Hippo Signaling Mediators Yap and Taz Are Required in the Epicardium for Coronary Vasculature Development

Anamika Singh, Sindhu Ramesh, Dasan Mary Cibi, Lim Sze Yun, Jun Li, Li Li, Lauren J. Manderfield, Eric N. Olson, Jonathan A. Epstein, Manvendra K. Singh

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Formation of the coronary vasculature is a complex and precisely coordinated morphogenetic process that begins with the formation of epicardium. The epicardium gives rise to many components of the coronary vasculature, including fibroblasts, smooth muscle cells, and endothelium. Hippo signaling components have been implicated in cardiac development and regeneration. However, a role of Hippo signaling in the epicardium has not been explored. Employing a combination of genetic and pharmacological approaches, we demonstrate that inhibition of Hippo signaling mediators Yap and Taz leads to impaired epicardial epithelial-to-mesenchymal transition (EMT) and a reduction in epicardial cell proliferation and differentiation into coronary endothelial cells. We provide evidence that Yap and Taz control epicardial cell behavior, in part by regulating Tbx18 and Wt1 expression. Our findings show a role for Hippo signaling in epicardial cell proliferation, EMT, and cell fate specification during cardiac organogenesis. Singh et al. show that Hippo signaling components are expressed in proepicardial and epicardial cells and are required for coronary vasculature development. Yap and Taz regulate epicardial cell proliferation, EMT, and cell fate specification, in part by regulating Tbx18 and Wt1 expression.

Original languageEnglish (US)
Pages (from-to)1384-1393
Number of pages10
JournalCell Reports
Volume15
Issue number7
DOIs
StatePublished - May 17 2016

Keywords

  • Epicardium
  • Epithelial to mesenchymal transition (EMT)
  • Hippo signaling
  • Proepicardium
  • Taz
  • Yap

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Singh, A., Ramesh, S., Cibi, D. M., Yun, L. S., Li, J., Li, L., Manderfield, L. J., Olson, E. N., Epstein, J. A., & Singh, M. K. (2016). Hippo Signaling Mediators Yap and Taz Are Required in the Epicardium for Coronary Vasculature Development. Cell Reports, 15(7), 1384-1393. https://doi.org/10.1016/j.celrep.2016.04.027