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Cell Rep. 2016 May 17;15(7):1384-1393. doi: 10.1016/j.celrep.2016.04.027. Epub 2016 May 5.

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

Author information

1
Program in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School Singapore, Singapore 169857, Singapore.
2
National Heart Research Institute Singapore, National Heart Center Singapore, Singapore 169609, Singapore.
3
Department of Cell and Developmental Biology, Cardiovascular Institute and Institute for Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
4
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA.
5
Department of Cell and Developmental Biology, Cardiovascular Institute and Institute for Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: epsteinj@upenn.edu.
6
Program in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School Singapore, Singapore 169857, Singapore; National Heart Research Institute Singapore, National Heart Center Singapore, Singapore 169609, Singapore; Department of Cell and Developmental Biology, Cardiovascular Institute and Institute for Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: manvendra.singh@duke-nus.edu.sg.

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.

KEYWORDS:

Hippo signaling; Taz; Yap; epicardium; epithelial to mesenchymal transition (EMT); proepicardium

PMID:
27160901
PMCID:
PMC4871746
DOI:
10.1016/j.celrep.2016.04.027
[Indexed for MEDLINE]
Free PMC Article

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