title: FOG-2, a cofactor for GATA transcription factors, is essential for heart morphogenesis and development of coronary vessels from epicardium.
abstract: We disrupted the FOG-2 gene in mice to define its requirement in vivo. FOG-2(-/-) embryos die at midgestation with a cardiac defect characterized by a thin ventricular myocardium, common atrioventricular canal, and the tetralogy of Fallot malformation. Remarkably, coronary vasculature is absent in FOG-2(-/-) hearts. Despite formation of an intact epicardial layer and expression of epicardium-specific genes, markers of cardiac vessel development (ICAM-2 and FLK-1) are not detected, indicative of failure to activate their expression and/or to initiate the epithelial to mesenchymal transformation of epicardial cells. Transgenic reexpression of FOG-2 in cardiomyocytes rescues the FOG-2(-/-) vascular phenotype, demonstrating that FOG-2 function in myocardium is required and sufficient for coronary vessel development. Our findings provide the molecular inroad into the induction of coronary vasculature by myocardium in the developing heart.
authors.affiliation: Division of Hematology-Oncology, Children's Hospital and Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA.
authors.forename: S G
authors.initials: SG
authors.lastname: Tevosian
authors.forename: A E
authors.initials: AE
authors.lastname: Deconinck
authors.forename: M
authors.initials: M
authors.lastname: Tanaka
authors.forename: M
authors.initials: M
authors.lastname: Schinke
authors.forename: S H
authors.initials: SH
authors.lastname: Litovsky
authors.forename: S
authors.initials: S
authors.lastname: Izumo
authors.forename: Y
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: S H
authors.initials: SH
authors.lastname: Orkin
mesh_terms: D000818:Animals; D003331:Coronary Vessels / Q000196:embryology* / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology*; D005314:Embryonic and Fetal Development; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006321:Heart / Q000196:embryology* / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis; D010496:Pericardium / Q000196:embryology; D014157:Transcription Factors / Q000502:physiology*; D016335:Zinc Fingers
chemical_list: D004268:DNA-Binding Proteins; D014157:Transcription Factors; C492170:Zfpm2 protein, mouse