title: The G-protein-coupled receptor APJ is expressed in the second heart field and regulates Cerberus-Baf60c axis in embryonic stem cell cardiomyogenesis.
abstract: OBJECTIVE
  Mammalian cardiomyogenesis occurs through a multistep process that requires a complex network of tightly regulated extracellular signals, which integrate with the genetic and epigenetic machinery to maintain, expand, and regulate the differentiation of cardiac progenitor cells. Pluripotent embryonic stem cells (ESCs) recapitulate many aspects of development, and have provided an excellent opportunity to dissect the molecular mechanisms underlying cardiomyogenesis, which is still incompletely defined.
  
  
  RESULTS
  We provide new in vivo evidence that the G-protein-coupled receptor angiotensin receptor-like 1 (Apj) is expressed in the mesodermal cells of the second heart field, a population of cardiac progenitors that give rise to a major part of the definitive heart. By combining loss-and-gain of function studies in mouse ESCs, we show that Apj (i) controls the balance between proliferation and cardiovascular differentiation, (ii) regulates the Nodal/Bone Morphogenetic Protein antagonist Cerberus and the Baf60c/Smarcd3 subunit of the Brg1/Brm-associated factors (BAF) chromatin-remodelling complex.
  
  
  CONCLUSIONS
  We propose a model in which Apj controls a regulatory Cerberus-Baf60c pathway in pluripotent stem cell cardiomyogenesis, and speculate that this regulatory circuit may regulate cardiac progenitor cell behaviour.
authors.affiliation: Stem Cell Fate Laboratory, Institute of Genetics and Biophysics 'A.Buzzati-Traverso', CNR, Naples, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: D'Aniello
authors.forename: Alessandro
authors.initials: A
authors.lastname: Fiorenzano
authors.forename: Salvatore
authors.initials: S
authors.lastname: Iaconis
authors.forename: Giovanna L
authors.initials: GL
authors.lastname: Liguori
authors.forename: Gennaro
authors.initials: G
authors.lastname: Andolfi
authors.forename: Gilda
authors.initials: G
authors.lastname: Cobellis
authors.forename: Annalisa
authors.initials: A
authors.lastname: Fico
authors.forename: Gabriella
authors.initials: G
authors.lastname: Minchiotti
mesh_terms: D000818:Animals; D000075244:Apelin Receptors; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D002868:Chromosomal Proteins, Non-Histone / Q000502:physiology*; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000502:physiology; D016207:Cytokines; D053595:Embryonic Stem Cells / Q000166:cytology*; D006321:Heart / Q000196:embryology*; D051379:Mice; D009124:Muscle Proteins / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000166:cytology*; D055457:Nodal Protein / Q000037:antagonists & inhibitors*; D011506:Proteins / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D015398:Signal Transduction; D051899:Smad2 Protein / Q000502:physiology
chemical_list: D000075244:Apelin Receptors; C491285:Aplnr protein, mouse; D019485:Bone Morphogenetic Proteins; C110586:Cer1 protein, mouse; D002868:Chromosomal Proteins, Non-Histone; D050761:Cyclin-Dependent Kinase Inhibitor p57; D016207:Cytokines; D009124:Muscle Proteins; D055457:Nodal Protein; D011506:Proteins; D043562:Receptors, G-Protein-Coupled; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; C494055:Smarcd3 protein, mouse
keywords: Epigenetic; G-protein-coupled receptors; Myocardial progenitors; Second heart field; Stem cells