TAp63 is important for cardiac differentiation of embryonic stem cells and heart development

Matthieu Rouleau, Alain Medawar, Laurent Hamon, Shoham Shivtiel, Zohar Wolchinsky, Huiqing Zhou, Laura De Rosa, Eleonora Candi, Stéphanie De La Forest Divonne, Marja L. Mikkola, Hans Van Bokhoven, Caterina Missero, Gerry Melino, Michel Pucéat, Daniel Aberdam

Research output: Contribution to journalArticlepeer-review

Abstract

p63, a member of the p53 family, is essential for skin morphogenesis and epithelial stem cell maintenance. Here, we report an unexpected role of TAp63 in cardiogenesis. p63 null mice exhibit severe defects in embryonic cardiac development, including dilation of both ventricles, a defect in trabeculation and abnormal septation. This was accompanied by myofibrillar disarray, mitochondrial disorganization, and reduction in spontaneous calcium spikes. By the use of embryonic stem cells (ESCs), we show that TAp63 deficiency prevents expression of pivotal cardiac genes and production of cardiomyocytes. TAp63 is expressed by endodermal cells. Coculture of p63-knockdown ESCs with wildtype ESCs, supplementation with Activin A, or overexpression of GATA-6 rescue cardiogenesis. Therefore, TAp63 acts in a non-cell-autonomous manner by modulating expression of endodermal factors. Our findings uncover a critical role for p63 in cardiogenesis that could be related to human heart disease.

Original languageEnglish
Pages (from-to)1672-1683
Number of pages12
JournalStem Cells
Volume29
Issue number11
DOIs
Publication statusPublished - Nov 2011

Keywords

  • Cardiogenesis
  • Cardiomyopathy
  • GATA
  • p63
  • sox17
  • trp63

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Medicine

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