近日，德国神经退行性疾病中心Frank Bradke及其小组的最新研究提出了内在细胞骨架振荡器确立神经元极性。这一研究成果发表在2026年7月8日出版的国际学术期刊《自然》上。

据了解，神经元通过将一个神经突起指定为轴突来获得极性，而其他神经突起则变成树突。但这种基本的不对称性是如何建立的仍不清楚。神经元极化被认为主要依赖于感知外部线索的生长锥。在这里，小组表明生长锥本身并不能指导这一过程，而体细胞是神经元极化的中心组织者。利用活体成像和遗传功能丧失方法，结合光遗传学控制和培养神经元的局部细胞骨架扰动，该团队发现了一个由体细胞启动的振荡程序，该程序启动了轴突选择。

依赖于胞体中肌动蛋白相关蛋白2/3 （ARP2/3）复合体的周期性肌动蛋白分支重塑了一个全局的肌动球蛋白网络，从而产生一个肌动蛋白波，在传播到单个神经突尖端之前收缩神经突。暴露于这种波会使局部肌动球蛋白收缩性放松，从而导致短暂的基于微管的突起，并使神经突倾向于轴突的命运。当细胞退出这个振荡阶段时，这个神经突可以克服全局抑制并独立于ARP2/3延伸，而肌动球蛋白活性抑制剩余神经突的轴突形成，使它们随后成为树突。这种由体细胞驱动的机制确保了一个独立于环境信号的轴突的出现，并支撑了神经元回路中的单向信息流。

附：英文原文

Title: An intrinsic cytoskeletal oscillator establishes neuronal polarity

Author: Lin, Tien-chen, Coles, Charlotte H., Alfadil, Eissa, Fler, Florian, Husch, Andreas, Dupraz, Sebastian, Pietralla, Thorben, Narita, Akihiro, Schelski, Max, Flynn, Kevin C., Stern, Sina, Mhl, Christoph, Hilton, Brett J., Vauti, Franz, Arnold, Hans-Henning, Schur, Florian K. M., Bradke, Frank

Issue&Volume: 2026-07-08

Abstract: Neurons acquire polarity by specifying one neurite as the axon, whereas the others become dendrites. But how this fundamental asymmetry is established remains unclear1. Neuronal polarization has been thought to rely primarily on growth cones that sense external cues2. Here we show that growth cones alone do not direct this process and that the soma acts as a central organizer of neuronal polarization. Using live imaging and genetic loss-of-function approaches in vivo, combined with optogenetic control and local cytoskeletal perturbations in cultured neurons, we uncover a soma-initiated oscillatory program that primes axon selection. Periodic actin branching that depends on the actin-related protein 2/3 (ARP2/3) complex at the soma remodels a global actomyosin network, thereby generating an actin wave that retracts neurites before propagating into a single neurite tip. Exposure to this wave relaxes local actomyosin contractility, which drives a transient microtubule-based protrusion and biases this neurite towards axon fate. As the cell exits this oscillatory stage, this neurite can overcome global inhibition and extend independently of ARP2/3, whereas actomyosin activity suppresses axon formation in the remaining neurites so that they subsequently become dendrites. This soma-driven mechanism ensures the emergence of a single axon independent of environmental cues and underpins the unidirectional information flow in neuronal circuits.

DOI: 10.1038/s41586-026-10755-6

Source: https://www.nature.com/articles/s41586-026-10755-6

期刊信息

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504

官方网址：http://www.nature.com/

投稿链接：http://www.nature.com/authors/submit_manuscript.html