The core planar cell polarity gene, Vangl2, directs adult corneal epithelial cell alignment and migration.
The core planar cell polarity gene, Vangl2, directs adult corneal epithelial cell alignment and migration.
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DOI：
10.1098/rsos.160658
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发表时间：
2016-10
影响因子：
3.5
通讯作者：
Collinson JM
中科院分区：
文献类型：
--
作者：
Findlay AS;Panzica DA;Walczysko P;Holt AB;Henderson DJ;West JD;Rajnicek AM;Collinson JM
这项研究表明，核心平面细胞极性(PCP)基因指导着成体角膜上皮中排列的细胞迁移，成体角膜上皮是脊椎动物眼睛外表面的一种复层鳞状上皮。多个核心PCP基因在成人角膜上皮细胞中表达。在体内和体外，PCP组分在人和小鼠角膜上皮细胞中进行了遗传和药理方面的操作。Vangl2基因的敲除减少了人角膜上皮(HCE)细胞迁移的方向性成分，而不影响速度。研究表明，通过PCP介质、蓬乱的、蓬乱的形态发生相关激活物和Rho相关的蛋白激酶的信号转导，通过影响细胞骨架的重组来指导HCE细胞的排列。Vangl2被破坏的细胞倾向于在凹槽表面错位并迁移，而不是平行于凹槽。在成年角膜上皮细胞中，Vangl2被有条件地删除后，伤口愈合移行率降低。有条件地删除小鼠角膜上皮中的Vangl2基因，消融了体内向心细胞从角膜边缘向中心迁移的正常的高度定型的模式。慢性创伤引起的角膜混浊是全世界退行性失明的一个主要原因，本研究表明，Vangl2活性是角膜上皮定向迁移所必需的。
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.
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影响因子：
14
作者：
Evans, MDM;McFarland, GA;Walboomers, XF
通讯作者：
Walboomers, XF
影响因子：
3.4
作者：
Feng, Yun;Foster, James;Connon, Che John
通讯作者：
Connon, Che John
影响因子：
16.6
作者：
Lobo EP;Delic NC;Richardson A;Raviraj V;Halliday GM;Di Girolamo N;Myerscough MR;Lyons JG
通讯作者：
Lyons JG
影响因子：
3.7
作者：
Dorà NJ;Collinson JM;Hill RE;West JD
通讯作者：
West JD
影响因子：
1.2
作者：
Dorà NJ;Hill RE;Collinson JM;West JD
通讯作者：
West JD