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Lookup NU author(s): Dr Helen PhillipsORCiD, Dr Victoria Hildreth, Dr Jonathan Peat, Dr Bill Chaudhry, Professor Deborah HendersonORCiD
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Establishment of cellular polarity is essential for the development of many tissues. In this study, we describe defects in the formation of the coronary vasculature in the loop-tail (Lp) mutant in which the planar cell polarity (PCP) gene, Vangl2, is disrupted. Although Vangl2 is expressed exclusively in the myocardial cells of the developing heart, the coronary vessels do not develop an intact smooth muscle layer, and there are enlarged, ectopic vessels on the surface of the heart. Reduced fibronectin deposition in the subepicardial space is associated with limited migration of epicardially derived cells (EPDCs) into the ventricular myocardium and likely contributes to these defects. Analysis of cardiomyocytes shows that the actin cytoskeleton is disrupted and the cytoarchitecture of the ventricular myocardium is abnormal in Lp/Lp hearts. Moreover, activation of RhoA/Rho kinase signaling is disrupted in these cells. Conditional inhibition of myocardial Rho kinase activity disrupts the organization of the cardiomyocytes and formation of the coronary vessels to produce the same spectrum of defects as seen in Lp. These data suggest that Vangl2 and Rho kinase act cell autonomously in the myocardium to regulate the organization of cardiomyocytes but also have non-cell-autonomous effects on the formation of the coronary vasculature. © 2008 American Heart Association, Inc.
Author(s): Phillips HM, Hildreth V, Peat JD, Murdoch JN, Kobayashi K, Chaudhry B, Henderson DJ
Publication type: Article
Publication status: Published
Journal: Circulation Research
Year: 2008
Volume: 102
Issue: 5
Pages: 615-623
ISSN (print): 0009-7330
ISSN (electronic): 1524-4571
Publisher: Lippincott Williams & Wilkins
URL: http://dx.doi.org/10.1161/CIRCRESAHA.107.160861
DOI: 10.1161/CIRCRESAHA.107.160861
PubMed id: 18174466
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