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


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.






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Publication Info

Pilaz, Louis-Jan, Kaumudi Joshi, Jing Liu, Yuji Tsunekawa, Fernando Alsina, Sahil Sethi, Ikuo Suzuki, Pierre Vanderhaeghen, et al. (2020). Subcellular mRNA localization and local translation of Arhgap11a in radial glial cells regulates cortical development. 10.1101/2020.07.30.229724 Retrieved from

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Debra Lynn Silver

Professor of Molecular Genetics and Microbiology

How is the brain assembled and sculpted during embryonic development?  Addressing this question has enormous implications for understanding neurodevelopmental disorders affecting brain size and function. In evolutionary terms, our newest brain structure is the cerebral cortex, which drives higher cognitive capacities. The overall mission of my research lab is to elucidate genetic and cellular mechanisms controlling cortical development and contributing to neurodevelopmental pathologies and brain evolution. We study neural progenitors, essential cells which generate neurons and are the root of brain development. We are guided by the premise that the same mechanisms at play during normal development were co-opted during evolution and when dysregulated, can cause neurodevelopmental disease.

My research program employs a multifaceted strategy to bridge developmental neurobiology, RNA biology, and evolution. 1) We investigate how cell fates are specified, by studying how progenitor divisions influence development and disease.  2) We study diverse layers of post-transcriptional regulation in neural progenitors. We investigate RNA binding proteins implicated in development and neurological disease. Using live imaging, we also investigate how sub-cellular control of mRNA localization and translation influences neural progenitors. 3) A parallel research focus is to understand how human-specific genetic changes influence species-specific brain development. Our goal is to integrate our efforts across these three major lines of research to understand the intricacies controlling brain development.

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