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

Louis-Jan Pilaz, Kaumudi Joshi, Jing Liu, Yuji Tsunekawa, Fernando C. Alsina, Sahil Sethi, Ikuo K. Suzuki, Pierre Vanderhaeghen, View ORCID ProfileFranck Polleux, View ORCID ProfileDebra L. Silver
doi: https://doi.org/10.1101/2020.07.30.229724
Louis-Jan Pilaz
1Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710 USA
2Pediatrics and Rare Diseases Group, Sanford Research, Sioux Falls, SD 57104 USA
3Department of Pediatrics, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD 57105 USA
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Kaumudi Joshi
4Department of Neuroscience, Columbia University Medical Center, New York, NY, USA
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Jing Liu
1Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710 USA
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Yuji Tsunekawa
5Laboratory for Cell Asymmetry, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan
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Fernando C. Alsina
1Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710 USA
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Sahil Sethi
1Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710 USA
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Ikuo K. Suzuki
6Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan
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Pierre Vanderhaeghen
7VIB-KU Leuven Center for Brain & Disease Research, 3000 Leuven, Belgium
8KU Leuven, Department of Neurosciences & Leuven Brain Institute, 3000 Leuven, Belgium
9Université Libre de Bruxelles (U.L.B.), Institut de Recherches en Biologie Humaine et Moléculaire (IRIBHM), and ULB Neuroscience Institute (UNI), 1070 Brussels, Belgium
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Franck Polleux
4Department of Neuroscience, Columbia University Medical Center, New York, NY, USA
10Mortimer B. Zuckerman Mind Brain Behavior Institute, New York, NY USA
11Kavli Institute for Brain Sciences, Columbia University Medical Center, New York, NY USA
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Debra L. Silver
1Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710 USA
12Departments of Cell Biology and Neurobiology, Duke University Medical Center, Durham, NC 27710 USA
13Duke Institute for Brain Sciences, Duke University Medical Center, Durham, NC 27710 USA
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  • ORCID record for Debra L. Silver
  • For correspondence: debra.silver@duke.edu
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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.

Highlights

  • Arhgap11a in radial glia non-cell autonomously promotes neuronal migration and lamination

  • Arhgap11a mRNA localizes to radial glial endfeet via a 5’ UTR cis element

  • ARHGAP11A expression in basal process and endfeet depends upon its localized mRNA

  • Localized mRNA and RhoA-GAP activity in endfeet control radial glial morphology

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted July 31, 2020.
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Subcellular mRNA localization and local translation of Arhgap11a in radial glial cells regulates cortical development
Louis-Jan Pilaz, Kaumudi Joshi, Jing Liu, Yuji Tsunekawa, Fernando C. Alsina, Sahil Sethi, Ikuo K. Suzuki, Pierre Vanderhaeghen, Franck Polleux, Debra L. Silver
bioRxiv 2020.07.30.229724; doi: https://doi.org/10.1101/2020.07.30.229724
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Subcellular mRNA localization and local translation of Arhgap11a in radial glial cells regulates cortical development
Louis-Jan Pilaz, Kaumudi Joshi, Jing Liu, Yuji Tsunekawa, Fernando C. Alsina, Sahil Sethi, Ikuo K. Suzuki, Pierre Vanderhaeghen, Franck Polleux, Debra L. Silver
bioRxiv 2020.07.30.229724; doi: https://doi.org/10.1101/2020.07.30.229724

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