Journal of craniofacial genetics and developmental biology最新文献

Osteopetrotic (op/op) mice are known to commonly show a failure of tooth eruption. It is also well understood that masticatory function is highly associated with the craniofacial morphology of the growing mouse; however, the effects on sutural growth have not been studied. The present study was conducted to examine, in detail, the morphological and histological changes of the nasopremaxillary suture in these mutant mice and to assess a role of mechanical stress from mastication in the sutural growth. The width of the nasopremaxillary suture was measured on the section for the superior (P1), middle (P2), and inferior (P3) levels. The width of the nasopremaxillary suture for the P1 level in the normal mice fed a solid diet was significantly smaller in 30-day-old mice than in 15-day-old mice, whereas the width for the level P3 was significantly greater in the 30-day-old mice than in the 15-day-old mice. These changes in the sutural space were more prominent in the normal mice fed a solid diet than in the normal mice fed a granular diet. The sutural widths for all the levels became smaller in the 30-day-old op/op mice than in the 10-day-old op/op mice. The endocranial area of the nasopremaxillary suture showed synostosis in 30-day-old op/op mice. In both the normal and op/op mice, the number of tartrate-resistant acid phosphatase (TRAP)-positive cells was greatest at the age of 15 days. Moreover, the TRAP-positive cell number was smaller in the op/op mice than in the normal mice for all the experimental stages. Since, in general, mastication begins in mice after tooth eruption, i.e. from 15 to 30 days after birth, the present findings suggest that failure of tooth eruption and the reduced masticatory function restrict sutural modification.

The parathyroid glands have been classically considered to be derivatives of the third and fourth pharyngeal pouches in most species, including humans. Furthermore, the presence of neural crest-derived cells in the parathyroid glands connective tissue has been apparently established. However, our previous studies have provided a new hypothesis on the origin of these glands in human and chick embryos. To determine the origin of the parathyroid III (P3) gland, ectoderm of the third branchial arch was cauterized in chick embryos at Hamburger and Hamilton's stage 19 (embryonic day 3). Cauterization of the ventral half of the ectoderm was followed by the non-formation, on the same side, of the P3 gland. When the dorsal half of the ectoderm was cauterized, both the right and left P3 glands formed. Our observations suggest that the ectoderm of the ventral half of the third branchial arch is necessary for the organization of the P3 gland.

This paper reports a cephalometric analysis of the craniofacial morphology in adolescents and adults with Apert syndrome. The sample comprised 26 patients with Apert syndrome (15 males and 11 females). The control group consisted of 153 adults (102 males and 51 females). Both lateral and frontal cephalograms were studied. The data were presented as mean plots of the craniofacial region together with data on some of the most significant findings. Marked differences were found in nearly all craniofacial regions except the mandible. The calvaria was increased in height and width but length was decreased. The cranial base showed marked protrusion of the greater wing of the sphenoid, which contributed to severe reduction of orbital volume and protrusion of the eyeglobe. Orbital volume was further reduced by maxillary hypoplasia in all three planes of space together with retrognathia. Maxillary height was extremely short and so was the nose. The width of the nasal cavity, height and depth of the bony nasopharynx, and the nasopharyngeal airway were all markedly reduced in size. The mandible was of fairly normal size and shape but was posteriorly inclined. Head posture was extended in relation to the cervical column. Total facial height was increased, whereas upper facial height was markedly reduced. Incisor occlusion showed mandibular overjet and open bite. Apert syndrome patients were then compared to a group of Crouzon syndrome patients. Marked and significant differences were found between the two syndromes in nearly all craniofacial regions, and craniofacial dysmorphology was generally more severe in Apert syndrome patients.

Choanal atresia may be associated with other cranio-facial malformations, including various degrees of nasal fossa malformation, and may be a part of paramedian facial clefts (as described by Tessier et al. [1977]). We identified five such cases with combined clinical elements corresponding to Tessier's paramedian facial cleft, including eyelid coloboma, mild to severe choanal and nasal fossa anomalies, ethmoidal hypoplasia and anterior skull base malformation, sometimes with proboscis lateralis and half-nose hypoplasia. These observations incited us, first, to elaborate a conception which accounts for the likely embryological mechanisms involved; second, to propose a new classification based on anatomical and pathogenic embryological considerations; and last, to propose the use of transpalatal approach to restore choanal permeability, since endonasal laser therapy is particularly dangerous in such cases.

Retinoic acid (RA) is mandatory for various biological processes and normal embryonic development but is teratogenic at high concentrations. In rodents, one of the major malformations induced by RA is cleft palate (CP). RA mediates its effects by RA receptors (RARs), but the expression patterns of RARs in the developing palate are still unclear. We investigated the normal expression of RAR alpha, beta, and gamma messenger RNAs (mRNAs) in the fetal mouse secondary palate and the effects of all-trans and 13-cis RAs on the expression of RAR mRNAs by Northern blot analysis. RAR alpha (2.8, 3.8 kb), RAR beta (3.3 kb), and RAR gamma (3.7 kb) mRNAs were detected in the fetal palate on gestational days (GD) 12.5-14.5. The expression of RAR alpha and gamma mRNAs did not show apparent sequential changes, but that of RAR beta mRNA increased at GD 13.5. Treatment of pregnant mice with 100 mg/kg all-trans RA induced CP in 94% of the fetuses and elevated the levels of RAR beta and gamma mRNAs in the fetal palate. The up-regulation of RAR beta mRNA by all-trans RA was more marked than that of RAR gamma mRNA. Treatment with 100 mg/kg 13-cis RA induced CP in only 19% of the fetuses. Although 13-cis RA elevated the RAR beta and gamma mRNA levels in fetal palates, its up-regulation was slower and less marked than that induced by all-trans RA. These findings indicate that the induction of RAR beta mRNA in the fetal palate correlates well with the tissue concentration of all-trans RA after RA treatment, and RAR beta may be one of the most influential candidate molecules for RA-induced teratogenesis.

The purpose of this study was to determine how the craniofacial morphology, evaluated from dental casts and lateral cephalograms, in individuals affected by the Marfan syndrome diverge from healthy control groups. The high and narrow palatal vault as well as maxillary and mandibular retrognathy were strongly correlated to the syndrome. About 70% of the Marfan syndrome patients (n = 76) had been referred for orthodontic treatment, mostly because of crowded teeth or extreme maxillary overjet. In 36%, the orthodontic treatment was carried out before diagnosis or suspicion about the Marfan syndrome. In comparison to healthy orthodontic patients (n = 86), selected because of presence of high and narrow palatal vaults, crowding of teeth, extreme maxillary overjet, and open bite were much more prevalent in the Marfan syndrome patients than in the orthodontic control group.

Most genetic data suggest that Australian aborigines and Southeast Asians associate, but their relative evolutionary relationship has remained obscure. Historically, the study of tooth crown variables has been important in establishing phylogenetic relationships. Through the quantification of whole tooth structure (GDP), including root, pulp, and enamel, a likely Eurasian phylogeny emerged from a canonical discriminant analysis of the microevolution among the populations. The analysis suggested that in modern human evolutionary history, Australian aborigines are the best representative extant population (first branch) from an unknown antecedent Eurasian founder population. The next branch from the Asian-based antecedent population was Caucasoids. Within the resident antecedent East Asian population, Southeast Asians then evolved, followed by a branch that lead to antecedent east Central Asians. Mongolians and all Native Americans independently evolved from this antecedent east Central Asian population. The relatively short morphogenetic separation between two areas that have been isolated for great periods of time, i.e., Australian aborigines and Native Americans, suggests that their association is not due to gene flow.

There is a well-recognized correlation between methylenetetrahydrofolate reductase (MTHFR) C677T mutation homozygosity, elevated plasma homocysteine, and increased risk of neural tube defects (NTDs). This risk is modulated by maternal and fetal folate levels provided provided by diet or supplement. Although the frequencies of the C677T mutation are nearly identical between north and south China, the incidence of NTDs is nearly 5 times greater in the north than in the south. This dramatic difference appears related to the fact that dietary sources of folate are more plentiful and varied in South China.

Human craniofacial morphogenesis is a complex biological event: it is mediated by several factors and different types tissue interaction. Recent studies on animal models have led to an improved understanding of human craniofacial malformations. In particular, the endothelins, peptides that are involved in various biological functions in many tissues and organs, have been shown to play a crucial role in the development of the first branchial-arch-derived structures in mice [Kurihara et al., Nature 368:703-710, 1994]. We previously reported the identification and localization of endothelin-1 (ET-1) and its receptors in human fetal jaw [Barni et al., Dev Biol 168:373-377, 1995]. In the present study, the gene expression of ET-1 and its receptors were demonstrated in human jaw from 11-12-week-old fetuses. By using in situ hybridization, mRNA for ET-1 was localized in the epithelial cells of the oral mucosa: mRNA for ET receptors (ETA and ETB subtypes) was expressed in the mesenchyme. In situ binding experiments confirmed the presence of ETA and ETB receptors in the cells involved in the osteogenesis of the mandible. Furthermore, ET-1 was able to stimulate thymidine uptake and the expression of the oncoprotein c-fos in the same cell types. Our results indicate that ET-1 may play a putative role in epithelium-mesenchyme interaction during human craniofacial morphogenesis. Our findings are in complete accord with those of the most recent works by Yanagisawa [Yanagisawa H et al., 1998] and Clouthier [Clouthier et al., Development 125:813-824, 1998]. They most probably confirm the primary role of ET-1 in the development of the pharyngeal arches.

Abnormal craniofacial features of a transgenic mouse model of chondrodysplasia with a type II collagen mutation (Gly574Ser) are described in this report. In addition to a shortened mandible and cleft palate, a misshapen otic capsule was observed. Interestingly, hearing impairment is often a component of the chondrodysplasia phenotype that results from mutations in COL2A1. To identify a potential mechanism in the hearing loss associated with type II collagen mutations, we examined the development of the otic capsule in the transgenic mice. It appeared to be smaller overall, relative to the skull proportions, and rather than the normal rounded dimensions, the transgenic capsule was flattened and elongated. We speculate that the cartilage of the developing otic capsule was less able to resist the mechanical forces from the developing brain and other tissues within the cranium and thus became deformed under pressure. We further speculate that the hearing loss associated with the chondrodysplasia phenotype is at least partially due to these defects in the developing cartilage matrix of the otic capsule.