Journal of craniofacial genetics and developmental biology最新文献

An attempt was made to investigate the parent-offspring similarity in the maxillofacial profile by a quantitative analysis of fingerprints. Lateral roentgenographic cephalograms and ten fingerprints were obtained from 98 Japanese patients (44 males and 54 females) and their parents. Analysis showed a significant parent-offspring correlation for both maxillofacial profile and fingerprints. The relatively low father-son correlation for both features suggests a major influence of X-linked genes. The genetic correlation between the maxillofacial profile and fingerprints was significant for parent-son but not for parent-daughter pairings. The parent-offspring correlation in the maxillofacial profile was evaluated in two groups showing differences (distant group) or similarities (near group) in the fingerprint patterns between the father and mother. In the distant group, a greater parent-offspring similarity was observed in the maxillofacial profile. The same finding was also obtained on using only digit II of the parents. Therefore, from a morphogenetical point of view, parental fingerprints appear helpful in clinical applications designed to predict maxillofacial growth in offspring.

Retinoic acid (RA) is teratogenic in many species and is an effective inducer of cleft palate in mice. The pathogenesis of cleft formation varies with the timing of exposure. It has been demonstrated, before formation of the palatal shelves, that RA exposure results in insufficient mesenchymal tissue, and palatal shelves fail to make contact. However, at the palatal shelf outgrowth stage, RA exposure affects shelf elevation and growth in rats, and possibly medial edge epithelium (MEE) differentiation in mice. The objective of this study was to examine the morphologic and functional changes associated with cleft formation in mice following exposure during shelf outgrowth. Particular emphasis was placed on evaluating the timing of palatal shelf elevation in RA exposed embryos and on identifying differentiation events occurring concurrently in the epithelium. On gestational day (GD) 12 (8:00 AM), gravid CD-1 mice were gavaged with 70 mg/kg RA or vehicle. This protocol produced a 100% incidence of cleft palate at term, allowing us to correlate the morphological and/or biochemical changes observed at pre-fusion time points. Embryos were collected at 12 hr intervals through GD 15, beginning 4 hr after exposure. Serial sections of embryos were either stained with H&E, with a battery of lectins [Sambucus nigra (SNA), Arachis hypogaea (PNA), Ricinus communis (RCA-1), Glycine max (SBA), Succinylated Wheat Germ (S-WGA)], or with a probe to hyaluronan. Throughout the period of normal palate development, the shelf mesenchyme showed increasing regional organization and progressive hydration and these changes were correlated with increase Hyaluronan (HA) deposition. RA treatment resulted in lose of regional organization and delayed mesenchyme hydration. In association with these changes there were reductions in HA deposition and extracellular matrix glycoconjugates recognized by PNA in the palate mesenchyme. Further there was a considerable delay in palatal shelf elevation and palate shelf did not make contact at the midline. Our data indicates, in embryos exposed on GD 12 to levels of RA sufficient to induce a 100% incidence of clefting, that cleft formation is a result of palatal shelves failing to make contact. Alterations in mesenchyme development and the subsequent delay in palate shelve elevation are central to RA-induced cleft formation following exposure at the palate shelf out growth stage.

It is well known that the process of branching morphogenesis requires epithelial-mesenchymal interactions. One outstanding model for the study of tissue interactions during branching morphogenesis is the embryonic mouse submandibular gland (SMG). Although it has been clearly demonstrated that the branching pattern is dependent on interactions between the epithelium and the surrounding mesenchyme, little is known about the molecular mechanism underlying the branching process. One group of transcription factors that likely participates in the control of epithelial-mesenchymal inductive interactions are the Msx-class of homeodomain-containing proteins. In this paper, we focus on Msx-2 because its developmental expression is correlated with inductive interactions, suggesting that Msx-2 may play a functional role during cell-cell interactions. We demonstrate the expression of Msx-2 mRNA and protein to be primarily in the branching epithelia with progressive embryonic (E13 to E15) SMG development and, to a lesser extent, in the mesenchyme. We also show that Msx-2 is expressed by embryonic SMG primordia cultured under defined conditions. In addition, to begin to delineate a functional role for Msx-2, we employed an experimental strategy by using exogenous glucocorticoid (CORT) treatment of embryonic SMGs in vitro and in vivo to significantly enhance branching morphogenesis and evaluate the effect of CORT treatment on embryonic SMG Msx-2 expression. A marked increase in Msx-2 transcripts and protein is detected with in vitro and in vivo CORT treatment. Our studies indicate that one mechanism of CORT regulation of salivary gland morphogenesis is likely through the modulation of Msx-2 gene expression.

The study of tooth crown variables has proven useful in the assessment of human origin and dispersal. I show that multivariate analysis of quantified total tooth structure from dental X-rays is a powerful phylogenetic methodology. From an analysis of the complex global dental phenotype ("GDP," composed of approximately 30 root, pulp, crown, and enamel variables per tooth), a representative Western European population was found to associate with Southeast Asians, while Mongolians formed a tight cluster with all Native Americans. The results suggest that either an emigrant wave, or waves, of modern humans emerged from Africa and with time segregated into at least three groups: Australian aborigines, Europeans, and Southeast Asians, or less likely due to genetic and archaeologic observations, a southern Asia origin of all modern humans from an emigrant African hominid. Both hypotheses portend an early evolution of the European genotype and support the argument that Europeans are principally derived from Upper Paleolithic hunter-gatherers, and thus Middle East Neolithic people did not have a major genetic impact on Europeans.

An artificial monozygotic twin mouse produced by bisecting a 16-cell stage embryo with a fine glass-needle and then transferring a pair of demi-embryos together into the right uterus of a pregnant recipient female mouse after a 24 hr in-vitro cultivation allowed us to examine the postnatal growth changes in monozygotic twin mice. With regard to the preimplantational growth process of the embryo, we investigated the success rate of bisecting an embryo into paired demi-embryos, the developmental ability of the bisected demi-embryo up to the early blastocyst, and the production rate of such monozygotic twin mice. The items examined in the postnatal growth process of the monozygotic twin mouse were the growth curve of the twin weight and the craniofacial size of the monozygotic twin mouse by cephalometric observations at the 3rd, 10th, 21st, 42nd, 70th, and 100th postnatal days, respectively. The following results were thus obtained. 1) The success rate of bisecting the 16-cell stage embryos into a paired demi-embryos was 86.1% (2,528/2,936). As a result, 2,301 of 2,528 paired demi-embryos could develop up to blastocysts after 24 hr of in-vitro cultivation (91.0%). 2) In addition 42 of the 394 (10.7%) recipient female mice, which had been transferred as paired demi-embryos and delivered a litter, resulted in 31 singleton mice (7.9%) or 11 paired monozygotic twin mice (2.8%), respectively. 3) The weight of each twin increased rapidly up to the 42nd day but thereafter only increased gradually up to the 100th day. The within-pair difference among each paired monozygotic twin mouse could be observed from after the 21st day until the 100th day. 4) Both the dorsoventral craniofacial size of each twin mouse and the lateral craniofacial size of each monozygotic twin mouse increased rapidly up to the 42nd day and thereafter gradually reached a plateau by the 100th day. Almost no within-pair difference was observed among each paired monozygotic twin mouse after weaning up to the 100th day. Based on these results, it is thus concluded that the craniofacial growth of each paired monozygotic twin mouse more closely resembled the growth pattern than that of the somatic growth, which thus indicated that the craniofacial growth was more greatly controlled by the genetic effect than the somatic growth. Furthermore, these findings thus suggest that an embryo bisection is an essential for producing artificial monozygotic twin mice from paired demi-embryos. Therefore, artificial monozygotic twin mice are considered to be a useful animal model for examining the effect of genetic-environment interaction on either the prenatal dento-craniofacial morphogenesis or the postnatal craniofacial growth in mice.

The in vitro protein-chemical features and the molecular background of osteogenesis imperfecta (OI), a heritable disorder of collagen I metabolism, have been elucidated in recent years. The aim of our study was to find the prevalence of dentinogenesis imperfecta (DI) and other dental anomalies in 88 patients with OI, to compare clinical with radiologic abnormalities, and to correlate these clinical/radiologic findings with the results of gel electrophoresis and molecular studies of collagen I. Twenty-eight percent of OI patients had DI. Most patients with DI had radiologic abnormalities, but some patients had radiologic signs compatible with DI, but no clinical signs of DI. OI type I patients with DI were more severely affected by OI than those without DI. In OI type III and IV, in contrast, there was no difference in overall severity between patients with and without DI. DI was not associated with any particular molecular aberration in any OI type. If defining DI from the presence of both clinical and radiologic signs, collagen I produced by cultured fibroblasts was qualitatively abnormal from all OI patients with DI. Some OI patients had dental abnormalities not resembling DI. A qualitative collagen abnormality could not be found in any of these patients. Denticles, i.e., calcifications within the pulpal cavity, were found more frequently in OI patients than in control subjects.

Diastrophic dysplasia (DTD) is a recessively inherited form of osteochondrodysplasia, presenting with disproportionate short stature and multiple orthopedic problems. The clinical oral manifestations include either cleft palate or submucous cleft palate in at least half of the patients. Histological studies have shown alterations in growth plate, articular, laryngeal, tracheal, and ear cartilages. Mutations in the DTDST gene, which codes for the sulphate transporter membrane protein, are responsible for the disease. Thirty-three patients were studied for speech characteristics and their correlation with cephalometric dimensions. Hyponasality was observed in 13 and misarticulation of /R/, /S/, or /L/ sounds in 17 of the 33 patients. Neither of these correlated with the occurrence of palatal deformities. Hyponasality was atypical and did not correlate with the obtained nasalance scores. Cephalometric measurements reflecting the size of the orofacial area of the vocal tract were short in the DTD patients compared with those in the healthy controls. The specific speech characteristics in DTD probably result from both the altered size and shape of the vocal tract and the structural and functional abnormalities of the laryngeal and tracheal cartilages.

Cranial neural crest of Xenopus laevis at different stages of development from neurulation to metamorphosis was studied for the expression of the endogenous galactoside-binding lectin of Xenopus using immunocytochemistry. The presence and localization of members of the N-CAM and cadherin cell adhesion families were also investigated. Lectin and the other known cell adhesion molecules are expressed throughout development and their localization patterns change coordinately depending on the development stage. All the molecules colocalize. The results suggest that all of these molecules, including the lectin, may be involved in cranial development, possibly in cellular adhesion.

The specific activity of GM1 ganglioside beta-galactosidase, also known as lysosomal or acidic beta-galactosidase, and the neutral beta-galactosidase were determined in the mouse three major salivary glands and compared to other tissues. Our data indicate that at pH 4.4, lysosomal beta-galactosidase activity in the submandibular gland and the sublingual gland of the mature male is the higher than in the parotid gland, kidney, and skeletal muscle. At pH 7.3, neutral beta-galactosidase activity is overall much lower and is higher in the submandibular gland compared to the sublingual and the parotid glands, kidney, and muscle. En bloc histochemical staining of tissues using x-gal as a substrate at pH 4.4 demonstrates high beta-galactosidase activity in all three salivary glands in comparison to skeletal muscle. At pH 7.3, the submandibular gland demonstrates higher activity, whereas the parotid appears negative and the sublingual gland demonstrates intermediate activity levels. En bloc staining using x-fucose (another substrate of lysosomal beta-galactosidase) demonstrates high activity in all three glands at pH 4.4, and no activity in any of the glands at pH 7.3. Microscopic histochemistry indicates that beta-galactosidase activity is localized to parenchymal cells. Thus, the two gene products for beta-galactosidase are differentially expressed in the salivary glands. These novel findings question the previous use of the bacterial beta-galactosidase (lacZ) as a reporter gene in the salivary glands. Endogenous beta-galactosidase activity in the salivary glands is probably related to glycoprotein metabolism, processing glycoconjugates containing a terminal beta-galactosidic linkage. Further studies of beta-galactosidase function and differential regulation in these tissues are needed.