# Duox-driven ROS release by glia promotes regeneration in the adult Drosophila brain

## TL;DR

Glia in the fruit fly brain release ROS after injury, which helps promote brain repair and cell regeneration.

## Contribution

The study reveals a novel beneficial role of glia-derived ROS in promoting brain regeneration in adult Drosophila.

## Key findings

- Localized brain damage triggers oxidative stress and protective programs in Drosophila.
- ROS generated by glial Duox is essential for injury-induced proliferation and regeneration.
- ROS sustain pro-regenerative JNK signaling activity required for cell division.

## Abstract

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 study 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 in glial cells is responsible for injury-induced oxidative stress. Both genetic and chemical suppression of ROS in injured brains impairs regeneration. In particular, selective knockdown of calcium-sensitive Duox in glia, which show elevated calcium after injury, 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.

Brain injury in Drosophila activates Duox in glial cells, leading to ROS release, which stimulates proliferation and pro-regenerative JNK signaling in cells adjacent to the injury site, revealing a beneficial role for glia-derived ROS in promoting brain repair.

Brain injury activates calcium-dependent Duox in glial cells in Drosophila.Duox-generated ROS promote proliferation.ROS induce and prolong the activity of the JNK pathway that is required for regeneration.

Brain injury activates calcium-dependent Duox in glial cells in Drosophila.

Duox-generated ROS promote proliferation.

ROS induce and prolong the activity of the JNK pathway that is required for regeneration.

Brain injury in Drosophila activates Duox in glial cells, leading to ROS release, which stimulates proliferation and pro-regenerative JNK signaling in cells adjacent to the injury site, revealing a beneficial role for glia-derived ROS in promoting brain repair.