Journal
JOURNAL OF CELL BIOLOGY
Volume 166, Issue 3, Pages 359-367Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200403050
Keywords
heart cushion formation; beta-catenin; endothelial cells; Wnt-signaling; transforming growth factor beta
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Funding
- Telethon [E.1254] Funding Source: Medline
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During heart development endocardial cells within the atrio-ventricular (AV) region undergo TGFP-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 TGFP induction of endocardial EMT is strongly inhibited in mice deficient for endothelial beta-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 beta-catenin/TCF/Lef transcriptional activity. In cultured endothelial cells, TGFbeta2 induces alpha-smooth muscle actin (alphaSMA) expression. This process was strongly reduced in p-catenin null cells, although TGFbeta2 induced smad phosphorylation was unchanged. These data demonstrate an involvement of beta-catenin/TCF/Lef transcriptional activity in heart cushion formation, and suggest an interaction between TGFbeta and Wnt-signaling pathways in the induction of endothelial-mesenchymal transformation.
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