Institut Curie, PSL Research University, CNRS UMR144, Paris, France.
Sorbonne University, Paris, France.
EMBO Rep. 2022 Oct 6;23(10):e54605. doi: 10.15252/embr.202254605. Epub 2022 Aug 18.
Radial glial (RG) cells are the neural stem cells of the developing neocortex. Apical RG (aRG) cells can delaminate to generate basal RG (bRG) cells, a cell type associated with human brain expansion. Here, we report that aRG delamination is regulated by the post-Golgi secretory pathway. Using in situ subcellular live imaging, we show that post-Golgi transport of RAB6+ vesicles occurs toward the minus ends of microtubules and depends on dynein. We demonstrate that the apical determinant Crumbs3 (CRB3) is also transported by dynein. Double knockout of RAB6A/A' and RAB6B impairs apical localization of CRB3 and induces a retraction of aRG cell apical process, leading to delamination and ectopic division. These defects are phenocopied by knockout of the dynein activator LIS1. Overall, our results identify a RAB6-dynein-LIS1 complex for Golgi to apical surface transport in aRG cells, and highlights the role of this pathway in the maintenance of neuroepithelial integrity.
放射状胶质细胞 (RG) 是发育中大脑皮层的神经干细胞。顶端 RG (aRG) 细胞可以分层产生基底 RG (bRG) 细胞，后者与人类大脑扩张有关。在这里，我们报告说，aRG 分层受高尔基后分泌途径的调节。通过原位亚细胞活成像，我们表明 RAB6+囊泡的高尔基后运输朝向微管的负端，并依赖于动力蛋白。我们证明，顶端决定因素 Crumb3 (CRB3) 也被动力蛋白运输。RAB6A/A' 和 RAB6B 的双敲除会损害 CRB3 的顶端定位，并诱导 aRG 细胞顶端过程的回缩，导致分层和异位分裂。这些缺陷可以通过敲除动力蛋白激活因子 Lis1 来模拟。总的来说，我们的结果确定了一个 RAB6-动力蛋白-LIS1 复合物，用于 aRG 细胞中高尔基到顶端表面的运输，并强调了该途径在维持神经上皮完整性中的作用。
