Neurons require proper polarization for precise positioning and axon-dendrite formation. Their intrinsic regulators and underlying mechanisms are poorly understood. Here, we show that Wdr47 is a key polarization regulator. Wdr47-deficient newborn mice die of suffocation due to central nervous system defects including axonal tracts agenesis and slowed radial migration. Wdr47 deficiency represses the multipolar-bipolar transition of cortical neurons, reduces neurite tip-directed microtubule dynamics, and causes multi-axon formation. Overexpression of Wdr47 in wild-type neurons inhibits axon specification and neutralizes Taxol-induced neurite overgrowth and axon overproduction. Wdr47 interacts with the Camsap family of microtubule minus-end-binding proteins; associates with microtubules through Camsap3, whose gene disruption also causes multi-axons; and promotes Camsap3 accumulation in neurites of unpolarized neurons. Furthermore, Camsap overexpression rescues the polarization defects of Wdr47-deficient neurons. Our results indicate that Wdr47 facilitates proper neurite remodeling through Camsaps to fine-tune regional microtubule dynamics and organization during early stages of neuronal polarization.

中文翻译：

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Wdr47通过Camsap家族微管负末端结合蛋白控制神经元极化。

神经元需要适当的极化才能精确定位并形成轴突-树突。他们内在的调节器和潜在的机制了解甚少。在这里，我们表明Wdr47是关键的偏振调节器。缺乏Wdr47的新生小鼠由于中枢神经系统缺陷（包括轴突束发育不全和径向迁移减慢）而窒息死亡。Wdr47缺乏抑制了皮质神经元的多极-双极过渡，减少了神经突尖端定向的微管动力学，并导致了多轴突形成。Wdr47在野生型神经元中的过表达抑制轴突的规格并中和紫杉醇诱导的神经突过度生长和轴突过度产生。Wdr47与Camsap家族的微管负末端结合蛋白相互作用。通过Camsap3与微管结合，其基因破坏也引起多轴突。并促进Camsap3在非极化神经元的神经突中积累。此外，Camsap的过表达可以挽救Wdr47缺陷型神经元的极化缺陷。我们的结果表明Wdr47有助于通过Camsaps进行适当的神经突重塑，以在神经元极化的早期阶段微调区域微管动力学和组织。