β-Catenin is required for endothelial-mesenchymal transformation during heart cushion development in the mouse

  • Stefan Liebner
    1FIRC Institute of Molecular Oncology, University of Milan, 20139 Milan, Italy
  • Anna Cattelino
    1FIRC Institute of Molecular Oncology, University of Milan, 20139 Milan, Italy
  • Radiosa Gallini
    1FIRC Institute of Molecular Oncology, University of Milan, 20139 Milan, Italy
  • Noemi Rudini
    1FIRC Institute of Molecular Oncology, University of Milan, 20139 Milan, Italy
  • Monica Iurlaro
    1FIRC Institute of Molecular Oncology, University of Milan, 20139 Milan, Italy
  • Stefano Piccolo
    4Department of Histology, Microbiology and Medical Biotechnologies, University of Padua, 35100 Padua, Italy
  • Elisabetta Dejana
    1FIRC Institute of Molecular Oncology, University of Milan, 20139 Milan, Italy

書誌事項

公開日
2004-08-02
DOI
  • 10.1083/jcb.200403050
公開者
Rockefeller University Press

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説明

<jats:p>During heart development endocardial cells within the atrio-ventricular (AV) region undergo TGFβ-dependent epithelial-mesenchymal transformation (EMT) and invade the underlying cardiac jelly. This process gives rise to the endocardial cushions from which AV valves and part of the septum originate. In this paper we show that in mouse embryos and in AV explants TGFβ induction of endocardial EMT is strongly inhibited in mice deficient for endothelial β-catenin, leading to a lack of heart cushion formation. Using a Wnt-signaling reporter mouse strain, we demonstrated in vivo and ex vivo that EMT in heart cushion is accompanied by activation of β-catenin/TCF/Lef transcriptional activity. In cultured endothelial cells, TGFβ2 induces α-smooth muscle actin (αSMA) expression. This process was strongly reduced in β-catenin null cells, although TGFβ2 induced smad phosphorylation was unchanged. These data demonstrate an involvement of β-catenin/TCF/Lef transcriptional activity in heart cushion formation, and suggest an interaction between TGFβ and Wnt-signaling pathways in the induction of endothelial-mesenchymal transformation.</jats:p>

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