Cells of the stratified adult corneal epithelium undergo centripetal migration throughout adult life from the edge of the cornea to the centre. To date nothing is known about the mechanism underpinning the oriented cellular migration. Failure to replenish apoptotic cells lost by desquamation from the superficial layer of the corneal epithelium leads to severe pathological conditions that may result in blindness. In this study we investigated the role of planar cell polarity (PCP) core proteins as the guidance cue for centripetal migration in the cornea. Cre-mediated conditional deletion of floxed alleles of the core PCP gene Vangl2 in the corneal epithelium and lens of adult mice was achieved. The effect of this deletion was studied by microscopic and immunohistological observation of the cornea compared to littermate controls, showing defects consistent with disrupted apical-basal polarity in mutant mice. Planar behaviour of the corneal epithelial cells was assayed by breeding the mutant alleles (Le-CreTg/-; Vangl2flox/flox) and the Looptail mouse (Vangl2Lp/+) onto an X-linked LacZ reporter transgene (XLacZ) background, demonstrating the importance of PCP core components for normal cell migration. In vitro directional migration studies were performed on Vangl2 and Frizzled6 knock-down human corneal epithelial cells following the application of direct current electric fields (DC-EFs), resulting in the reduction of directional migratory response to the DC-EF. This study showed for the first time roles for the planar cell polarity (PCP) signalling in orchestrating and coordinating cellular cues that drive oriented migration in the unwounded adult corneal epithelium. It is likely that mutations in PCP genes could lead to ocular surface abnormalities in humans.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:665359 |
| Date | January 2015 |
| Creators | Panzica, Domenico Alessio |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=227224 |
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