FOG-2, a cofactor for GATA transcription factors, is essential for heart morphogenesis and development of coronary vessels from epicardium |
| |
Authors: | Tevosian S G Deconinck A E Tanaka M Schinke M Litovsky S H Izumo S Fujiwara Y Orkin S H |
| |
Affiliation: | Division of Hematology-Oncology, Children's Hospital and Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA. |
| |
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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|