RAB6 and dynein drive post-Golgi apical transport to prevent neuronal progenitor delamination

RAB6 和动力蛋白驱动高尔基体后的顶端运输,以防止神经元祖细胞脱离细胞层。

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作者:Jean-Baptiste Brault ,Sabine Bardin ,Marusa Lampic ,Jacopo A Carpentieri ,Laure Coquand ,Maxime Penisson ,Hugo Lachuer ,Guiliana Soraya Victoria ,Sarah Baloul ,Fatima El Marjou ,Gaelle Boncompain ,Stephanie Miserey-Lenkei ,Richard Belvindrah ,Vincent Fraisier ,Fiona Francis ,Franck Perez ,Bruno Goud ,Alexandre D Baffet

Abstract

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.

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