1. Developmental Biology
  2. Neuroscience
Download icon

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
Research Article
  • Cited 3
  • Views 1,296
  • Annotations
Cite this article as: eLife 2020;9:e51529 doi: 10.7554/eLife.51529

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.

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.

Metrics

  • 1,296
    Page views
  • 252
    Downloads
  • 3
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Developmental Biology
    Saishu Yoshida et al.
    Research Article

    Mammalian Hedgehog (Hh) signaling plays key roles in embryogenesis and uniquely requires primary cilia. Functional analyses of several ciliogenesis-related genes led to the discovery of the developmental diseases known as ciliopathies. Hence, identification of mammalian factors that regulate ciliogenesis can provide insight into the molecular mechanisms of embryogenesis and ciliopathy. Here, we demonstrate that DYRK2 acts as a novel mammalian ciliogenesis-related protein kinase. Loss of Dyrk2 in mice causes suppression of Hh signaling and results in skeletal abnormalities during in vivo embryogenesis. Deletion of Dyrk2 induces abnormal ciliary morphology and trafficking of Hh pathway components. Mechanistically, transcriptome analyses demonstrate down-regulation of Aurka and other disassembly genes following Dyrk2 deletion. Taken together, the present study demonstrates for the first time that DYRK2 controls ciliogenesis and is necessary for Hh signaling during mammalian development.

    1. Developmental Biology
    Ajun Geng et al.
    Research Article

    R-spondin1 (Rspo1) has been featured as a Wnt agonist, serving as a potent niche factor for stem cells in many tissues. Here we unveil a novel role of Rspo1 in promoting estrogen receptor alpha (Esr1) expression, hence regulating the output of steroid hormone signaling in the mouse mammary gland. This action of Rspo1 relies on the receptor Lgr4 and intracellular cAMP-PKA signaling, yet is independent of Wnt/β-catenin signaling. These mechanisms were reinforced by genetic evidence. Luminal cells-specific knockout of Rspo1 results in decreased Esr1 expression and reduced mammary side branches. In contrast, luminal cells-specific knockout of Wnt4, while attenuating basal cell Wnt/β-catenin signaling activities, enhances Esr1 expression. Our data reveal a novel Wnt-independent role of Rspo1, in which Rspo1 acts as a bona fide GPCR activator eliciting intracellular cAMP signaling. The identification of Rspo1-ERα signaling axis may have a broad implication in estrogen-associated diseases.