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National Institute of Environmental Health Sciences

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Publication Detail

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

Authors: Azhar, Mohamad; Runyan, Raymond B; Gard, Connie; Sanford, L Philip; Miller, Marian L; Andringa, Anastasia; Pawlowski, Sharon; Rajan, Sudarsan; Doetschman, Thomas

Published In Dev Dyn, (2009 Feb)

Abstract: 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.

PubMed ID: 19161227 Exiting the NIEHS site

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

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