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J.W. McAvoy, T. Reinten, R.J. W. Stump, F.J. Lovicu; A Role for Wnt/Planar Cell Polarity (PCP) Signaling in Lens Growth and Differentiation . Invest. Ophthalmol. Vis. Sci. 2004;45(13):2330.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Recent studies indicate a role for Wnt signaling in the lens. Wnt signaling appears to involve several different pathways; one of these, the Wnt/Planar Cell Polarity (PCP) pathway, characteristically regulates cell polarity and major cellular rearrangements during development. Here we aimed to determine if Wnt/PCP signaling has a role in lens development. Methods: RT–PCR and in situ hybridization were used to identify and show expression patterns of the mRNAs of molecules involved in the PCP signaling pathway, in the lens. The expression patterns of CDC42, one of the core components of the PCP pathway, was also studied by immunofluorescence on paraffin sections of lens and whole–mounts of rat lens epithelium. Rat lens epithelial explants were also applied to study the cellular distribution of the CDC42 protein and other related molecules during FGF–induced fiber differentiation. Results: RT–PCR showed the presence of a wide range of molecules involved in Wnt/PCP signaling, including core components such as the Rac, Rho and CDC42 small GTPases. In situ hybridization showed that these molecules were expressed throughout the lens epithelium and at the lens equator. Immunofluorescent localization showed that CDC42, which is known to play key roles in regulating apical–basal polarity and cell migration, was differentially distributed within the cells across the plane of the epithelium. In the central epithelium, CDC42 was located at the cell borders in association with the tight junction marker ZO–1. Equatorially, CDC42 was located throughout the cell cytoplasm, and at the onset of elongation in the transitional zone, CDC42 was strongly localized in the basal cytoplasm of these incipient fibers. In the equatorial region, CDC42 was associated with phospho–PAK, which together with CDC42 can form a direction–sensing module in migrating cells. CDC42 and phospho–PAK were also shown to be present at the leading edges of migrating and differentiating cells in FGF–treated explants. Conclusions: Elements of the PCP signaling pathway are expressed throughout the lens epithelium and at the lens equator. The relocation of CDC42 from tight junctions to the cytoplasm, particularly the basal pole of cells at the lens equator, and its association with phospho–PAK in this region, raises the possibility that directional cell migration might accompany early fiber differentiation.
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