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

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 <i>Drosophila</i> to search for genes functionally related to the <i>NG2</i> homologue <i>kon-tiki (kon),</i> and identified <i>Islet Antigen-2 (Ia-2),</i> required in neurons for insulin secretion. Both loss and over-expression of <i>ia-2</i> induced neural stem cell gene expression, injury increased <i>ia-2</i> expression and induced ectopic neural stem cells. Using genetic analysis and lineage tracing, we demonstrate that Ia-2 and Kon regulate <i>Drosophila</i> 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.