Subcellular mRNA localization and local translation of Arhgap11a in radial glial cells regulates cortical development

Abstract

mRNA localization and local translation enable exquisite spatial and temporal control of gene expression, particularly in highly polarized and elongated cells. These features are especially prominent in radial glial cells (RGCs), which serve as neural and glial precursors of the developing cerebral cortex, and scaffolds for migrating neurons. Yet the mechanisms by which distinct sub-cellular compartments of RGCs accomplish their diverse functions are poorly understood. Here, we demonstrate that subcellular RNA localization and translation of the RhoGAP Arhgap11a controls RGC morphology and mediates cortical cytoarchitecture. Arhgap11a mRNA and protein exhibit conserved localization to RGC basal structures in mice and humans, conferred by a 5'UTR cis-element. Proper RGC morphology relies upon active Arhgap11a mRNA transport and localization to basal structures, where ARHGAP11A is locally synthesized. Thus, RhoA activity is spatially and acutely activated via local translation in RGCs to promote neuron positioning and cortical cytoarchitecture. Altogether, our study demonstrates that mRNA localization and local translation mediate compartmentalization of neural progenitor functions to control brain development. HighlightsO_LIArhgap11a in radial glia non-cell autonomously promotes neuronal migration and lamination C_LIO_LIArhgap11a mRNA localizes to radial glial endfeet via a 5 UTR cis element C_LIO_LIARHGAP11A expression in basal process and endfeet depends upon its localized mRNA C_LIO_LILocalized mRNA and RhoA-GAP activity in endfeet control radial glial morphology C_LI