Adgrg6/Gpr126 is required for compact wall integrity and establishing trabecular identity during cardiac trabeculation

Srivastava S, Gunawan F, Vergarajauregui S, Gentile A, Angeloni M, Petersen SC, Günther S, Ferrazzi F, Stainier DY, Engel F (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Nature Communications Nature Publishing Group: Nature Communications

Book Volume: 17

Article Number: 1484

Journal Issue: 1

DOI: 10.1038/s41467-026-69292-5

Abstract

How adhesion G protein-coupled receptors (aGPCRs) control development remains unclear. aGPCR Adgrg6/Gpr126 has been associated with heart trabeculation. Defects in this process cause cardiomyopathies and cardiac dysfunction. How cardiomyocytes attain trabecular identity is poorly understood. Here, we show that different domains of Gpr126 distinctly regulate compact wall integrity and trabecular identity. Maternal zygotic (MZ) gpr126^stl47 early truncation mutants exhibit hypotrabeculation, whereby N-cadherin distributes randomly along apical/basal/lateral membranes of compact layer cardiomyocytes. In contrast, zygotic and MZ gpr126^st49 mutants, expressing a N-terminal fragment lacking the GPS motif (NTF^ΔGPS), exhibit a multilayered ventricular wall containing polarized cardiomyocytes with normal N-cadherin localization and increased Notch activity. Notably, endocardially expressed gpr126 C-terminal fragment (CTF) reinstates trabeculation in gpr126^st49 mutants. Collectively, our data reveal domain-specific roles of Gpr126 during trabeculation, whereby the NTF is required for maintaining cell-cell adhesion and compact wall integrity, whereas the CTF is essential to provide trabecular identity.

Authors with CRIS profile

Silvia Vergarajauregui Letamendia Department of Nephropathology Miriam Angeloni Institute of Pathology Fulvia Ferrazzi Institute of Human Genetics Felix Engel Department of Nephropathology

Involved external institutions

Max Planck Institute for Heart and Lung Research / Max-Planck-Institut für Herz- und Lungenforschung

Germany (DE) Washington University in St. Louis

United States (USA) (US)

How to cite

APA:

Srivastava, S., Gunawan, F., Vergarajauregui, S., Gentile, A., Angeloni, M., Petersen, S.C.,... Engel, F. (2026). Adgrg6/Gpr126 is required for compact wall integrity and establishing trabecular identity during cardiac trabeculation. Nature Communications, 17(1). https://doi.org/10.1038/s41467-026-69292-5

MLA:

Srivastava, Swati, et al. "Adgrg6/Gpr126 is required for compact wall integrity and establishing trabecular identity during cardiac trabeculation." Nature Communications 17.1 (2026).

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