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