TGFβ type III and TGFβ type II receptors have distinct activities during epithelial-mesenchymal cell transformation in the embryonic heart

During the early stages of heart development, progenitors for the heart valves and septa come from endothelial cells via a developmental process known as "epithelial-mesenchymal cell transformation." This process is restricted to the atrioventricular (AV) canal and outflow tract portions of the embryonic heart. TGF beta signal transduction pathways play critical roles during epithelial-mesenchymal cell transformation in heart development. Previously, we showed that both TGF beta Type II (T beta RII) and Type III (T beta RIII) receptors are required to mediate epithelial mesenchymal cell transformation in chick heart. Further, distinct TGF beta2 and TGF beta3 activities correspond to separate components of the embryonic cell transformation process. Studies by others of TGF beta -mediated inhibition of cell proliferation produced a model where T beta RIII functions by facilitating TGF beta2 binding to T beta RII. In the present study, we provide evidence that T beta RIII mediates distinct cellular responses from those of T beta RII. Blocking antibody for T beta RIII, but not antibody against T beta RII, specifically inhibits the endothelial cell-cell separation step. Examination of developmental markers, perturbed by blocking T beta RIII antibody, revealed a pattern of expression distinctively different from that of T beta RII antibody treatment. These data show that a distinct T beta RIII-mediated process is required for endothelial cell-cell separation during epithelial mesenchymal cell transformation. As TGF beta2 mediates endothelial cell-cell separation, the data point to a specific association of TGF beta2 and T beta RIII in the cell separation step of epithelial mesenchymal cell transformation. We conclude that distinct T beta RII and T beta RIII signal transduction pathways mediate epithelial-mesenchymal cell transformation in the heart. (C) 2001 Wiley-Liss, Inc.