IDENTIFICATION AND LOCALIZATION OF ENDOTHELIN-1 AND ITS RECEPTORS IN HUMAN FETAL JAWS.

In the mouse, disruption of the endothelin-1 (ET-1) gene causes severe craniofacial deformities, including mandibular hypoplasia. Since the phenotype of ET-1-deficient mice shows features in common with inherited human mandibulofacial dysostosis, we investigated the presence of ET-1 and its receptors in human fetal craniofacial tissues of 9- to 12-week-old fetuses. We found that ET-1 is immunolocalized in the epithelial cells of the oral cavity. Radioligand binding studies indicate the presence of elevated concentrations of both ETA and ETB receptors in membranes derived from fetal jaws. Using autoradiography, 125I-ET-1 binding sites were shown to be localized within the embryonic mandibular process of the oral cavity, where they were confined to the mesenchymal-derived osteogenic cells. Our data suggest a role for ET-1 in the development of the human mandible.