title: BMP and FGF regulate the differentiation of multipotential pericardial mesoderm into the myocardial or epicardial lineage.
abstract: Proepicardial cells give rise to epicardium, coronary vasculature and cardiac fibroblasts. The proepicardium is derived from the mesodermal lining of the prospective pericardial cavity that simultaneously contributes myocardium to the venous pole of the elongating primitive heart tube. Using proepicardial explant cultures, we show that proepicardial cells have the potential to differentiate into cardiac muscle cells, reflecting the multipotency of this pericardial mesoderm. The differentiation into the myocardial or epicardial lineage is mediated by the cooperative action of BMP and FGF signaling. BMP2 is expressed in the distal IFT myocardium and stimulates cardiomyocyte formation. FGF2 is expressed in the proepicardium and stimulates differentiation into the epicardial lineage. In the base of the proepicardium, coexpression of BMP2 and FGF2 inhibits both myocardial and epicardial differentiation. We conclude that the epicardial/myocardial lineage decisions are mediated by an extrinsic, inductive mechanism, which is determined by the position of the cells in the pericardial mesoderm.
authors.affiliation: Experimental and Molecular Cardiology Group, Academic Medical Center, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Boudewijn P T
authors.initials: BP
authors.lastname: Kruithof
authors.forename: Bram
authors.initials: B
authors.lastname: van Wijk
authors.forename: Semir
authors.initials: S
authors.lastname: Somi
authors.forename: Marianna
authors.initials: M
authors.lastname: Kruithof-de Julio
authors.forename: José María
authors.initials: JM
authors.lastname: Pérez Pomares
authors.forename: Frank
authors.initials: F
authors.lastname: Weesie
authors.forename: Andy
authors.initials: A
authors.lastname: Wessels
authors.forename: Antoon F M
authors.initials: AF
authors.lastname: Moorman
authors.forename: Maurice J B
authors.initials: MJ
authors.lastname: van den Hoff
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D002642:Chick Embryo; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D008648:Mesoderm / Q000166:cytology*; D039902:Multipotent Stem Cells / Q000166:cytology*; D009206:Myocardium / Q000166:cytology*; D032383:Myocytes, Cardiac / Q000166:cytology; D010496:Pericardium / Q000166:cytology; D016212:Transforming Growth Factor beta / Q000502:physiology*
chemical_list: D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2