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A role for planar cell polarity signaling in angiogenesis
Journal article   Peer reviewed

A role for planar cell polarity signaling in angiogenesis

Pasquale Cirone, Shengda Lin, Hilary L Griesbach, Yi Zhang, Diane C Slusarski and Craig M Crews
Angiogenesis (London), Vol.11(4), pp.347-360
2008
DOI: 10.1007/s10456-008-9116-2
PMCID: PMC3547076
PMID: 18798004

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Abstract

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.
Neovascularization, Physiologic - drug effects Blood Vessels - abnormalities Cyclohexanes - pharmacology Humans Wnt Proteins - metabolism Models, Animal Cell Polarity - drug effects Dishevelled Proteins Cell Line Tumor Suppressor Protein p53 - metabolism Zebrafish Phosphoproteins - genetics Mutation - genetics beta Catenin - metabolism Caveolin 1 - metabolism Cell Movement - drug effects Animals Signal Transduction - drug effects Endothelial Cells - cytology Adaptor Proteins, Signal Transducing - genetics Blood Vessels - drug effects Cell Proliferation - drug effects Mice Sesquiterpenes - pharmacology Endothelial Cells - drug effects

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