Purchase this article with an account.
John W. McAvoy, Lucy J. Dawes, Yuki Sugiyama, Li Wen, Frank J. Lovicu; A Role for Wnt-Frizzled Signaling During FGF-induced Fiber Differentiation. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6906.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Lens fiber differentiation depends on an FGF-initiated growth factor signaling cascade. Recent studies with transgenic mice indicate that the Wnt-Frizzled (Wnt-Fz) signaling pathway is a component of this cascade and has a role in coordinating the orientation and polarity of fibers. This study set out to further investigate the relationship between the Wnt-Fz pathway and fiber differentiation.
Rat lens epithelial explants were cultured with FGF-2 to induce fiber differentiation. Inhibitors of Wnt-Fz signaling, Wnt inhibitory factor -1 (WIF-1) and Secreted frizzled-related protein (Sfrp1), were applied to assess the role of this signaling pathway in FGF-induced fiber differentiation. Immunofluorescence and Western blotting were used to study expression of components of the Wnt-Fz pathway. These techniques were also used to assess morphological and molecular features of fiber differentiation.
FGF upregulated Wnt-Fz signaling components, Fz3, Fz6, Dvl2 and Dvl3. This was accompanied by translocation of Fz from discrete membrane domains in epithelial cells to the apical tip/leading edge of each elongating fiber. Groups of fibers were also shown to be similarly polarized, as indicated by the coordinated polarization of their centrosomes. Addition of Wnt-Fz signaling inhibitors to FGF-treated explants resulted in inhibition of cell elongation and a marked reduction in expression of fiber-specific markers, filensin and ß-crystallin. Expression of Wnt-Fz signaling components was also reduced and importantly a significant reduction in the active form of Dvl2 indicated that signaling through this pathway had been inhibited.
Results from this study indicate that the Wnt-Fz pathway is a component of the FGF-induced signaling cascade that regulates the process of fiber differentiation. The results are consistent with this pathway having a key role in organizing the cytoskeleton and coordinating the polarized behaviour of lens fibers. Such organization is critical for development of the highly ordered three-dimensional lens cellular architecture.
This PDF is available to Subscribers Only