Journal of craniofacial genetics and developmental biology最新文献

The formation of the midbrain region depends mainly on the activity of a signalling center located in the isthmus region, on the border between the prospective mesencephalon and metencephalon. FGF-8 has been proposed as a signalling molecule responsible for this specification because of its expression pattern and its ability to elicit duplication of the midbrain region when expressed ectopically in the neuroepithelium. Here we present evidence that members of the FGF family of growth factors when released in the cephalic mesenchyme are able to extend the expression of the mesencephalic marker En-2 to both the anterior and the posterior regions of its original landmark. This alteration in the expression pattern of En-2 is not accompanied by a significant alteration in the later development of the midbrain-cerebellar anlage, although the eye development is severely altered. Members of the bone morphogenetic protein family ectopically released from the mesenchyme down-regulate the expression of En-2 and also have an effect on the development of the eye. These results demonstrate that growth factor molecules produced in the mesenchyme (vertical signalling) participate in the correct establishment of the antero-posterior patterning of the cephalic nervous system during development.

Molecular aspects of bone formation and bone growth are discussed together with selected genetic disorders of the involved genes. Topics covered include: collagenopathies and osteogenesis imperfecta; core binding factor transcription factors and cleidocranial dysplasia; bone morphogenetic proteins and fibrodysplasia ossificans progressiva; transforming growth factor beta, suture closure, and craniosynostosis; Indian hedgehog, parathyroid hormone-related protein together with its receptor, and Jansen metaphyseal chondrodysplasia.

Exquisite control of chondrocyte function in the zone of hypertrophy results in expansive growth of cartilaginous growth plates, and is a prerequisite for normal skeletal lengthening. We hypothesize that hyaluronan-mediated hydrostatic pressure causes lacunae expansion in the zone of hypertrophy; an important mechanism in cartilaginous growth plate and associated skeletal expansion. The role of hyaluronan and CD44 in this mechanism was studied using organ culture of the bipolar cranial base synchondroses. Hyaluronan was present in the hypertrophic zones, pericellular to the hypertrophic chondrocytes, while no hyaluronan was detected in the resting, proliferating and maturing zones. This localization of hyaluronan was associated with increased lacunae size, suggesting that chondrocytes deposit and retain pericellular hyaluronan as they mature. In comparison, Toluidine Blue staining was associated with the territorial matrix. Hyaluronidase, the hyaluronan-degrading enzyme, and CD44, the receptor for hyaluronan which also participates in the uptake and degradation of hyaluronan, were co-localized within the zone of ossification. This pattern of expression suggests that cells in the early zone of ossification internalize and degrade hyaluronan through a CD44-mediated mechanism. Treatment of the cultured segments with either Streptomyces hyaluronidase or hyaluronan hexasaccharides inhibited lacunae expansion. These observations demonstrate that hyaluronan-mediated mechanisms play an important role in controlling normal skeletal lengthening.

Skeletogenesis and chondrogenesis result from a sequence of events involving epithelial-mesenchymal interaction, condensation, and differentiation. Types of bone and cartilage formation include: (1) intramembranous ossification, (2) endochondral ossification, (3) combined endochondral and intramembranous ossification, (4) heterotopic bone and cartilage formation, and (5) secondary cartilage formation. Pathologic conditions with bone and cartilage include: (1) benign and malignant tumors and (2) reactive osseous and cartilaginous metaplasia.

Glucosyltransferase from oral bacteria Streptococcus mutans is the most significant virulent factor in causing dental caries. The enzyme has two subsites. The binding specificity of divalent metal ions to glucosyl or fructosyl subsite was examined using multiple inhibition kinetics. The interaction factor "alpha" identifies whether the two subsites are exclusive or non-exclusive.

It is well known that the defect in bone resorption in osteopetrotic (op/op) mice brings about deformation of the cranium and failure of tooth eruption. However, the influences on longitudinal growth of the craniofacial skeleton have not been elucidated. This study was thus conducted to examine craniofacial morphology and longitudinal changes in the op/op mice by means of morphometric analysis with lateral cephalograms. Lateral cephalograms, taken every 10 days from 10- to 90-day-old mice, were analyzed on a personal computer for 11 measurement items. For the nasal bone region, the most prominent differences were found between the op/op and normal mice. The anterior cranial base and occipital bone height presented almost equivalent growth changes in both the op/op and normal mice. The size of mandible, meanwhile, was significantly smaller in the op/op mice than in the normal controls. The gonial angle was also significantly larger in the op/op mice than in the normal mice throughout the experimental period. Thus, substantial differences in craniofacial growth were demonstrated in various areas of the craniofacial complex, which are assumed essentially due to the lack of osteoclastic bone resorption during growing period. Since the difference became more prominent in the anatomic regions relevant to the masticatory functions, it would be a reasonable assumption that reduced masticatory function is also a key determinant for the less-developed craniofacial skeleton in the op/op mouse.

Fifty microliters of ethanol diluted in 50 microl of distilled water were injected into the air chamber of chick eggs immediately before their incubation, and modifications in a series of parameters were recorded. The somatic weight of the ethanol-treated embryos was lower compared with control and vehicle-administered embryos during days 13, 15, 17, and 19 of incubation, but was the same on day 21. The brain weight was lower in the ethanol-treated embryos on all the days studied (days 13, 15, 17, 19, and 21 of incubation). Skull measurements showed that the transverse anteroposterior and sagittal diameters were significantly smaller in ethanol-treated embryos compared with control and vehicle-administered embryos on days 17, 19, and 21 of incubation.

The spheno-ethmoidal model of midfacial retrognathia suggests that deficient chondrocytic proliferation in the anterior cranial base is associated with inadequate anterior translation of the midfacial complex resulting, for example, in Class III malocclusions. The purpose of this study was to determine whether the morphology of the midface differed in subjects of diverse ethnic origin exhibiting features associated with Class III malocclusions. Lateral cephalographs of 142 children of Korean or European American descent aged between 5 and 11 years were compared. The cephalographs were traced and subdivided into seven age- and sex-matched groups. Average geometries, scaled to an equivalent size, were generated using Procrustes superimposition and subjected to analysis of variance (ANOVA). Graphical analysis using a color-coded finite-element scaling analysis (FESA) program was used to localize differences in morphology. Results indicated that the mean Korean and European American midfacial configurations differed statistically (P < 0.01), and this difference was maintained at most, but not all, age-wise comparisons. Comparing Korean and European American Class III midfacial configurations for local size-change, FESA analysis revealed that while local increases in size were apparent in the posterior palatal regions, the Korean anterior nasal spine regions were generally smaller. For shape-change, the Korean and European American midfacial configurations were predominantly isotropic. Therefore, heterogeneity in appearance may be influenced by morphological variation of the midfacial complex in subjects of diverse ethnic origin, but features of the anterior cranial base may contribute also to the prevalence and severity of Class III malocclusions in Koreans. Moreover, perturbations in endochondral mechanisms of cranio-mandibular growth, and not maxillary intramembranous methods, may be implicated in the etiology of Class III malocclusions in South East Asians.

Protein kinase C (PKC) plays a critical role in signal transduction, mediating various cellular events critical for normal development, including that of the palate. In vivo and in vitro studies suggest the relevance of the inhibition of PKC by the mycotoxin, secalonic acid D (SAD), to its induction of cleft palate (CP) in mice. In the present study, temporal and spatial expression and the activity of various PKC isoenzymes were studied in the control and SAD-exposed murine embryonic palate during gestational days (GD) 12-14.5 by western blotting, immunohistochemistry, and phosphotransfer assay. The Ca2+-dependent isoenzymes, PKC alpha and PKC betaII, showed significant expression on GD 12.0, which gradually decreased through GD 14.5, whereas PKC betaI and PKC gamma were negligible throughout. All Ca2+-independent isoenzymes (epsilon, delta, and zeta) were expressed more abundantly and, in contrast to the Ca2+-dependent ones, progressively increased with age. SAD failed to alter this pattern of expression but enhanced the phosphorylation of PKC epsilon throughout development. Immunohistochemical analysis revealed an isoenzyme-specific distribution of PKC between the epithelium and mesenchyme. As expected, SAD significantly inhibited the total Ca2+-dependent PKC activity in palatal extracts. Although total Ca2+-independent PKC activity in palatal extracts was unaffected by SAD, individual pure isoenzymes were either selectively inhibited (PKC zeta), stimulated (PKC delta), or unaffected (PKC epsilon) by SAD. These results show that PKC isoenzymes exhibit dynamic temporal and spatial patterns of expression and activity in the developing palate and that the induction of CP by SAD is associated with an alteration in their activation and/or activity.