1. Developmental Biology
  2. Stem Cells and Regenerative Medicine
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Regenerative neurogenic response from glia requires insulin driven neuron-glia communication

  1. Neale J Harrison
  2. Elizabeth Connolly
  3. Alicia Gascón Gubieda
  4. Zidan Yang
  5. Benjamin Altenhein
  6. Maria Losada Perez
  7. Marta Moreira
  8. Jun Sun
  9. Alicia Hidalgo  Is a corresponding author
  1. University of Birmingham, United Kingdom
  2. University of Cologne, Germany
  3. Instituto Cajal, Consejo Superior de Investigaciones Cientificas (CSIC), Spain
Research Article
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Cite this article as: eLife 2021;10:e58756 doi: 10.7554/eLife.58756

Abstract

Understanding how injury to the Central Nervous System (CNS) induces de novo neurogenesis in animals would help promote regeneration in humans. Regenerative neurogenesis could originate from glia and glial Neuron-Glia antigen-2 (NG2) may sense injury-induced neuronal signals, but these are unknown. Here, we used Drosophila to search for genes functionally related the NG2 homologue kon-tiki (kon), and identified Islet Antigen-2 (Ia-2), required in neurons for insulin secretion. Alterations in Ia-2 function induced neural stem cell gene expression, injury increased ia-2 expression and induced ectopic neural stem cells. Using genetic analysis and lineage tracing, we demonstrate that Ia-2 and Kon regulate Drosophila insulin-like peptide 6 (Dilp-6), to induce glial proliferation and neural stem cells from glia. Ectopic neural stem cells can divide, and limited de novo neurogenesis could be traced back to glial cells. Altogether, Ia-2 and Dilp-6 drive a neuron-glia relay that restores glia, and reprograms glia into neural stem cells for regeneration.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

The following previously published data sets were used

Article and author information

Author details

  1. Neale J Harrison

    School of Biosciences, University of Birmingham, Birmingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6821-4089
  2. Elizabeth Connolly

    School of Biosciences, University of Birmingham, Birmingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Alicia Gascón Gubieda

    School of Biosciences, University of Birmingham, Birmingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Zidan Yang

    School of Biosciences, University of Birmingham, Birmingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Benjamin Altenhein

    Biocenter, University of Cologne, Cologne, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Maria Losada Perez

    Instituto Cajal, Consejo Superior de Investigaciones Cientificas (CSIC), Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
  7. Marta Moreira

    School of Biosciences, University of Birmingham, Birmingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Jun Sun

    School of Biosciences, University of Birmingham, Birmingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  9. Alicia Hidalgo

    School of Biosciences, University of Birmingham, Birmingham, United Kingdom
    For correspondence
    a.hidalgo@bham.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8041-5764

Funding

Biotechnology and Biological Sciences Research Council (BB/L008343/1)

  • Neale J Harrison
  • Marta Moreira
  • Alicia Hidalgo

Biotechnology and Biological Sciences Research Council (BB/R00871X/1)

  • Marta Moreira
  • Alicia Hidalgo

Biotechnology and Biological Sciences Research Council (MIBTP Studentship)

  • Elizabeth Connolly

Marie Curie International Incoming Post-Doctoral Fellowship (TOLKEDA)

  • Jun Sun
  • Alicia Hidalgo

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Hugo J Bellen, Baylor College of Medicine, United States

Publication history

  1. Received: May 10, 2020
  2. Accepted: February 1, 2021
  3. Accepted Manuscript published: February 2, 2021 (version 1)
  4. Version of Record published: February 12, 2021 (version 2)

Copyright

© 2021, Harrison 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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