Regenerative neurogenic response from glia requires insulin driven neuron-glia communication

Neale Harrison, Elizabeth Connolly, Alicia Gascón Gubieda, Zidan Yang, Benjamin Altenhein, Maria Losada-Perez, Marta Moreira, Jun Sun, Alicia Hidalgo

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Understanding how injury to the central nervous system 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 to the NG2 homologue kon-tiki (kon), and identified Islet Antigen-2 (Ia-2), required in neurons for insulin secretion. Both loss and over-expression of ia-2 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 reprogrammes glia into neural stem cells for regeneration.
Original languageEnglish
Article numbere58756
Number of pages32
Early online date2 Feb 2021
Publication statusPublished - 12 Feb 2021

Bibliographical note


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

MSCA (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.


We thank our labs and C Rezaval for discussions and comments on the manuscript; S Corneliussen, T Schunke, and S Dietz for technical help; Y Fan, A Gould, Y Jan, J Skeath, F Schnorrer, and H Wang for reagents; A Di Maio and Birmingham Advanced Light Microscopy for assistance; Bloomington Drosophila Stock Centre for fruit-flies and Developmental Studies Hybridoma Bank, Iowa for antibodies.

© 2021, Harrison et al.


  • Drosophila
  • Glia
  • regeneration
  • neural stem cell
  • insulin
  • IA-2
  • CNS injury


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