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

Amy S. Findlay, D. Alessio Panzica, Petr Walczysko, Amy B. Holt, Deborah J. Henderson, John D. West, Ann M. Rajnicek, J. Martin Collinson

Research output: Contribution to journalArticle

7 Citations (Scopus)
5 Downloads (Pure)

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.
Original languageEnglish
Article number160658
JournalRoyal Society Open Science
Volume3
Early online date19 Oct 2016
DOIs
Publication statusPublished - Oct 2016

Fingerprint

Cell Polarity
Corneal Epithelium
Epithelial Cells
Genes
Cell Movement
Corneal Opacity
rho-Associated Kinases
Cellular Structures
Blindness
Morphogenesis
Wound Healing
Cornea
Protein Kinases
Vertebrates
Epithelium

Keywords

  • cornea
  • epithelium
  • planar cell polarity
  • Vangl2
  • cell migration

Cite this

The core planar cell polarity gene, Vangl2, directs adult corneal epithelialcell alignment and migration. / Findlay, Amy S.; Panzica, D. Alessio; Walczysko, Petr; Holt, Amy B.; Henderson, Deborah J. ; West, John D.; Rajnicek, Ann M.; Collinson, J. Martin.

In: Royal Society Open Science, Vol. 3, 160658, 10.2016.

Research output: Contribution to journalArticle

Findlay, Amy S. ; Panzica, D. Alessio ; Walczysko, Petr ; Holt, Amy B. ; Henderson, Deborah J. ; West, John D. ; Rajnicek, Ann M. ; Collinson, J. Martin. / The core planar cell polarity gene, Vangl2, directs adult corneal epithelialcell alignment and migration. In: Royal Society Open Science. 2016 ; Vol. 3.
@article{5cafd7adfa8f43f38d7f9614a8449a16,
title = "The core planar cell polarity gene, Vangl2, directs adult corneal epithelialcell 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 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.",
keywords = "cornea, epithelium , planar cell polarity, Vangl2 , cell migration",
author = "Findlay, {Amy S.} and Panzica, {D. Alessio} and Petr Walczysko and Holt, {Amy B.} and Henderson, {Deborah J.} and West, {John D.} and Rajnicek, {Ann M.} and Collinson, {J. Martin}",
note = "This work was supported by a Biotechnology and Biological Sciences Research Council (BBSRC) DTG PhD studentship to A.F., an Anatomical Society PhD Studentship (‘The Roles of planar cell polarity genes in a classical anatomical system: the cornea’) to D.A.P./J.M.C. and BBSRC Project Grants BB/J015172/1 and BB/J015237/1 to J.D.W. and J.M.C., respectively.",
year = "2016",
month = "10",
doi = "10.1098/rsos.160658",
language = "English",
volume = "3",
journal = "Royal Society Open Science",
issn = "2054-5703",
publisher = "The Royal Society",

}

TY - JOUR

T1 - The core planar cell polarity gene, Vangl2, directs adult corneal epithelialcell alignment and migration

AU - Findlay, Amy S.

AU - Panzica, D. Alessio

AU - Walczysko, Petr

AU - Holt, Amy B.

AU - Henderson, Deborah J.

AU - West, John D.

AU - Rajnicek, Ann M.

AU - Collinson, J. Martin

N1 - This work was supported by a Biotechnology and Biological Sciences Research Council (BBSRC) DTG PhD studentship to A.F., an Anatomical Society PhD Studentship (‘The Roles of planar cell polarity genes in a classical anatomical system: the cornea’) to D.A.P./J.M.C. and BBSRC Project Grants BB/J015172/1 and BB/J015237/1 to J.D.W. and J.M.C., respectively.

PY - 2016/10

Y1 - 2016/10

N2 - 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.

AB - 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.

KW - cornea

KW - epithelium

KW - planar cell polarity

KW - Vangl2

KW - cell migration

U2 - 10.1098/rsos.160658

DO - 10.1098/rsos.160658

M3 - Article

VL - 3

JO - Royal Society Open Science

JF - Royal Society Open Science

SN - 2054-5703

M1 - 160658

ER -