ANTIBODIES TO THE TYPE-II TGF-BETA RECEPTOR BLOCK CELL ACTIVATION ANDMIGRATION DURING ATRIOVENTRICULAR CUSHION TRANSFORMATION IN THE HEART

Epithelial-mesenchymal transformation is a critical event in the devel opment of many organ systems including the heart. Descriptive studies have implicated a number of factors in mediating this transformation, including transforming growth factor beta (TGF beta). We now report th at disruption of a TGF beta signal transduction complex by antibodies directed against the Type II TGF beta receptor blocks both the endocar dial cell activation and subsequent migration that constitute transfor mation in the chick atrioventricular (AV) cushion. The Type ZI recepto r was localized to both endothelial and endocardial cells of the chick embryo. Incubation of AV cushion explants from Stage 14, 16, and 18 e mbryos with antibody resulted in a blockade of AV endocardial cell tra nsformation by greater than 50% as measured by mesenchyme formation. S imilarly, the appearance of procollagen Type I, a marker of endocardia l cell transformation, was blocked. In addition, within 2 hr after the incubation of activated Stage 18 explants with Type 11 antibody the r ate of migration of transformed tells was decreased by 50%. These data suggest that TGF beta acts directly on AV cushion endocardial cells t o stimulate epithelial-mesenchymal transformation and that TGF beta me diates at least two distinct components of AV cushion transformation, activation and migration. (C) 1996 Academic Press, Inc.