Essential role for Galpha13 in endothelial cells during embryonic development.
Toward identifying the roles of protease-activated receptor-1 (PAR1) and other G protein-coupled receptors important for vascular development, we investigated the role of Galpha13 in endothelial cells in the mouse embryo. LacZ inserted into Galpha13 exon 1 was highly expressed in endothelial cells at midgestation. Endothelial-specific Galpha13 knockout embryos died at embryonic days 9.5-11.5 and resembled the PAR1 knockout. Restoration of Galpha13 expression in endothelial cells by use of a Tie2 promoter-driven Galpha13 transgene rescued development of endothelial-specific Galpha13 knockout embryos as well the embryonic day 9.5 vascular phenotype in Galpha13 conventional knockouts; transgene-positive Galpha13-/- embryos developed for several days beyond their transgene-negative Galpha13-/- littermates and then manifested a previously uncharacterized phenotype that included intracranial bleeding and exencephaly. Taken together, our results suggest a critical role for Galpha13 in endothelial cells during vascular development, place Galpha13 as a candidate mediator of PAR1 signaling in this process, and reveal roles for Galpha13 in other cell types in the mammalian embryo.
Ruppel
Kathleen M
KM
Cardiovascular Research Institute and Departments of Pediatrics, Medicine, and Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143, USA.
Willison
David
D
Kataoka
Hiroshi
H
Wang
Alice
A
Zheng
Yao-Wu
YW
Cornelissen
Ivo
I
Yin
Liya
L
Xu
Shan Mei
SM
Coughlin
Shaun R
SR
D000483:Alleles; D000818:Animals; D003094:Collagen; D004338:Drug Combinations; D004622:Embryo, Mammalian / Q000166:cytology* / Q000378:metabolism*; D047108:Embryonic Development; D042783:Endothelial Cells / Q000378:metabolism*; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020043:Genes, Essential / Q000235:genetics; D007797:Laminin; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D011509:Proteoglycans; D044463:Receptor, PAR-1 / Q000378:metabolism; D015398:Signal Transduction
D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; D044463:Receptor, PAR-1; C059485:matrigel; D003094:Collagen; D044365:GTP-Binding Protein alpha Subunits, G12-G13