Department of Genetics, Cell Biology and Development, University of Minnesota Twin Cities, Minneapolis, MN 55455, USA.
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08540, USA.
Development. 2023 Sep 1;150(17). doi: 10.1242/dev.202078. Epub 2023 Sep 7.
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 rosette fancy mouse, a natural variant with posterior-specific whorls in its fur, to understand how epidermal polarity is coordinated across the tissue. We find that 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°. Collectively, our multiscale analysis of epidermal polarity reveals PCP patterning can be regionally decoupled to produce posterior whorls in the rosette fancy mouse.
平面细胞极性 (PCP) 通路集体使细胞相对于身体轴定向。鼠表皮的毛囊在其沿皮肤的均匀排列中提供了 PCP 活性的明显读出。在这里，我们从分子到组织尺度上，对罗塞特花式小鼠的 PCP 建立进行了表征，这是一种天然变体，其毛发在后侧具有特定的涡旋，以了解如何协调整个组织的表皮极性。我们发现罗塞特毛囊在前部区域以特定的反向方向出现，从而在表皮极性中创建镜像。罗塞特特征与核心 PCP 基因 Fzd6 的错义突变相关，该突变改变了 N 连接糖基化的保守位点，从而抑制其膜定位。出人意料的是，Fzd6 的运输缺陷并不阻止其他 PCP 蛋白的不对称定位。相反，通常均匀的 PCP 不对称轴旋转，定向毛囊的 PCP 定向细胞运动被反转，这表明 PCP 轴旋转 180°。总的来说，我们对表皮极性的多尺度分析揭示了 PCP 模式可以在局部解耦，从而在罗塞特花式小鼠中产生后部涡旋。
