A role for planar cell polarity signaling in angiogenesis.
The planar cell polarity (PCP) pathway is a highly conserved signaling cascade that coordinates both epithelial and axonal morphogenic movements during development. Angiogenesis also involves the growth and migration of polarized cells, although the mechanisms underlying their intercellular communication are poorly understood. Here, using cell culture assays, we demonstrate that inhibition of PCP signaling disrupts endothelial cell growth, polarity, and migration, all of which can be rescued through downstream activation of this pathway by expression of either Daam-1, Diversin or Inversin. Silencing of either Dvl2 or Prickle suppressed endothelial cell proliferation. Moreover, loss of p53 rescues endothelial cell growth arrest but not the migration inhibition caused by PCP disruption. In addition, we show that the zebrafish Wnt5 mutant (pipetail (ppt)), which has impaired PCP signaling, displays vascular developmental defects. These findings reveal a potential role for PCP signaling in the coordinated assembly of endothelial cells into vascular structures and have important implications for vascular remodeling in development and disease.
Cirone
Pasquale
P
Department of Molecular, Cellular and Developmental Biology, Yale University, Kline Biology Tower, P.O. Box 208103, New Haven, CT 06520-8103, USA.
Lin
Shengda
S
Griesbach
Hilary L
HL
Zhang
Yi
Y
Slusarski
Diane C
DC
Crews
Craig M
CM
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000818:Animals; D001808:Blood Vessels / Q000002:abnormalities / Q000187:drug effects; D051242:Caveolin 1 / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D016764:Cell Polarity / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003510:Cyclohexanes / Q000494:pharmacology; D000072261:Dishevelled Proteins; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D051379:Mice; D023421:Models, Animal; D009154:Mutation / Q000235:genetics; D018919:Neovascularization, Physiologic / Q000187:drug effects; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D010750:Phosphoproteins / Q000235:genetics; D012717:Sesquiterpenes / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism; D015027:Zebrafish; D051176:beta Catenin / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D051242:Caveolin 1; D003510:Cyclohexanes; C000606581:DVL2 protein, human; D000072261:Dishevelled Proteins; C000606582:Dvl2 protein, mouse; D010750:Phosphoproteins; D012717:Sesquiterpenes; D016159:Tumor Suppressor Protein p53; D051153:Wnt Proteins; D051176:beta Catenin; D000077609:O-(Chloroacetylcarbamoyl)fumagillol
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