Imp/IGF2BP levels modulate individual neural stem cell growth and division through myc mRNA stability

  1. Tamsin J Samuels
  2. Aino I Järvelin
  3. David Ish-Horowicz
  4. Ilan Davis  Is a corresponding author
  1. University of Oxford, United Kingdom
  2. University College London, United Kingdom

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.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Tamsin J Samuels

    Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Aino I Järvelin

    Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. David Ish-Horowicz

    MRC Laboratory for Molecular Cell Biology, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Ilan Davis

    Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    For correspondence
    ilan.davis@bioch.ox.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5385-3053

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

  1. Claude Desplan, New York University, United States

Publication history

  1. Received: August 31, 2019
  2. Accepted: January 13, 2020
  3. Accepted Manuscript published: January 14, 2020 (version 1)
  4. 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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  1. Tamsin J Samuels
  2. Aino I Järvelin
  3. David Ish-Horowicz
  4. Ilan Davis
(2020)
Imp/IGF2BP levels modulate individual neural stem cell growth and division through myc mRNA stability
eLife 9:e51529.
https://doi.org/10.7554/eLife.51529
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