The Function of Vangl2 in Establishing Asymmetry in Planar Cell Polarity

Abstract

Global cell polarization, as observed in the anterior-posterior polarization of hair growth in mammalian skin cells, is a phenomenon known as planar cell polarity (PCP). A conserved characteristic of PCP in epithelial cells is the asymmetric distribution of the core PCP proteins Frizzled, Van Gogh, and Celsr. From mouse embryonic day (E) 12.5to E14.5, basal epidermal cells elongate and change shape as key PCP proteins are being asymmetrically localized. This coincides with the alignment of the actin fibers in the dermal layer as well as the alignment of dermal fibroblasts. Because of these morphological changes observed during the establishment of PCP, it was suspected that the cell elongation, alignment of dermal actin fibers, and dermal fibroblast alignment may be a cause or consequence of the asymmetric distribution of PCP components within the cell. In Looptail (Lp/Lp) mutant mice, PCP asymmetry in the epidermis is lost. By characterizing epidermal cell shape, dermal fibroblast alignment, and cytoskeletal organization in the epithelial cells of Vangl2Lp/Lp mutant mice, I have observed that the morphological changes seen during the establishment of PCP are unrelated and are not downstream mechanisms of PCP in the epidermis. In vitro studies using cultured keratinocytes show that application of a mechanical force can establish a global direction after PCP is established but is not sufficient to initiate PCP. From this, we gain a better understanding of the role Vangl2 plays in the context of PCP and how cells create asymmetric membrane domains during development.