Department of Developmental and Regenerative Biology, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA.
Nat Cell Biol. 2013 Sep;15(9):1045-55. doi: 10.1038/ncb2806. Epub 2013 Aug 4.
Planar cell polarity (PCP) is cellular polarity within the plane of an epithelial tissue or organ. PCP is established through interactions of the core Frizzled (Fz)/PCP factors and, although their molecular interactions are beginning to be understood, the upstream input providing the directional bias and polarity axis remains unknown. Among core PCP genes, Fz is unique as it regulates PCP both cell-autonomously and non-autonomously, with its extracellular domain acting as a ligand for Van Gogh (Vang). We demonstrate in Drosophila melanogaster wings that Wg (Wingless) and dWnt4 (Drosophila Wnt homologue) provide instructive regulatory input for PCP axis determination, establishing polarity axes along their graded distribution and perpendicular to their expression domain borders. Loss-of-function studies reveal that Wg and dWnt4 act redundantly in PCP determination. They affect PCP by modulating the intercellular interaction between Fz and Vang, which is thought to be a key step in setting up initial polarity, thus providing directionality to the PCP process.
平面细胞极性 (PCP) 是上皮组织或器官平面内的细胞极性。PCP 通过核心卷曲 (Fz)/PCP 因子的相互作用建立，尽管它们的分子相互作用开始被理解，但提供定向偏差和极性轴的上游输入仍然未知。在核心 PCP 基因中，Fz 是独特的，因为它既可以自主地又可以非自主地调节 PCP，其细胞外结构域作为 Van Gogh (Vang) 的配体。我们在果蝇翅膀中证明，Wg（无翅）和 dWnt4（果蝇 Wnt 同源物）为 PCP 轴的确定提供了指令性调节输入，沿着它们的梯度分布建立极性轴，并垂直于它们的表达域边界。功能丧失研究表明，Wg 和 dWnt4 在 PCP 的确定中是冗余的。它们通过调节 Fz 和 Vang 之间的细胞间相互作用来影响 PCP，这被认为是建立初始极性的关键步骤，从而为 PCP 过程提供方向性。
