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The core planar cell polarity gene, Vangl2, directs adult corneal epithelial cell alignment and migration

Lookup NU author(s): Professor Deborah HendersonORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

This study shows that the core planar cell polarity (PCP) genes direct the aligned cell migration in the adult corneal epithelium, a stratified squamous epithelium on the outer surface of the vertebrate eye. Expression of multiple core PCP genes was demonstrated in the adult corneal epithelium. PCP components were manipulated genetically and pharmacologically in human and mouse corneal epithelial cells in vivo and in vitro. Knockdown of VANGL2 reduced the directional component of migration of human corneal epithelial (HCE) cells without affecting speed. It was shown that signalling through PCP mediators, dishevelled, dishevelled-associated activator of morphogenesis and Rho-associated protein kinase directs the alignment of HCE cells by affecting cytoskeletal reorganization. Cells in which VANGL2 was disrupted tended to misalign on grooved surfaces and migrate across, rather than parallel to the grooves. Adult corneal epithelial cells in which Vangl2 had been conditionally deleted showed a reduced rate of wound-healing migration. Conditional deletion of Vangl2 in the mouse corneal epithelium ablated the normal highly stereotyped patterns of centripetal cell migration in vivo from the periphery (limbus) to the centre of the cornea. Corneal opacity owing to chronic wounding is a major cause of degenerative blindness across the world, and this study shows that Vangl2 activity is required for directional corneal epithelial migration.


Publication metadata

Author(s): Findlay AS, Panzica DA, Walczysko P, Holt AB, Henderson DJ, West JD, Rajnicek A, Collinson JM

Publication type: Article

Publication status: Published

Journal: Royal Society Open Science

Year: 2016

Volume: 3

Issue: 10

Online publication date: 19/10/2016

Acceptance date: 15/09/2016

Date deposited: 10/02/2017

ISSN (electronic): 2054-5703

Publisher: Royal Society Publishing

URL: http://dx.doi.org/10.1098/rsos.160658

DOI: 10.1098/rsos.160658


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Funding

Funder referenceFunder name
Anatomical Society PhD Studentship ('The Roles of planar cell polarity genes in a classical anatomical system: the cornea')
Biotechnology and Biological Sciences Research Council (BBSRC)
BB/J015172/1BBSRC Project
BB/J015237/1BBSRC Project

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