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Lookup NU author(s): Professor Deborah HendersonORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
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.
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
Online publication date: 19/10/2016
Acceptance date: 15/09/2016
Date deposited: 10/02/2017
ISSN (electronic): 2054-5703
Publisher: Royal Society Publishing
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