Chu Chih-Wen, Sokol Sergei Y
Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, United States.
Elife. 2016 Sep 23;5:e16463. doi: 10.7554/eLife.16463.
The coordinated orientation of cells across the tissue plane, known as planar cell polarity (PCP), is manifested by the segregation of core PCP proteins to different sides of the cell. Secreted Wnt ligands are involved in many PCP-dependent processes, yet whether they act as polarity cues has been controversial. We show that in early ectoderm, the Prickle3/Vangl2 complex was polarized to anterior cell edges and this polarity was disrupted by several Wnt antagonists. In midgastrula embryos, Wnt5a, Wnt11, and Wnt11b, but not Wnt3a, acted across many cell diameters to orient Prickle3/Vangl2 complexes away from their sources regardless of their positions relative to the body axis. The planar polarity of endogenous Vangl2 in the neuroectoderm was similarly redirected by an ectopic Wnt source and disrupted after depletion of Wnt11b in the presumptive posterior region of the embryo. These observations provide evidence for the instructive role of Wnt ligands in vertebrate PCP.
细胞在组织平面上的协同定向,即平面细胞极性(PCP),表现为核心PCP蛋白在细胞不同侧的分离。分泌型Wnt配体参与许多依赖PCP的过程,但其是否作为极性线索一直存在争议。我们发现,在早期外胚层中,Prickle3/Vangl2复合物定位于细胞前缘,这种极性被几种Wnt拮抗剂破坏。在原肠胚中期胚胎中,Wnt5a、Wnt11和Wnt11b(而非Wnt3a)作用于多个细胞直径,使Prickle3/Vangl2复合物背离其来源定向,无论其相对于身体轴的位置如何。异位Wnt源同样会重定向神经外胚层中内源性Vangl2的平面极性,且在胚胎假定后区的Wnt11b缺失后,这种极性会被破坏。这些观察结果为Wnt配体在脊椎动物PCP中的指导作用提供了证据。