TY - JOUR TI - Regenerative neurogenic response from glia requires insulin-driven neuron-glia communication AU - Harrison, Neale J AU - Connolly, Elizabeth AU - Gascón Gubieda, Alicia AU - Yang, Zidan AU - Altenhein, Benjamin AU - Losada Perez, Maria AU - Moreira, Marta AU - Sun, Jun AU - Hidalgo, Alicia A2 - Bellen, Hugo J A2 - Banerjee, Utpal A2 - Wang, Hongyan VL - 10 PY - 2021 DA - 2021/02/02 SP - e58756 C1 - eLife 2021;10:e58756 DO - 10.7554/eLife.58756 UR - https://doi.org/10.7554/eLife.58756 AB - 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. KW - Drosophila KW - glial cell KW - dilp6 KW - ia-2 KW - regeneration KW - neurogenesis KW - kon KW - NG2 KW - injury JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -