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Spatiotemporal regulation of GSK3? levels by miRNA-26a controls axon development in cortical neurons

Lucci, Cristiano; Mesquita-Ribeiro, Raquel; Rathbone, Alex; Dajas-Bailador, Federico

Spatiotemporal regulation of GSK3? levels by miRNA-26a controls axon development in cortical neurons Thumbnail


Authors

Cristiano Lucci

Alex Rathbone



Abstract

© 2020. Published by The Company of Biologists Ltd. Both the establishment of neuronal polarity and axonal growth are crucial steps in the development of the nervous system. The local translation of mRNAs in the axon provides precise regulation of protein expression, and is now known to participate in axon development, pathfinding and synaptic formation and function. We have investigated the role of miR-26a in early stage mouse primary cortical neuron development. We show that micro-RNA-26a-5p (miR-26a) is highly expressed in neuronal cultures, and regulates both neuronal polarity and axon growth. Using compartmentalised microfluidic neuronal cultures, we identified a local role for miR-26a in the axon, where the repression of local synthesis of GSK3β controls axon development and growth. Removal of this repression in the axon triggers local translation of GSK3β protein and subsequent transport to the soma, where it can impact axonal growth. These results demonstrate how the axonal miR-26a can regulate local protein translation in the axon to facilitate retrograde communication to the soma and amplify neuronal responses, in a mechanism that influences axon development.

Citation

Lucci, C., Mesquita-Ribeiro, R., Rathbone, A., & Dajas-Bailador, F. (2020). Spatiotemporal regulation of GSK3? levels by miRNA-26a controls axon development in cortical neurons. Development, 147(3), https://doi.org/10.1242/dev.180232

Journal Article Type Article
Acceptance Date Dec 19, 2019
Online Publication Date Feb 3, 2020
Publication Date Feb 3, 2020
Deposit Date Jan 8, 2020
Publicly Available Date Mar 28, 2024
Journal Development (Cambridge, England)
Print ISSN 0950-1991
Electronic ISSN 1477-9129
Publisher Company of Biologists
Peer Reviewed Peer Reviewed
Volume 147
Issue 3
Article Number dev180232
DOI https://doi.org/10.1242/dev.180232
Keywords Developmental Biology; Molecular Biology
Public URL https://nottingham-repository.worktribe.com/output/3688976
Publisher URL https://dev.biologists.org/content/early/2020/01/17/dev.180232