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- Title
TAp63 Is Important for Cardiac Differentiation of Embryonic Stem Cells and Heart Development.
- Authors
Rouleau, Matthieu; Medawar, Alain; Hamon, Laurent; Shivtiel, Shoham; Wolchinsky, Zohar; Zhou, Huiqing; De Rosa, Laura; Candi, Eleonora; de la Forest Divonne, Stéphanie; Mikkola, Marja L.; van Bokhoven, Hans; Missero, Caterina; Melino, Gerry; Pucéat, Michel; Aberdam, Daniel
- 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 wild-type 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. S TEM C ELLS 2011;29:1672-1683
- Subjects
EPITHELIUM; EMBRYONIC stem cells; HEART cells; MITOCHONDRIA; SKIN physiology
- Publication
Stem Cells, 2011, Vol 29, Issue 11, p1672
- ISSN
1066-5099
- Publication type
Article
- DOI
10.1002/stem.723