Ligand-specific function of transforming growth factor beta in epithelial-mesenchymal transition in heart development

The ligand specificity of transforming growth factor beta (TGFβ) in vivo in mouse cardiac cushion epithelial-to-mesenchymal transition (EMT) is poorly understood. To elucidate the function of TGFβ in cushion EMT, we analyzed Tgfb1^-/-, Tgfb2^-/-, 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 Tgfb2 ^-/- embryos, and not Tgfb1^-/- or Tgfb3^-/- embryos, develop enlarged cushions at E14.5 with elevated levels of well-validated indicators of EMT. Collectively, these data indicate that TGFβ2, and not TGFβ1 or TGFβ3, mediates cardiac cushion EMT by promoting both the initiation and cessation of EMT.