Regenerative neurogenic response from glia requires insulin driven neuron-glia communication
- University of Birmingham, United Kingdom
- University of Cologne, Germany
- Instituto Cajal, Consejo Superior de Investigaciones Cientificas (CSIC), Spain
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.
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Single cell transcriptome atlas of the Drosophila larval brainNCBI Gene Expression Omnibus, GSE134722.
Article and author information
Author details
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.
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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Regenerative neurogenic response from glia requires insulin driven neuron-glia communication
eLife 10:e58756.
https://doi.org/10.7554/eLife.58756
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