Departments of Biochemistry and Molecular Biology, Sciences II, 30 Quai Ernest-Ansermet, CH-1211 Geneva 4, Switzerland.
Nat Cell Biol. 2013 Jan;15(1):28-39. doi: 10.1038/ncb2632. Epub 2012 Dec 2.
Oriented mitosis is essential during tissue morphogenesis. The Wnt/planar cell polarity (Wnt/PCP) pathway orients mitosis in a number of developmental systems, including dorsal epiblast cell divisions along the animal-vegetal (A-V) axis during zebrafish gastrulation. How Wnt signalling orients the mitotic plane is, however, unknown. Here we show that, in dorsal epiblast cells, anthrax toxin receptor 2a (Antxr2a) accumulates in a polarized cortical cap, which is aligned with the embryonic A-V axis and forecasts the division plane. Filamentous actin (F-actin) also forms an A-V polarized cap, which depends on Wnt/PCP and its effectors RhoA and Rock2. Antxr2a is recruited to the cap by interacting with actin. Antxr2a also interacts with RhoA and together they activate the diaphanous-related formin zDia2. Mechanistically, Antxr2a functions as a Wnt-dependent polarized determinant, which, through the action of RhoA and zDia2, exerts torque on the spindle to align it with the A-V axis.
有丝分裂取向对于组织形态发生至关重要。Wnt/平面细胞极性（Wnt/PCP）途径在许多发育系统中使有丝分裂取向，包括斑马鱼原肠胚形成过程中沿动物-植物（A-V）轴的背侧外胚层细胞分裂。然而，Wnt 信号如何使有丝分裂平面取向尚不清楚。在这里，我们表明，在背侧外胚层细胞中，炭疽毒素受体 2a（Antxr2a）在与胚胎 A-V 轴对齐并预测分裂平面的极化皮质帽中积累。丝状肌动蛋白（F-actin）也形成 A-V 极化帽，这取决于 Wnt/PCP 及其效应物 RhoA 和 Rock2。Antxr2a 通过与肌动蛋白相互作用被募集到帽中。Antxr2a 还与 RhoA 相互作用，它们共同激活与 diaphanous 相关的形成素 zDia2。在机制上，Antxr2a 作为一种依赖于 Wnt 的极化决定因素发挥作用，通过 RhoA 和 zDia2 的作用，对纺锤体施加扭矩使其与 A-V 轴对齐。
