RESEARCH PAPER
Cloning and characterization of developmental endothelial locus-1: An embryonic endothelial cell protein that binds the v3 integrin receptor

Departments of ³ Medicine, ⁴ Molecular Physiology and Biophysics, and ⁷ Cell Biology and the Howard Hughes Medical Institute, Vanderbilt University Medical School, Nashville, Tennessee 37232 USA; ¹ Tokyo Women's Medical College, Tokyo 162, Japan; ² Progenitor, Inc., Menlo Park, California 94025 USA; ⁴ Third Department of Internal Medicine, University of Tokyo, Tokyo, Japan; ⁵ Department of Cell Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan; ⁶ Department of Zoology, University of Wisconsin, Madison, Wisconsin 53202 USA

We have taken advantage of an enhancer trap event in a line of transgenic mice to identify a unique developmentally regulated endothelial cell locus (Del1). The protein encoded in this locus contains three EGF-like repeats homologous to those in Notch and related proteins, including 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 adhesion of endothelial cells through interaction with the v3 integrin receptor. Embryonic endothelial-like yolk sac cells expressing recombinant Del1 protein, or grown on an extracellular matrix containing Del1 protein, are inhibited from forming vascular-like structures. Expression of Del1 protein in the chick chorioallantoic membrane leads to loss of vascular integrity and promotes vessel remodeling. Del1 is thus a new ligand for the v3 integrin receptor and may function to regulate vascular morphogenesis or remodeling in embryonic development.

[Key Words: Endothelial; integrin; cloning; angiogenesis; embryogenesis; vasculature]
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