title: TAp63 is important for cardiac differentiation of embryonic stem cells and heart development.
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.
authors: INSERM U898, Nice, France.
authors: Matthieu
authors: M
authors: Rouleau
authors: Alain
authors: A
authors: Medawar
authors: Laurent
authors: L
authors: Hamon
authors: Shoham
authors: S
authors: Shivtiel
authors: Zohar
authors: Z
authors: Wolchinsky
authors: Huiqing
authors: H
authors: Zhou
authors: Laura
authors: L
authors: De Rosa
authors: Eleonora
authors: E
authors: Candi
authors: Stéphanie
authors: S
authors: de la Forest Divonne
authors: Marja L
authors: ML
authors: Mikkola
authors: Hans
authors: H
authors: van Bokhoven
authors: Caterina
authors: C
authors: Missero
authors: Gerry
authors: G
authors: Melino
authors: Michel
authors: M
authors: Pucéat
authors: Daniel
authors: D
authors: Aberdam
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism* / Q000648:ultrastructure; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D050993:GATA6 Transcription Factor / Q000235:genetics / Q000378:metabolism; D024002:HMGB Proteins / Q000235:genetics / Q000378:metabolism; D006321:Heart / Q000196:embryology* / Q000254:growth & development; D015151:Immunoblotting; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055760:SOXF Transcription Factors / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
chemical_list: D050993:GATA6 Transcription Factor; D024002:HMGB Proteins; D010750:Phosphoproteins; D055760:SOXF Transcription Factors; C511606:Sox17 protein, mouse; D015534:Trans-Activators; C486419:Trp63 protein, mouse