| RRC ID |
6016
|
| 著者 |
Phillips HM, Hildreth V, Peat JD, Murdoch JN, Kobayashi K, Chaudhry B, Henderson DJ.
|
| タイトル |
Non-cell-autonomous roles for the planar cell polarity gene Vangl2 in development of the coronary circulation.
|
| ジャーナル |
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.
|
| 巻・号 |
102(5)
|
| ページ |
615-23
|
| 公開日 |
2008-3-14
|
| DOI |
10.1161/CIRCRESAHA.107.160861
|
| PII |
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
|
| 引用数 |
34
|
|
WOS 分野
|
CARDIAC & CARDIOVASCULAR SYSTEMS
HEMATOLOGY
PERIPHERAL VASCULAR DISEASE
|
| リソース情報 |
| 実験動物マウス |
RBRC01294 |
