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顶端运输,防止神经元祖细胞分层

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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

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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