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R. J. Stump, Y. Sugiyama, A. Nguyen, F. J. Lovicu, J. W. McAvoy; Fgf Promotes Activation/Expression and Translocation of Wnt Signaling Components. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4360.
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FGF growth factor signaling is required but not sufficient for lens fiber differentiation. All the indications are that FGF initiates a growth factor signaling cascade that is required 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 activates the Wnt/PCP signaling pathway.
Western blotting was used to assess the activation/expression of Wnt signaling components, Frizzleds (Fzs) and Dishevelleds (Dvls) in lens epithelial explants treated with FGF to induce fiber differentiation. FGF-treated explants were compared with control explants (no FGF) daily over 4-days. Immunofluorescence was also used to localize Fzs, Abi2 and pericentrin (centrosome/cilium marker) in FGF-treated and control explants.
Western blotting showed that Wnt signaling components, Fz3, Dvl2 and Dvl3 were upregulated after 1-4 days exposure to FGF. 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 48 hours. FGF also promoted translocation of Fz and Abi2 to the apical tips of elongating fibers. Apical tips were identified by localization of the centromere/cilium using a pericentrin specific antibody.
FGF activates Wnt/PCP signaling during lens fiber differentiation in vitro. The translocalion of Fz and Abi2 to the apical tips of the elongating fibers in FGF-treated explants is consistent with their localization to the apical tips of cortical fibers in vivo. These results are consistent with Wnt/PCP signalling having an important role in FGF-induced fiber differentiation in vivo.
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