Adhesion G protein-coupled receptor Gpr126/Adgrg6 is essential for placental development.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34767447.
- Also identified by DOI 10.1126/sciadv.abj5445 and PMC identifier 8589310.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Mutations in the G protein–coupled receptor <i>GPR126/ADGRG6</i> cause human diseases, including defective peripheral nervous system (PNS) myelination. To study GPR126 function, we generated new genetic mice and zebrafish models. Murine <i>Gpr126</i> is expressed in developing heart endocardium, and global <i>Gpr126</i> inactivation is embryonically lethal, with mutants having thin-walled ventricles but unaffected heart patterning or maturation. Endocardial-specific <i>Gpr126</i> deletion does not affect heart development or function, and transgenic endocardial <i>GPR126</i> expression fails to rescue lethality in <i>Gpr126</i>-null mice. Zebrafish <i>gpr126</i> mutants display unaffected heart development. <i>Gpr126</i> is also expressed in placental trophoblast giant cells. <i>Gpr126</i>-null mice with a heterozygous placenta survive but exhibit GPR126-defective PNS phenotype. In contrast, <i>Gpr126</i>-null embryos with homozygous mutant placenta die but are rescued by placental <i>GPR126</i> expression. <i>Gpr126</i>-deficient placentas display down-regulation of preeclampsia markers <i>Mmp9</i>, <i>Cts7</i>, and <i>Cts8</i>. We propose that the placenta-heart axis accounts for heart abnormalities secondary to placental defects in <i>Gpr126</i> mutants.