Imp/IGF2BP levels modulate individual neural stem cell growth and division through myc mRNA stability
Abstract
The numerous neurons and glia that form the brain originate from tightly controlled growth and division of neural stem cells, regulated systemically by important known stem cell-extrinsic signals. However, the cell-intrinsic mechanisms that control the distinctive proliferation rates of individual neural stem cells are unknown. Here, we show that the size and division rates of Drosophila neural stem cells (neuroblasts) are controlled by the highly conserved RNA binding protein Imp (IGF2BP), via one of its top binding targets in the brain, myc mRNA. We show that Imp stabilises myc mRNA leading to increased Myc protein levels, larger neuroblasts, and faster division rates. Declining Imp levels throughout development limit myc mRNA stability to restrain neuroblast growth and division, and heterogeneous Imp expression correlates with myc mRNA stability between individual neuroblasts in the brain. We propose that Imp-dependent regulation of myc mRNA stability fine-tunes individual neural stem cell proliferation rates.
Data availability
The presented RNA sequencing data has been deposited with Gene Expression Omnibus (GEO), with accession number GSE140704.
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Imp/IGF2BP levels modulate individual neural stem cell growth and division through myc mRNA stabilityNCBI Gene Expression Omnibus, GSE140704.
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Drosophila Imp iCLIP identifies an RNA assemblage co-ordinating F-actin formationNCBI Gene Expression Omnibus, GSE62997.
Article and author information
Author details
Funding
Wellcome (105363/Z/14/Z)
- Tamsin J Samuels
Wellcome (096144/Z/17/Z)
- Aino I Järvelin
- Ilan Davis
Wellcome (209412/Z/17/Z)
- Tamsin J Samuels
- Aino I Järvelin
- Ilan Davis
University College London
- David Ish-Horowicz
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Claude Desplan, New York University, United States
Version history
- Received: August 31, 2019
- Accepted: January 13, 2020
- Accepted Manuscript published: January 14, 2020 (version 1)
- Version of Record published: February 17, 2020 (version 2)
Copyright
© 2020, Samuels et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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