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J. W. McAvoy, Y. Sugiyama, R. J. W. Stump, A. Nguyen, Y. Chen, F. J. Lovicu; A Role for Wnt/planar Cell Polarity Signaling in Development of Lens Three-Dimensional Architecture. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3479.
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Lens fiber differentiation depends on an FGF-initiated growth factor signaling cascade. Studies involving overexpression of the Wnt signaling inhibitor, Sfrp2, in lenses of transgenic mice (Sfrp2+) indicate that activation of the Wnt/planar cell polarity (PCP) signaling pathway is a component of this cascade and is critical for cytoskeletal organization and development of appropriate curvature of lens fibers. To investigate this further, the relationship between alignment/orientation of fibers and location of core components of the PCP pathway was assessed in lenses of Sfrp2+ and wild-type (WT) mice.
The alignment/orientation of fibers along the equatorial plane was assessed in optical and histological sections of lenses of Sfrp2+ and WT mice (littermates). Antibodies against Frizzleds (Fz), Dishevelleds (Dvls), VanGogh-like (Vangl) and Prickle (Pk) were used to localize core Wnt/PCP signaling components in histological sections of lenses from these mice.
Compared with lenses of WT mice, which consistently show that fiber alignment and orientation is highly coordinated, fiber alignment and orientation in Sfrp2+ lenses is much more random. However, closer examination shows evidence of local order, with the orientations of groups of neighbouring fibers showing a high correlation. When such groups of fibers meet, ectopic suture-like structures or ectopic boundaries are formed. Although the fibers of Sfrp2+ mice often do not have the characteristic flattened hexagonal shape of normal fibers, they still show partitioning and reciprocal localization of PCP proteins, Fz, Dvl, Vangl and Pk, at their margins.
Overexpression of Sfrp2 disrupts global fiber polarity in the lens without destroying local polarity. These observations indicate that conserved Wnt/PCP machinery is involved in development of lens three-dimensional architecture by aligning cells and coordinating their orientation toward the anterior pole of the lens so that normal sutures form.
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