Harrison, NealeConnolly, ElizabethGascón Gunieda, AliciaYang, ZidanAltenhein, BenjaminLosada Pérez, María De La PalomaMoreira, MartaSun, JunHidalgo, Alicia2024-06-262024-06-262021-02-02Harrison, N. J., Connolly, E., Gascón Gubieda, A., Yang, Z., Altenhein, B., Losada Perez, M., Moreira, M., Sun, J., & Hidalgo, A. (2021). Regenerative neurogenic response from glia requires insulin-driven neuron-glia communication. eLife, 10, e58756. https://doi.org/10.7554/eLife.5875610.7554/eLife.58756https://hdl.handle.net/20.500.14352/105285Understanding 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.engAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/journal article2050-084Xhttps://doi.org/10.7554/elife.58756open access612.8D. melanogasterDrosophilaNG2Developmental biologyDilp6Glial cellIa-2InjuryKonNeurogenesisRegenerationRegenerative medicineStem cellsNeurociencias (Biológicas)2490 Neurociencias