The g protein-coupled receptor agtrl1b regulates early development of myocardial progenitors.
While many factors that modulate the morphogenesis and patterning of the embryonic heart have been identified, relatively little is known about the molecular events that regulate the differentiation of progenitor cells fated to form the myocardium. Here, we show that zebrafish grinch (grn) mutants form a reduced number of myocardial progenitor cells, which results in a profound deficit in cardiomyocyte numbers in the most severe cases. We show that grn encodes the G protein-coupled receptor (GPCR) Agtrl1b, a known regulator of adult cardiovascular physiology. Ectopic expression of Apelin, an Agtrl1b ligand, results in the complete absence of cardiomyocytes. Data from transplantation and transgenic approaches indicate that Agtrl1 signaling plays a cell-autonomous role in myocardial specification, with activity being required coincident with the onset of gastrulation movements. These results support a model in which agtrl1b regulates the migration of cells fated to form myocardial progenitors.
Scott
Ian C
IC
Department of Biochemistry and Biophysics, Programs in Developmental Biology, Genetics and Human Genetics, and Cardiovascular Research Institute, University of California, San Francisco, 1550 4th Street, San Francisco, CA 94158, USA. ian.scott@sickkids.ca
Masri
Bernard
B
D'Amico
Leonard A
LA
Jin
Suk-Won
SW
Jungblut
Benno
B
Wehman
Ann M
AM
Baier
Herwig
H
Audigier
Yves
Y
Stainier
Didier Y R
DY
D000818:Animals; D030801:Animals, Genetically Modified / Q000196:embryology / Q000235:genetics; D000075244:Apelin Receptors; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D005775:Gastrula / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006321:Heart / Q000196:embryology*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D032386:Myoblasts, Cardiac / Q000166:cytology / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D038081:Organogenesis / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000502:physiology*
C513482:APLN protein, Xenopus; C105530:APLNR protein, Xenopus; D000075244:Apelin Receptors; D036341:Intercellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; C519093:apelin receptor, zebrafish