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

  1. Rebeca Torregrosa-Carrión 12
  2. Rebeca Piñeiro-Sabarís 12
  3. Marcos Siguero-Álvarez 12
  4. Joaquím Grego-Bessa 12
  5. Luis Luna-Zurita 12
  6. Vitor Samuel Fernandes 12
  7. Donal MacGrogan 12
  8. Didier Y. R. Stainier 3
  9. José Luis de la Pompa 12
  1. 1 Intercellular Signalling in Cardiovascular Development and Disease Laboratory, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
  2. 2 Ciber de Enfermedades Cardiovasculares, 28029 Madrid, Spain.
  3. 3 Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany.
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Revista:
Science Advances

ISSN: 2375-2548

Año de publicación: 2021

Volumen: 7

Número: 46

Tipo: Artículo

DOI: 10.1126/SCIADV.ABJ5445 GOOGLE SCHOLAR lock_openAcceso abierto editor

Otras publicaciones en: Science Advances

Resumen

Mutations in the G protein–coupled receptor GPR126/ADGRG6 cause human diseases, including defective peripheral nervous system (PNS) myelination. To study GPR126 function, we generated new genetic mice and zebrafish models. Murine Gpr126 is expressed in developing heart endocardium, and global Gpr126 inactivation is embryonically lethal, with mutants having thin-walled ventricles but unaffected heart patterning or maturation. Endocardial-specific Gpr126 deletion does not affect heart development or function, and transgenic endocardial GPR126 expression fails to rescue lethality in Gpr126-null mice. Zebrafish gpr126 mutants display unaffected heart development. Gpr126 is also expressed in placental trophoblast giant cells. Gpr126-null mice with a heterozygous placenta survive but exhibit GPR126-defective PNS phenotype. In contrast, Gpr126-null embryos with homozygous mutant placenta die but are rescued by placental GPR126 expression. Gpr126-deficient placentas display down-regulation of preeclampsia markers Mmp9, Cts7, and Cts8. We propose that the placenta-heart axis accounts for heart abnormalities secondary to placental defects in Gpr126 mutants.

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