Cloning and characterization of developmental endothelial locus-1: An embryonic endothelial cell protein that binds the αvβ3 integrin receptor
- Chiaki Hidai1,
- Thomas Zupancic2,
- Kalyani Penta3,8,
- Adel Mikhail2,
- Masatoshi Kawana1,
- Elena E. Quertermous3,
- Yoshikazu Aoka1,3,8,
- Masafumi Fukagawa4,
- Yasuhisa Matsui5,
- Doros Platika2,
- Robert Auerbach6,
- Brigid L.M. Hogan7,
- Ralph Snodgrass2, and
- Thomas Quertermous3,8,9
- Departments of 3Medicine, 4Molecular Physiology and Biophysics, and 7Cell Biology and the Howard Hughes Medical Institute, Vanderbilt University Medical School, Nashville, Tennessee 37232 USA; 1Tokyo Women’s Medical College, Tokyo 162, Japan; 2Progenitor, Inc., Menlo Park, California 94025 USA; Third Department of Internal Medicine, University of Tokyo, Tokyo, Japan; 5Department of Cell Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan; 6Department of Zoology, University of Wisconsin, Madison, Wisconsin 53202 USA
Abstract
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 αvβ3 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 αvβ3 integrin receptor and may function to regulate vascular morphogenesis or remodeling in embryonic development.
