Barni T, Fantoni G, Gloria L, Maggi M, Peri A, Balsi E, Grappone C, Vannelli G B
Department of Human Anatomy and Istology, University of Florence, Italy.
J Craniofac Genet Dev Biol. 1998 Oct-Dec;18(4):183-94.
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.
它由多种因素和不同类型组织间的相互作用介导。近期对动物模型的研究增进了我们对人类颅面畸形的理解。特别是内皮素，这种参与许多组织和器官多种生物学功能的肽，已被证明在小鼠第一鳃弓衍生结构的发育中起关键作用[栗原等人，《自然》368:703 - 710，1994]。我们之前报道了内皮素 - 1（ET - 1）及其受体在人胎儿颌骨中的鉴定和定位[巴尔尼等人，《发育生物学》168:373 - 377，1995]。在本研究中，ET - 1及其受体的基因表达在11 - 12周龄胎儿的人颌骨中得到证实。通过原位杂交，ET - 1的mRNA定位于口腔黏膜的上皮细胞中：ET受体（ETA和ETB亚型）的mRNA在间充质中表达。原位结合实验证实了参与下颌骨成骨的细胞中存在ETA和ETB受体。此外，ET - 1能够刺激相同细胞类型中胸苷摄取和癌蛋白c - fos的表达。我们的结果表明，ET - 1可能在人类颅面形态发生过程中的上皮 - 间充质相互作用中发挥假定作用。我们的发现与柳泽[柳泽H等人，1998]和克劳蒂尔[克劳蒂尔等人，《发育》125:813 - 824，1998]的最新研究结果完全一致。它们很可能证实了ET - 1在咽弓发育中的主要作用。
