Technical University of Braunschweig, Zoological Institute, Cellular and Molecular Neurobiology, Braunschweig, Germany.
University of Bern, Institute of Anatomy, Bern, Switzerland.
J Cell Biol. 2020 Oct 5;219(10). doi: 10.1083/jcb.201908040.
Neuronal migration during development is necessary to form an ordered and functional brain. Postmitotic neurons require microtubules and dynein to move, but the mechanisms by which they contribute to migration are not fully characterized. Using tegmental hindbrain nuclei neurons in zebrafish embryos together with subcellular imaging, optogenetics, and photopharmacology, we show that, in vivo, the centrosome's position relative to the nucleus is not linked to greatest motility in this cell type. Nevertheless, microtubules, dynein, and kinesin-1 are essential for migration, and we find that interference with endosome formation or the Golgi apparatus impairs migration to a similar extent as disrupting microtubules. In addition, an imbalance in the traffic of the model cargo Cadherin-2 also reduces neuronal migration. These results lead us to propose that microtubules act as cargo carriers to control spatiotemporal protein distribution, which in turn controls motility. This adds crucial insights into the variety of ways that microtubules can support successful neuronal migration in vivo.
在发育过程中，神经元迁移对于形成有序且功能正常的大脑是必要的。有丝分裂后神经元需要微管和动力蛋白来移动，但它们对迁移的贡献机制尚未完全阐明。本研究利用斑马鱼胚胎的脑桥中脑神经核神经元，结合亚细胞成像、光遗传学和光药理学，结果表明，在体内，中心体相对于细胞核的位置与该细胞类型的最大迁移性无关。尽管如此，微管、动力蛋白和驱动蛋白-1对于迁移是必不可少的，我们发现，干扰内体形成或高尔基体同样会损害迁移，其程度与破坏微管相似。此外，模型货物 Cadherin-2 的运输失衡也会减少神经元迁移。这些结果使我们提出，微管作为货物载体来控制时空蛋白质分布，从而控制运动。这为微管在体内支持成功的神经元迁移的多种方式提供了关键见解。
