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

Research output: Contribution to journalArticlepeer-review

Authors

  • Elizabeth Connolly
  • Alicia Gascón Gubieda
  • Zidan Yang
  • Benjamin Altenhein
  • Maria Losada-Perez
  • Marta Moreira

Colleges, School and Institutes

Abstract

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.

Bibliographic note

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 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. Acknowledgements 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.

Details

Original languageEnglish
Article numbere58756
Number of pages32
JournaleLife
Volume10
Early online date2 Feb 2021
Publication statusPublished - 12 Feb 2021

Keywords

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