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JW McAvoy, R Stump, T von Bahr, S Ang, KI Pinson, RU de Iongh, FJ Lovicu; A Role for Wnt Signalling In Lens Epithelial Differentiation . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3885.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Members of the Wnt growth factor family regulate cell fate, adhesion, shape, proliferation, differentiation and movement, and are required for development of multiple organ systems. This study set out to investigate the role of Wnt signalling in the lens. Methods: RT-PCR was used to investigate expression of Wnt signalling molecules in capsule (with adherent epithelial cells) and fibre preparations from weanling rats. In situ hybridisation (ISH) was carried out on paraffin sections of eyes from 14-21 day old mice. Eyes of mouse embryos homozygous for a mutation in the gene coding for the LDL-related protein (LRP6), a co-factor required for Wnt signalling through the ß-catenin pathway, were examined using histology and immunofluorescence. Results: Wnt5a, Wnt7a, Wnt7b and Wnt8a were detected by RT-PCR in the lens epithelium (capsule preparation). The frizzled (Fzd) family of Wnt receptors, Fzd1, Fzd2, Fzd3, Fzd4 and Fzd10 were also detected in the epithelium. Weaker expression was generally detected in the fibres. The exception was Wnt8a which tended to be more strongly expressed in the fibres than the epithelium. ISH analysis of Wnt5a, Wnt7a, Wnt7b and Fzd4 showed expression in the epithelium and the transitional zone but no signal in differentiated fibres. RT-PCR also indicated that LRP5 and LRP6, and the intracellular signalling molecules Dishevelled (Dvl)1 and Dvl3, were also predominantly expressed in the epithelium. The Wnt signalling modulator, secreted frizzled-related protein (sFRP)1 had a similar pattern of expression. Another regulator, Dickkopf (Dkk)1, was detected in the nearby ciliary body. The LRP6 mutant had a distinctive phenotype characterised by a small eye and a lens with an incompletely formed anterior epithelium. Conclusion: The presence of molecules involved in Wnt signalling in the lens epithelium and transitional zone indicate that Wnt signalling may have a role in regulating the differentiation and behaviour of lens epithelial cells. This is supported by the absence of the central epithelium in the mice homozygous for the LRP6 mutant.
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