Role of endothelin in the human craniofacial morphogenesis

Human craniofacial morphogenesis is a complex biological event: it is media ted by several factors and different types tissue interaction. Recent studi es on animal models have led to an improved understanding of human craniofa cial malformations. In particular, the endothelins, peptides that are invol ved in various biological functions in many tissues and organs, have been s hown 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-l (ET -1) and its receptors in human fetal jaw [Barni et al., Dev Biol 168:373-37 7, 1995]. In the present study, the gene expression of ET-1 and its recepto rs 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 E TA and ETB receptors in the cells involved in the osteogenesis of the mandi ble. Furthermore, ET-I was able to stimulate thymidine uptake and the expre ssion of the oncoprotein c-fos in the same cell types. Our results indicate that ET-I may play a putative role in epithelium-mesen chyme interaction during human craniofacial morphogenesis. Our findings are in complete accord with those of the most recent works by Yanagisawa [Yana gisawa 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 dev elopment of the pharyngeal arches.