G-protein-coupled receptor S1P1 acts within endothelial cells to regulate vascular maturation

Sphingosine-1-phosphate (S1P) stimulates signaling pathways via G-protein-coupled receptors and triggers diverse cellular processes, including growth, survival, and migration. In S1P(1) receptor-deficient embryos, blood vessels were incompletely covered by vascular smooth muscle cells (VSMCs), indicating the S1P(1) receptor regulates vascular maturation. Because S1P(1) receptor expression is not restricted to a particular cell type, it was not known whether the S1P(1) receptor controlled VSMC coverage of vessels in a cell-autonomous fashion by functioning directly in VSMCs or indirectly through its activity in endothelial cells (ECs). By using the Cre/IoxP system, we disrupted the S1P(1) gene solely in ECs. The phenotype of the conditional mutant embryos mimicked the one obtained in the embryos globally deficient in S1P(1). Thus, vessel coverage by VSMCs is directed by the activity of the S1P(1) receptor in ECs.