Essential role for Gα13 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 G alpha(13) in endothelial cells in the mouse embryo. LacZ inserted into G alpha(13) exon 1 was highly expressed in endothelial cells at midgestation. Endothelial-specific G alpha(13) knockout embryos died at embryonic days 9.5-11.5 and resembled the PAR1 knockout. Restoration of G alpha(13) expression in endothelial cells by use of a Tie2 promoter-driven G alpha(13) transgene rescued development of endothelial-specific G alpha(13) knockout embryos as well the embryonic day 9.5 vascular phenotype in G alpha(13) conventional knockouts; transgene-positive G alpha(-/-)(13) embryos developed for several days beyond their transgene-negative G alpha(-/-)(13) littermates and then manifested a previously uncharacterized phenotype that included intracranial bleeding and exencephaly. Taken together, our results suggest a critical role for G alpha(13) in endothelial cells during vascular development, place G alpha(13) as a candidate mediator of PAR1 signaling in this process, and reveal roles for G alpha(13) in other cell types in the mammalian embryo.