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

Dev Dyn. 2009 Feb;238(2):431-42. doi: 10.1002/dvdy.21854.


The ligand specificity of transforming growth factor beta (TGFbeta) in vivo in mouse cardiac cushion epithelial-to-mesenchymal transition (EMT) is poorly understood. To elucidate the function of TGFbeta 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 TGFbeta2, and not TGFbeta1 or TGFbeta3, mediates cardiac cushion EMT by promoting both the initiation and cessation of EMT.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / physiology
  • Cell Proliferation
  • Endothelial Cells / cytology
  • Endothelial Cells / metabolism
  • Epithelial Cells / cytology
  • Epithelial Cells / physiology*
  • Heart / embryology*
  • Heart / physiology
  • Ligands
  • Mesoderm / cytology
  • Mesoderm / embryology*
  • Mesoderm / metabolism
  • Mice
  • Mice, Knockout
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / physiology*
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / physiology
  • Transforming Growth Factor beta2 / genetics
  • Transforming Growth Factor beta2 / physiology
  • Transforming Growth Factor beta3 / genetics
  • Transforming Growth Factor beta3 / physiology


  • Ligands
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Transforming Growth Factor beta2
  • Transforming Growth Factor beta3