ABSTRACT
A key goal to promote central nervous system regeneration is to discover mechanisms of injury-induced de novo neurogenesis. Glial cells might induce neurogenesis upon injury, but this is debated, and underlying mechanisms are unknown. A critical missing link is the identification of neuronal factors that could interact with glial NG2 to facilitate regeneration. Here, we used Drosophila genetics to search for neuronal partners of the NG2 homologue Kon-tiki (Kon), and identified Ia-2, involved in insulin secretion. Ia-2 is exclusively neuronal, and alterations in Ia-2 function destabilized cell fate. Injury increased ia-2 expression and induced neural stem cells. Using glial markers, genetic epistasis analysis and lineage tracing, we demonstrate that Ia-2 functions together with Kon and Dilp6 to induce de novo neural stem cells from glia. Altogether, Ia-2 and Kon initiate a neuron-glia interaction loop that coordinates de novo production of both neurons and glia for central nervous system regeneration.
