Adhesion G protein-coupled receptor Gpr126/Adgrg6 is essential for placental development.

Mutations in the G protein–coupled receptor cause human diseases, including defective peripheral nervous system (PNS) myelination. To study GPR126 function, we generated new genetic mice and zebrafish models. Murine is expressed in developing heart endocardium, and global inactivation is embryonically lethal, with mutants having thin-walled ventricles but unaffected heart patterning or maturation. Endocardial-specific deletion does not affect heart development or function, and transgenic endocardial expression fails to rescue lethality in -null mice. Zebrafish mutants display unaffected heart development. is also expressed in placental trophoblast giant cells. -null mice with a heterozygous placenta survive but exhibit GPR126-defective PNS phenotype. In contrast, -null embryos with homozygous mutant placenta die but are rescued by placental expression. -deficient placentas display down-regulation of preeclampsia markers , , and . We propose that the placenta-heart axis accounts for heart abnormalities secondary to placental defects in mutants.