Findlay Amy S, Panzica D Alessio, Walczysko Petr, Holt Amy B, Henderson Deborah J, West John D, Rajnicek Ann M, Collinson J Martin
School of Medicine, Medical Sciences and Nutrition , University of Aberdeen, Institute of Medical Sciences , Aberdeen AB25 2ZD , UK.
Institute of Genetic Medicine , Newcastle University , Centre for Life, Newcastle upon Tyne NE1 3BZ , UK.
R Soc Open Sci. 2016 Oct 19;3(10):160658. doi: 10.1098/rsos.160658. eCollection 2016 Oct.
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 and . Knockdown of 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 was disrupted tended to misalign on grooved surfaces and migrate across, rather than parallel to the grooves. Adult corneal epithelial cells in which had been conditionally deleted showed a reduced rate of wound-healing migration. Conditional deletion of in the mouse corneal epithelium ablated the normal highly stereotyped patterns of centripetal cell migration 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.
本研究表明,核心平面细胞极性(PCP)基因指导成年角膜上皮细胞的定向迁移,角膜上皮是脊椎动物眼睛外表面的复层鳞状上皮。在成年角膜上皮中证实了多个核心PCP基因的表达。在人和小鼠角膜上皮细胞中对PCP成分进行了基因和药理学操作。敲低[具体基因名称未给出]可降低人角膜上皮(HCE)细胞迁移的定向成分,而不影响速度。结果表明,通过PCP介质、蓬乱蛋白、形态发生相关蓬乱蛋白激活剂和Rho相关蛋白激酶发出的信号,通过影响细胞骨架重组来指导HCE细胞的排列。[具体基因名称未给出]被破坏的细胞在有凹槽的表面上往往排列不齐,并会穿过凹槽迁移,而不是平行于凹槽迁移。条件性缺失[具体基因名称未给出]的成年角膜上皮细胞显示伤口愈合迁移率降低。在小鼠角膜上皮中条件性缺失[具体基因名称未给出]消除了从周边(角膜缘)向角膜中心的正常高度定型的向心细胞迁移模式。由于慢性创伤导致的角膜混浊是全球退行性失明的主要原因,本研究表明Vangl2活性是角膜上皮定向迁移所必需的。