1. Developmental Biology
  2. Neuroscience
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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 6
  • Views 1,616
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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.

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Further reading

    1. Developmental Biology
    Junjun Jing et al.
    Research Article

    Interaction between adult stem cells and their progeny is critical for tissue homeostasis and regeneration. In multiple organs, mesenchymal stem cells (MSCs) give rise to transit amplifying cells (TACs), which then differentiate into different cell types. However, whether and how MSCs interact with TACs remains unknown. Using the adult mouse incisor as a model, we present in vivo evidence that TACs and MSCs have distinct genetic programs and engage in reciprocal signaling cross talk to maintain tissue homeostasis. Specifically, an IGF-WNT signaling cascade is involved in the feedforward from MSCs to TACs. TACs are regulated by tissue-autonomous canonical WNT signaling and can feedback to MSCs and regulate MSC maintenance via Wnt5a/Ror2-mediated non-canonical WNT signaling. Collectively, these findings highlight the importance of coordinated bidirectional signaling interaction between MSCs and TACs in instructing mesenchymal tissue homeostasis, and the mechanisms identified here have important implications for MSC–TAC interaction in other organs.

    1. Developmental Biology
    2. Neuroscience
    Maria Schörnig et al.
    Research Article

    We generated induced excitatory neurons (iNeurons, iNs) from chimpanzee, bonobo and human stem cells by expressing the transcription factor neurogenin‑2 (NGN2). Single cell RNA sequencing (scRNAseq) showed that genes involved in dendrite and synapse development are expressed earlier during iNs maturation in the chimpanzee and bonobo than the human cells. In accordance, during the first two weeks of differentiation, chimpanzee and bonobo iNs showed repetitive action potentials and more spontaneous excitatory activity than human iNs, and extended neurites of higher total length. However, the axons of human iNs were slightly longer at 5 weeks of differentiation. The timing of the establishment of neuronal polarity did not differ between the species. Chimpanzee, bonobo and human neurites eventually reached the same level of structural complexity. Thus, human iNs develop slower than chimpanzee and bonobo iNs and this difference in timing likely depends on functions downstream of NGN2.