title: The core planar cell polarity gene,Vangl2, directs adult corneal epithelial cell alignment and migration.
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 cellsin vivoandin vitro. Knockdown ofVANGL2reduced 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 whichVANGL2was disrupted tended to misalign on grooved surfaces and migrate across, rather than parallel to the grooves. Adult corneal epithelial cells in whichVangl2had been conditionally deleted showed a reduced rate of wound-healing migration. Conditional deletion ofVangl2in the mouse corneal epithelium ablated the normal highly stereotyped patterns of centripetal cell migrationin vivofrom 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.
authors.affiliation: School of Medicine, Medical Sciences and Nutrition , University of Aberdeen, Institute of Medical Sciences , Aberdeen AB25 2ZD , UK.
authors.forename: Amy S
authors.initials: AS
authors.lastname: Findlay
authors.affiliation: School of Medicine, Medical Sciences and Nutrition , University of Aberdeen, Institute of Medical Sciences , Aberdeen AB25 2ZD , UK.
authors.forename: D Alessio
authors.initials: DA
authors.lastname: Panzica
authors.affiliation: School of Medicine, Medical Sciences and Nutrition , University of Aberdeen, Institute of Medical Sciences , Aberdeen AB25 2ZD , UK.
authors.forename: Petr
authors.initials: P
authors.lastname: Walczysko
authors.affiliation: School of Medicine, Medical Sciences and Nutrition , University of Aberdeen, Institute of Medical Sciences , Aberdeen AB25 2ZD , UK.
authors.forename: Amy B
authors.initials: AB
authors.lastname: Holt
authors.affiliation: Institute of Genetic Medicine , Newcastle University , Centre for Life, Newcastle upon Tyne NE1 3BZ , UK.
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Henderson
authors.affiliation: Genes and Development Group, Centre for Integrative Physiology, Clinical Sciences , University of Edinburgh Medical School , Hugh Robson Building, George Square, Edinburgh EH8 9XD , UK.
authors.forename: John D
authors.initials: JD
authors.lastname: West
authors.affiliation: School of Medicine, Medical Sciences and Nutrition , University of Aberdeen, Institute of Medical Sciences , Aberdeen AB25 2ZD , UK.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Rajnicek
authors.affiliation: School of Medicine, Medical Sciences and Nutrition , University of Aberdeen, Institute of Medical Sciences , Aberdeen AB25 2ZD , UK.
authors.forename: J Martin
authors.identifier: 0000-0002-8111-475X
authors.initials: JM
authors.lastname: Collinson
keywords: Vangl2; cell migration; cornea; epithelium; planar cell polarity