Antibodies to the type II TGFβ receptor block cell activation and migration during atrioventricular cushion transformation in the heart

Abstract

Epithelial-mesenchymal transformation is a critical event in the development of many organ systems including the heart. Descriptive studies have implicated a number of factors in mediating this transformation, including transforming growth factor β (TGFβ). We now report that disruption of a TGFβ signal transduction complex by antibodies directed against the Type II TGFβ receptor blocks both the endocardial cell activation and subsequent migration that constitute transformation in the chick atrioventricular (AV) cushion. The Type II receptor was localized to both endothelial and endocardial cells of the chick embryo. Incubation of AV cushion explants from Stage 14, 16, and 18 embryos with antibody resulted in a blockade of AV endocardial cell transformation by greater than 50% as measured by mesenchyme formation. Similarly, the appearance of procollagen Type I, a marker of endocardial cell transformation, was blocked. In addition, within 2 hr after the incubation of activated Stage 18 explants with Type II antibody the rate of migration of transformed cells was decreased by 50%. These data suggest that TGFβ acts directly on AV cushion endocardial cells to stimulate epithelial mesenchymal transformation and that TGFβ mediates at least two distinct components of AV cushion transformation, activation and migration.