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Y. Sugiyama, R. J. W. Stump, A. Nguyen, F. J. Lovicu, J. W. McAvoy; A Role for Planar Cell Polarity (PCP) Signaling in Lens Fiber Differentiation Is Indicated by Asymmetric Localization of PCP Components. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4349. doi: https://doi.org/.
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Lens fiber differentiation depends on an FGF-initiated growth factor signaling cascade. Our recent studies indicate that activation of the Wnt/planar cell polarity (PCP) signaling pathway is a critical component of this cascade. To investigate this further, the lens was analyzed for key manifestations of PCP including (i) polarization of cilia and (ii) partitioning of PCP pathway components to discrete regions of cell margins.
Immunofluorescence was used to assess the localization patterns of the centromere/cilium and core Wnt/PCP signaling components in lens cells. Antibodies for Frizzleds (Fzs) Dishevelleds (Dvls), VanGogh-like (Vangl) and Prickle (Pk) were used to localize PCP proteins in whole mounts and sections of lens. Antibodies for pericentrin were used to localize centromeres/cilia. Localization of Abi2 and inversin was also included in this analysis.
Whole mounts that preserve the apical tips of fiber cells show that each cortical fibre has a centrosome/primary cilium that is polarized to the side of the cell proximal to the anterior pole of the lens. Consistent with this Fz/Vangl/Abi2 and Pk/Dvl show complementary localization patterns along the fiber cell margins. Transverse histological sections through the equatorial axis of the lens also show that, although the dimensions of the lateral sides of fibers change, Fz/Vangl/Abi2 and Pk/Dvl still show complementary localization patterns at the fiber cell margins.
Localization patterns of PCP proteins is consistent with a role for PCP signaling in promoting the alignment of fiber cells as they elongate. Furthermore, the presence of primary (sensory) cilia at the apical tips of fiber cells and their polarization to the side of the cell that faces the anterior pole is suggestive of a role in coordinating fiber cell orientation so that normal sutures are formed. This indicates a key role for the PCP pathway in the development and maintenance of lens three-dimensional architecture.
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