Examination of Wnt-family gradients and the establishment of long-range planar cell polarity in the mammalian epidermis

Abstract

Initially described an asymmetric polarization of epithelial cells along their planar axes, planar cell polarity (PCP), governs many important developmental processes to offer cells directional cues for migration and morphogenesis. Using the murine epidermis, which offers an accessible and extensive planar polarized mammalian model system, this project aims to delineate the currently unknown mechanism through which the direction of PCP is initially biased and aligned across an epithelium. Previous studies have shown that gradients of Wnt-family ligands and Fat/Dachsous pathway components are sufficient to reorient PCP within the Drosophila wing epithelium. Consistent with these observations, Fat1, Wnt5a, Wnt11 are expressed in gradients preceding the establishment of PCP along the axes of polarity in the murine epidermis. However, Wnt5a and Wnt11 knockout mice have normal PCP-dependent hair follicle polarization with the exception of muzzle guard follicles. A flow chamber was constructed and tested, and will be used to test the sufficiency of Wnt5a protein gradients to establish PCP de novo in cultured keratinocytes.