Ligand-Specific Function of Transforming Growth Factor Beta in Epithelial-Mesenchymal Transition in Heart Development

The ligand specificity of transforming growth factor beta (TGF beta) in vivo in mouse cardiac cushion epithelial-to-mesenchymal transition (EMT) is poorly understood. To elucidate the function of TGF beta in cushion EMT, we analyzed Tgfb1(-/-), Tgtb2(-/-), and Tgfb3(-/-) mice between embryonic day (E) 9.5 and E14.5 using both in vitro and in vivo approaches. Atrioventricular (AV) canal collagen gel assays at E9.5 indicated normal EMT in both Tgfb1(-/-) and Tgfb3(-/-) mice. However, analysis of Tgfb2(-/-) AV explants at E9.5 and E10.5 indicated that EMT, but not cushion cell proliferation, was initially delayed but later remained persistent. This was concordant with the observation that Tgtb2(-/-) embryos, and not Tgfb1(-/-) or Tgth3(-/-) embryos, develop enlarged cushions at E14.5 with elevated levels of well-validated indicators of EMT. Collectively, these data indicate that TGF beta 2, and not TGF beta 1 or TGF beta 3, mediates cardiac cushion EMT by promoting both the initiation and cessation of EMT. Developmental Dynamics 238:431-442, 2009. (c) 2009 Wiley-Liss, Inc.