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Epicardial retinoid X receptor alpha is required for myocardial growth and coronary artery formation.

Vitamin A signals play critical roles during embryonic development. In particular, heart morphogenesis depends on vitamin A signals mediated by the retinoid X receptor alpha (RXRalpha), as the systemic mutation of this receptor results in thinning of the myocardium and embryonic lethality. However, the molecular and cellular mechanisms controlled by RXRalpha signaling in this process are unclear, because a myocardium-restricted RXRalpha mutation does not perturb heart morphogenesis. Here, we analyze a series of tissue-restricted mutations of the RXRalpha gene in the cardiac neural crest, endothelial, and epicardial lineages, and we show that RXRalpha signaling in the epicardium is required for proper cardiac morphogenesis. Moreover, we detect an additional phenotype of defective coronary arteriogenesis associated with RXRalpha deficiency and identify a retinoid-dependent Wnt signaling pathway that cooperates in epicardial epithelial-to-mesenchymal transformation.

Pubmed ID: 16352730


  • Merki E
  • Zamora M
  • Raya A
  • Kawakami Y
  • Wang J
  • Zhang X
  • Burch J
  • Kubalak SW
  • Kaliman P
  • Izpisua Belmonte JC
  • Chien KR
  • Ruiz-Lozano P


Proceedings of the National Academy of Sciences of the United States of America

Publication Data

December 20, 2005

Associated Grants

  • Agency: NHLBI NIH HHS, Id: R01 HL063714
  • Agency: NHLBI NIH HHS, Id: R01 HL063714-04

Mesh Terms

  • Animals
  • Cell Lineage
  • Chick Embryo
  • Coronary Vessels
  • Endothelial Cells
  • Fibroblast Growth Factors
  • Gene Expression Regulation, Developmental
  • Heart
  • Mice
  • Mice, Transgenic
  • Myocardium
  • Neural Crest
  • Retinoid X Receptor alpha
  • Signal Transduction
  • Wnt Proteins