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R. Stump, A. Nguyen, F. J. Lovicu, J. W. McAvoy; Fgf Promotes Activation/Expression of Components of the Wnt/Planar Cell Polarity Signaling Pathway. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2787. doi: https://doi.org/.
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FGF growth factor signaling is required for lens fiber differentiation. However, studies also show a requirement for a FGF-initiated growth factor signaling cascade for fiber differentiation/maturation processes to proceed normally. Recent studies indicate that members of the Wnt growth factor family, through activation of the planar cell polarity (PCP) signaling pathway, is a critical component of this cascade. The aim of this study was to determine if FGF promoted the activation and expression of core components of the Wnt/PCP pathway.
Immunofluorescence and Western blotting was used to assess the activation/expression of Wnt signaling components, Frizzled 3 (Fz3), Dishevelled 2 and 3 (Dvl2, Dvl3), Prickle (Pk) and Scribble (Scrib), in epithelial explants from lenses of postnatal rats. Explants treated with FGF to induce fiber differentiation were compared with control explants (no FGF).
Western blotting showed that Wnt signaling components, Fz3, Dvl3, Pk and Scrib were all upregulated during FGF-induced fiber differentiation. Phosphorylation of Dvl is commonly used as a marker for activation of Wnt signalling and using an antibody that detected phosphorylated Dvl2 it was shown that FGF promoted Dvl2 phosphorylation after 24 hours. FGF also promoted redistribution of Fz3, Dvl2 and Dvl3 during fiber elongation. Interestingly, Dvl2 colocalized with actin and Dvl3 colocalized with Fz3.
These results are consistent with FGF signalling leading to activation and promotion of Wnt/PCP signaling during lens fiber differentiation. In addition colocalization of Dvl with cytoskeletal components is consistent with a role for Wnt/PCP signaling in the complex process of cytoskeletal organization during fiber differentiation.
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