TGFβ-mediated RhoA expression is necessary for epithelial-mesenchymal transition in the embryonic chick heart

André Luiz P. Tavares, Melania E. Mercado-Pimentel, Raymond B. Runyan, Gregory T. Kitten

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

Endothelia in the atrioventricular canal (AVC) of the embryonic heart undergo an epithelial-mesenchymal transition (EMT) and migrate into the underlying extracellular matrix. We explore here whether RhoA mediates this EMT. RhoA was detected in all cells of the chick heart during the stages studied. Expression was elevated when EMT was actively occurring. Explants treated with C3 exoenzyme in collagen gel cultures showed a significant decrease in mesenchymal cell numbers. siRNA was used to inhibit RhoA mRNA, and both activated endothelial and mesenchymal cells decreased significantly with treatment. Loss of RhoA produced a reduction of RhoB, cyclin-b2, and β-catenin messages showing that these genes are regulated downstream of RhoA. In contrast, runx-2 was not reduced. Inhibition of TGFβ3 or TGFβ2 activity caused a large reduction of RhoA message. These data place RhoA in TGFβ regulated pathways for both endothelial activation and mesenchymal invasion and demonstrate a functional requirement during EMT.

Original languageEnglish (US)
Pages (from-to)1589-1598
Number of pages10
JournalDevelopmental Dynamics
Volume235
Issue number6
DOIs
StatePublished - Jun 2006

Keywords

  • Cardiac development
  • Cardiac valve
  • Cushion formation
  • EMT
  • Rho-GTPases
  • Valvuloseptal development

ASJC Scopus subject areas

  • Developmental Biology

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