Laboratory of Axon Growth and Regeneration, German Center for Neurodegenerative Diseases (DZNE), Venusberg-Campus 1, Building 99, 53127 Bonn, Germany.
Department of Health Sciences and Technology, ETH Zürich, Otto-Stern-Weg 7, 8093 Zürich, Switzerland.
Cell Rep. 2020 Jul 21;32(3):107907. doi: 10.1016/j.celrep.2020.107907.
During development of the central nervous system (CNS), neurons polarize and rapidly extend their axons to assemble neuronal circuits. The growth cone leads the axon to its target and drives axon growth. Here, we explored the mechanisms underlying axon growth in three dimensions. Live in situ imaging and super-resolution microscopy combined with pharmacological and molecular manipulations as well as biophysical force measurements revealed that growth cones extend CNS axons independent of pulling forces on their substrates and without the need for adhesions in three-dimensional (3D) environments. In 3D, microtubules grow unrestrained from the actomyosin cytoskeleton into the growth cone leading edge to enable rapid axon extension. Axons extend and polarize even in adhesion-inert matrices. Thus, CNS neurons use amoeboid mechanisms to drive axon growth. Together with our understanding that adult CNS axons regenerate by reactivating developmental processes, our findings illuminate how cytoskeletal manipulations enable axon regeneration in the adult CNS.
在中枢神经系统 (CNS) 的发育过程中，神经元极化并迅速延伸其轴突以组装神经元回路。生长锥引导轴突到达其靶标并驱动轴突生长。在这里，我们探索了三维空间中轴突生长的机制。活的原位成像和超分辨率显微镜结合药理学和分子操作以及生物物理力测量表明，生长锥在三维 (3D) 环境中独立于其基质上的拉力延伸 CNS 轴突，而无需粘附。在 3D 中，微管从肌动球蛋白细胞骨架不受限制地生长到生长锥前缘，从而实现快速轴突延伸。轴突甚至在无粘附性的基质中延伸和极化。因此，中枢神经系统神经元使用变形虫机制来驱动轴突生长。结合我们对成年中枢神经系统轴突通过重新激活发育过程进行再生的理解，我们的发现阐明了细胞骨架操作如何使成年中枢神经系统中的轴突再生。
