland system in Melipona quadrifasciata anthidioides, which begins in the prepupal stage. The silk glands degenerate by autolysis at the end of the larval stage. Degeneration is characterized by cytoplasmic vacuolization and pycnosis of the nuclei of the secretory cells. The glandular secretory portion of degenerated silk glands separates from the excretory ducts. The salivary glands develop from the duct of the larval silk glands. The thoracic salivary glands develop from the ducts of the secretory tubules and the head salivary glands from the terminal excretory duct. The mandibular glands appear in the prepupa as invaginations of mandibular segments, and their differentiation to attain the adult configuration occurs during pupation. The hypopharyngeal glands have their origin from evaginations of the ventral anterior portion of the pharynx. A long tubule first appears with walls formed by more than one cellular layer. Then some cells separate from the lumen of the duct, staying attached to it by a cuticular channel in part intracellular. The initial duct constitutes the axial duct, in which the channel of the secretory cells opens. During the development of salivary and mandibular glands, they recapitulate primitive stages of the phylogeny of the bees. During the development of salivary glands system, mitosis accounts for only part of the growth. Most of the growth occurs by increase in size of cells rather than by cell division. In brown-eyed and pigmented pupae six days before emergence, the salivary gland system is completely developed, although not yet functioning.     

Correlation between mandibular retrognathia and induction of cleft palate with 6-aminonicotinamide in the rat.

A single injection of the niacin antimetabolite 6-aminonicotinamide (6-AN) late in gestation produces cleft palate in the rat. In order to achieve an understanding of the mechanism of induction of cleft palate, craniofacial growth and palate development were studied in Sprague-Dawley rats after treatment with 6-AN on day 15 of gestation. The rats were maintained on a high niacin diet (95 ppm) and subjected to three different teratogenic levels of 6-AN. The first group was injected with 8 mg/kg, the second was fasted and injected with 8 mg/kg and the third was treated with 16 mg/kg. The lowest teratogenic dose, 8 mg/kg, produced mild mandibular retrognathia on day 16, delayed shelf elevation a few hours and resulted in small rostral and small caudal clefts of the secondary palate. The moderate dose, 8 mg/kg with fasting, produced more severe mandibular retrognathia, delayed shelf elevation about 24 hours and resulted in 37% full clefts and 63% partial clefts of the palate. The highest teratogenic dose, 16 mg/kg, produced severe mandibular retrognathia, delayed shelf elevation by more than 24 hours and resulted in 100% full clefts of the palate. In each 6-AN group, the most severe mandibular retrognathia was present between days 16 and 17, the critical time for palate closure in the rat. Treatment with 6-AN also produced abnormality of the epithelial cells of the palate, the toothbuds and the nasal septum. Molar and incisor toothbuds were small and malformed, and the epithelial surfaces of the palate and the soft tissue nasal septum did not fuse.     

Mandibular function in Galago crassicaudatus and Macaca fascicularis: an in vivo approach to stress analysis of the mandible.

Single-element and/or rosette strain gages were bonded to mandibular cortical bone in Galago crassicaudatus and Macaca fascicularis. Five galago and eleven macaque bone strain experiments were performed and analyzed. In vivo bone strain was recorded from the lateral surface of the mandibular corpus below the postcanine tooth row during transducer biting and during mastication and ingestion of food objects. In macaques and galagos, the mandibular corpus on the balancing side is primarily bent in the sagittal plane during mastication and is both twisted about its long axis and bent in the sagittal plane during transducer biting. On the working side, it is primarily twisted about its long axis and directly sheared perpendicular to its long axis, and portions of it are bent in the sagittal plane during mastication and molar transducer biting. In macaques, the mandibular corpus on each side is primarily bent in the sagittal plane and twisted during incisal transducer biting and ingestion of food objects, and it is transversely bent and slightly twisted during jaw opening. Since galagos usually refused to bite the transducer or food objects with their incisors, an adequate characterization of mandibular stress patterns during these behaviors was not possible. In galagos the mandibular corpus experiences very little transverse bending stress during jaw opening, perhaps in part due to its unfused mandibular symphysis. Marked differences in the patterns of mandibular bone strain were present between galagos and macaques during the masticatory power stroke and during transducer biting. Galagos consistently had much more strain on the working side of the mandibular corpus than on the balancing side. These experiments support the hypothesis that galagos, in contrast to macaques, employ a larger amount of working-side muscle force relative to the balancing-side muscle force during unilateral biting and mastication, and that the fused mandibular symphysis is an adaption to use a maximal amount of balancing-side muscle force during unilateral biting and mastication. These experiments also demonstrate the effects that rosette position, bite force magnitudes, and types of food eaten have on recorded mandibular strain patterns.     

Early embryonic mouse mandibular morphogenesis and cytodifferentiation in serumless, chemically defined medium: a model for studies of autocrine and/or paracrine regulatory factors

During craniofacial and mandibular development at least three interdependent processes become integrated: 1) regulation of time-dependent differential gene expression; 2) positional information resulting in pattern formations; and 3) morphogenesis. The present studies were designed to test the hypothesis that intrinsic and/or paracrine factors regulate the developmental program for embryonic mouse mandibular morphogenesis, histogenesis, and cytodifferentiation. Either E11 or E12 C57B110 (B10.A) strain mouse mandibular processes were cultured in serumless, chemically defined medium for periods up to 9 days in vitro. At selected stages of development 3H-thymidine incorporation into DNA was used to evaluate the mitotic labeling for selected tissue compartments. Macroscopic observations demonstrated that morphogenesis (shape/form) in vitro was comparable to that for in vivo controls. Histological results demonstrated that chondrogenesis, osteogenesis, tooth formation, tongue formation, lip formation, and epithelial differentiation with keratinization were expressed according to sequence, time, and positions comparable to those observed in controls. This experimental approach provided datasets to support the hypothesis that exogenous long-range factors are not required for embryonic mouse mandibular morphogenesis and further suggested that autocrine and/or paracrine factors mediate the timing and position of mandibular development.     

The role of TGF-beta signaling in regulating chondrogenesis and osteogenesis during mandibular development

During craniofacial development, Meckel's cartilage and the mandible bone derive from the first branchial arch, and their development depends upon the contribution of cranial neural crest (CNC) cells. We previously demonstrated that conditional inactivation of Tgfbr2 in the neural crest of mice (Tgfbr2^fl/fl;Wnt1-Cre) results in severe defects in mandibular development, although the specific cellular and molecular mechanisms by which TGF-β signaling regulates the fate of CNC cells during mandibular development remain unknown. We show here that loss of Tgfbr2 does not affect the migration of CNC cells during mandibular development. TGF-β signaling is specifically required for cell proliferation in Meckel's cartilage and the mandibular anlagen and for the formation of the coronoid, condyle and angular processes. TGF-β-mediated connective tissue growth factor (CTGF) signaling is critical for CNC cell proliferation. Exogenous CTGF rescues the cell proliferation defect in Meckel's cartilage of Tgfbr2^fl/fl;Wnt1-Cre mutants, demonstrating the biological significance of this signaling cascade in chondrogenesis during mandibular development. Furthermore, TGF-β signaling controls Msx1 expression to regulate mandibular osteogenesis as Msx1 expression is significantly reduced in Tgfbr2^fl/fl;Wnt1-Cre mutants. Collectively, our data suggest that there are differential signal cascades in response to TGF-β to control chondrogenesis and osteogenesis during mandibular development.     

Development of head and trunk mesoderm in the dogfish,Scyliorhinus torazame: I. Embryology and morphology of the head cavities and related structures

Vertebrate head segmentation has attracted the attention of comparative and evolutionary morphologists for centuries, given its importance for understanding the developmental body plan of vertebrates and its evolutionary origin. In particular, the segmentation of the mesoderm is central to the problem. The shark embryo has provided a canonical morphological scheme of the head, with its epithelialized coelomic cavities (head cavities), which have often been regarded as head somites. To understand the evolutionary significance of the head cavities, the embryonic development of the mesoderm was investigated at the morphological and histological levels in the shark, Scyliorhinus torazame. Unlike somites and some enterocoelic mesodermal components in other vertebrates, the head cavities in S. torazame appeared as irregular cyst(s) in the originally unsegmented mesenchymal head mesoderm, and not via segmentation of an undivided coelom. The mandibular cavity appeared first in the paraxial part of the mandibular mesoderm, followed by the hyoid cavity, and the premandibular cavity was the last to form. The prechordal plate was recognized as a rhomboid roof of the preoral gut, continuous with the rostral notochord, and was divided anteroposteriorly into two parts by the growth of the hypothalamic primordium. Of those, the posterior part was likely to differentiate into the premandibular cavity, and the anterior part disappeared later. The head cavities and somites in the trunk exhibited significant differences, in terms of histological appearance and timing of differentiation. The mandibular cavity developed a rostral process secondarily; its homology to the anterior cavity reported in some elasmobranch embryos is discussed.     

Differences in the extent and heterogeneity of lysyl hydroxylation in embryonic chick cranial and long bone collagens

The hydroxylation of lysine in embryonic chick long bone and mandibular collagen was found to be approximately 3-fold greater than that of the collagens of adult animals. In contrast, no significant difference was found in extent of lysine hydroxylation of the collagens of frontal bones of embryos and postnatal animals. Both histochemical and biochemical evidence established that full thickness diaphyseal bone samples contained cartilage and, consequently, type II collagen which undoubtedly contributed to the higher hydroxylysine contents of young postnatal animals reported previously. DEAE ion exchange chromatography of the alpha 1(I) chains of lathyritic long bone and mandibular collagens isolated by carboxymethyl-cellulose ion exchange chromatography showed considerable heterogeneity, whereas the alpha 1(I) chains obtained from lathyritic frontal bone collagen did not. Three fractions of alpha 1(I) chains of long bones and mandibular collagen were isolated which differed significantly in their hydroxylysine contents. The relative proportion of the three peaks changed as a function of embryonic age and maturation: more of the alpha 1(I) chains with the highest hydroxylysine content was present in the collagen synthesized earliest during embryonic development. This is consistent with results which demonstrated that the collagens synthesized earliest during embryonic and postnatal development had the highest hydroxylysine contents.     

Mandibular Shape, Ontogeny and Dental Development in Bonobos (Pan paniscus) and Chimpanzees (Pan troglodytes)

The postnatal ontogenetic patterns and processes that underlie species differences in African ape adult mandibular morphology are not well understood and there is ongoing debate about whether African ape faces and mandibles develop via divergent or parallel trajectories of shape change. Using three-dimensional (3D) morphometric data, we first tested when in postnatal development differences in mandibular shape are initially evident between sister species Pan troglodytes and P. paniscus. Next, we tested whether each species has a distinct and non-parallel trajectory of mandibular development. Mandibles sampled across a broad developmental range of wildshot bonobos (n = 44) and chimpanzees (n = 59) were radiographed and aged from their dental development. We then collected 3D landmark surface data from all the mandibles. A geometric morphometric analysis of size-corrected 3D data found that bonobos and chimpanzees had parallel and linear ontogenetic trajectories of mandibular shape change. In contrast, mandibular shape was statistically different between P. paniscus and P. troglodytes as early as infancy, suggesting that species shape differences are already established near or before birth. A linear and stable trajectory of shape change suggests that mandibular ontogeny in these apes is unimpacted by non-linear variation in tooth developmental timing.     

Serial homology of the mandible and maxilla in the jumping bristletail Pedetontus unimaculatus Machida, based on external embryology (Hexapoda: Archaeognatha, Machilidae)

The development of the mandible and maxilla is examined with the scanning electron microscope in the Archaeognatha. Serial homology is discussed to elucidate the general construction of the hexapod mandible. The part comparable to the maxillary palp does not develop in the mandible. Thus, the mandible is coxopodal in origin, and not telognathic but coxognathic. The mandible proper is subdivided into two in late embryonic development, and the smaller proximal and larger distal parts are homologized with the maxillary cardo and stipes, respectively, being subcoxal and coxal in nature. The partition into the "mandibular cardo" in which the mandibular monocondyle is formed and the "mandibular stipes" is recognized as a cuticular ridge or the "mandibular basal ridge" in the postembryonic stages including the imaginal. The molar and incisor are comparable in position and homologized with the maxillary lacinia and galea, respectively. The lacinia and galea could be morphologically interpreted as being the endites of the maxillary coxae I and II, respectively, and the molar and incisor might represent the mandibular coxae I and II as their constituents or endites.     

Localization of CD44 (hyaluronan receptor) and hyaluronan in rat mandibular condyle.

CD44 is a multifunctional adhesion molecule that binds to hyaluronan (HA), type I collagen, and fibronectin. We investigated localization of CD44 and HA in mandibular condylar cartilage compared with the growth plate and the articular cartilage, to clarify the characteristics of chondrocytes. We also performed Western blotting using a lysate of mandibular condyle. In mandibular condyle, CD44-positive cells were seen in the surface region of the fibrous cell layer and in the proliferative cell layer. Western blotting revealed that the molecular weight of CD44 in condyle was 78 to 86 kD. Intense reactivity for HA was detected on the surface of the condyle and the lacunae of the hypertrophic cell layer. Moderate labeling was seen in cartilage matrix of the proliferative and maturative layer. Weak labeling was also seen in the fibrous cell layer. In growth plate and articular cartilage, HA was detected in all cell layers. However, chondrocytes of these cartilages did not exhibit reactivity for CD44. These results suggest that chondrocytes in the mandibular condylar cartilage differ in expression of CD44 from those in tibial growth plate and articular cartilage. Cell-matrix interaction between CD44 and HA may play an important role in the proliferation of chondrocytes in the mandibular condyle.     

Fate of recombinants of the rat mandibular epithelium with cranial ectomesenchymal cells of different sources in vitro

The recombinants of the mandibular molar bud epithelia with cranial ectomesenchymal cell groups from several different sources--mandibular molar area, tongue anlagen, and lateral nasal process--were cultured. Dental laminalike buds were developed in each of the recombinants (incidence of development 38-86%). In the heterotrophic recombinants, heterotypic differentiation of mandibular epithelium was also induced. However, the foreign ectomesenchymal cells were not induced heterotypically by the epithelial genetic factor, but the mesenchymal genetic factor is maintained. It is suggested that mandibular molar bud epithelia have potency to proliferate into mesenchyme under non-organ-specific influences of ectomesenchymal cells and that presumptive mandibular mucosal epithelia have multipotency for differentiation sensitive to inductive influences by the heterotypic cranial ectomesenchymal cells but that the mandibular molar bud epithelia have no heterotypic inductive activity for the differentiation of cranial ectomesenchymal cells.     

Age-related changes in microarchitecture and mineralization of cancellous bone in the porcine mandibular condyle

The mandibular condyle is considered a good model for developing cancellous bone because of its rapid growth and high rate of remodeling. The aim of the present study was to analyze the simultaneous changes in microarchitecture and mineralization of cancellous bone during development in a three-dimensional fashion. Eight mandibular condyles of pigs aged 8 weeks prepartum to 108 weeks postpartum were scanned using microCT with an isotropic spatial resolution of 10 microm. The number of trabeculae decreased during development, whereas both the trabecular thickness and the distance between the trabeculae increased. The bone surface to volume ratio decreased during development, possibly limiting the amount of (re)modeling. Both the mean degree of mineralization and intratrabecular differences in mineralization between the surfaces and cores of trabecular elements increased during development. The trabecular surfaces were more highly mineralized in the older condyles compared to the younger ones. Together with the observed decrease in the relative size of trabecular surface, this finding suggests a decrease in (re)modeling activity during development. In accordance with the general growth and development of the pig, it was concluded that most developmental changes in cancellous bone occur until the age of 40 weeks postpartum.