Duox-driven ROS release by glia promote regeneration in the adult Drosophila brain
Tissue damage activates immediate responses to restrict further harm and initiate repair. How injury sensing is coupled to regeneration is still not well understood. Here, we studied regenerative responses in the adult Drosophila brain, where proliferation is normally strongly restricted.  We show that localized brain damage triggers oxidative stress and diverse brain protective programs. We find that ROS generation by the NADPH Oxidase Duox on glial cells is responsible for injury-induced oxidative stress. Both genetic and chemical suppression of ROS in injured brains lead to impaired regeneration. In particular, selective knock-down of calcium-sensitive duox in glia, which show elevated calcium after injury, strongly reduces injury-induced proliferation. We further provide evidence that diffusing ROS can sustain the activity of pro-regenerative signaling, which is required to stimulate cell divisions. Although oxidative stress is generally considered as harmful in the brain, we uncover here an unanticipated beneficial role of transient ROS release by glia to promote brain repair. Overall design: RNAseq profiling of glial cells from optic lobes of adult fly brains in a intact condition (non-injured, NI) and 48 hours after an injured condition (injured, INJ).