Grant: Operating Grant

A clear understanding of congenital heart disease requires knowledge of the origins and interconnections between all of the cell types that contribute to the heart and support its formation during fetal development. The cells that form the heart communicate through molecules known as receptors that receive and interpret biochemical messages. We have characterized the receptor Endoglin which is found on endothelial cells: the inner lining of all blood vessels and the heart. Our previous studies showed that Endoglin is required for formation of cellular structures known as endocardial cushions that partition the early embryonic heart tube into chambers, and which become the valves that regulate blood flow in the pumping heart. In this application we propose to determine the biochemical pathway used by Endoglin in the heart, and the effects Endoglin has on cellular processes such as migration or cell division in this context. We will accomplish this by engineering genetic changes in mice such that Endoglin can be inactivated in a cell type, and time dependent manner. Our studies will advance our understanding of the process of valve formation in normal and abnormal heart development.