Region-specific reversal of epidermal planar polarity in the rosette fancy mouse

Abstract

The planar cell polarity (PCP) pathway collectively orients cells with respect to a body axis. Hair follicles of the murine epidermis provide a striking readout of PCP activity in their uniform alignment across the skin. Here, we characterize, from the molecular to tissue-scale, PCP establishment in the fancy rosette mouse, a natural variant with posterior-specific whorls in its fur, to understand how epidermal polarity is coordinated across the tissue. We find rosette hair follicles emerge with reversed orientations specifically in the posterior region, creating a mirror image of epidermal polarity. The rosette trait is associated with a missense mutation in the core PCP gene Fzd6, which alters a consensus site for N-linked glycosylation, inhibiting its membrane localization. Unexpectedly, the Fzd6 trafficking defect does not block asymmetric localization of the other PCP proteins. Rather, the normally uniform axis of PCP asymmetry rotates where the PCP-directed cell movements that orient follicles are reversed, suggesting the PCP axis rotates 180-degrees. Collectively, our multiscale analysis of epidermal polarity reveals PCP patterning can be regionally decoupled to produce posterior whorls in the fancy rosette mouse.

Planar cell polarity is essential for the architectural patterning of the mammalian biliary tree

“…Loss or ectopic activation of PCP signalling is deleterious for normal tubular architecture, implying that cell-intrinsic levels of PCP components are critical for correct tissue patterning. In normal mammalian development, PCP proteins (including CELSR, VANGL and FZD, for example) asymmetrically localise along the proximal-distal axis of cells thereby imparting spatial information across a population of cells perpendicular to the apico-basal cell axis 13,14 . Indeed, evidence from zebrafish demonstrated that targeting PCP components pk1a , vangl2 or ankrd6 affects the development of a complex biliary tree 15 .…”