FOG-2, a cofactor for GATA transcription factors, is essential for heart morphogenesis and development of coronary vessels from epicardium

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 tetral ogy of Fallot malformation. Remarkably, coronary vasculature is absent in F OG-2(-/-) hearts. Despite formation of an intact epicardial layer and expre ssion 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 re scues the FOG-2(-/-) vascular phenotype, demonstrating that FOG-2 function in myocardium is required and sufficient for coronary vessel development. O ur findings provide the molecular inroad into the induction of coronary vas culature by myocardium in the developing heart.