CLONING AND CHARACTERIZATION OF DEVELOPMENTAL ENDOTHELIAL LOCUS-1 - AN EMBRYONIC ENDOTHELIAL-CELL PROTEIN THAT BINDS THE ALPHA-V-BETA-3 INTEGRIN RECEPTOR

We have taken advantage of an enhancer trap event in a line of transge nic mice to identify a unique developmentally regulated endothelial ce ll locus (Del1). The protein encoded in this locus contains three EGF- like repeats homologous to those in Notch and related proteins, includ ing an EGF-like repeat that contains an RGD motif, and two discoidin I -like domains. Del1 is shown to be a matrix protein and to promote adh esion of endothelial cells through interaction with the alpha v beta 3 integrin receptor. Embryonic endothelial-like yolk sac cells expressi ng recombinant Del1 protein, or grown on an extracellular matrix conta ining Del1 protein, are inhibited from forming vascular-like structure s. Expression of Del1 protein in the chick chorioallantoic membrane le ads to loss of vascular integrity and promotes vessel remodeling. Del1 is thus a new ligand for the alpha v beta 3 integrin receptor and may function to regulate vascular morphogenesis or remodeling in embryoni c development.