RRC ID 6016
Author Phillips HM, Hildreth V, Peat JD, Murdoch JN, Kobayashi K, Chaudhry B, Henderson DJ.
Title Non-cell-autonomous roles for the planar cell polarity gene Vangl2 in development of the coronary circulation.
Journal Circ Res
Abstract 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.
Volume 102(5)
Pages 615-23
Published 2008-3-14
DOI 10.1161/CIRCRESAHA.107.160861
PMID 18174466
MeSH Animals Cell Differentiation / genetics Cell Movement / genetics Cell Polarity / genetics* Cells, Cultured Coronary Circulation / genetics* Coronary Vessel Anomalies / genetics* Coronary Vessel Anomalies / pathology Coronary Vessels / embryology* Coronary Vessels / metabolism Cytoskeleton / genetics Cytoskeleton / ultrastructure Embryo, Mammalian Fibronectins / metabolism Heart / embryology* Mice Mice, Transgenic Muscle, Smooth, Vascular / metabolism Myocardium / metabolism Myocardium / pathology Nerve Tissue Proteins / biosynthesis Nerve Tissue Proteins / physiology* Pericardium / embryology Pericardium / metabolism Stem Cells / metabolism rho-Associated Kinases / metabolism
IF 14.467
Times Cited 34
Mice RBRC01294