Structural plasticity and regeneration in the Drosophila brain.

The project aims to discover the molecular mechanisms of regenerative neurogenesis. The central nervous system (CNS) does not regenerate upon injury or disease in humans. However, some animals can regenerate and they do so by inducing de novo neurogenesis. Most often, regenerative neurogenesis is induced from cells that are distinct from developmental neuroblasts. We have recently discovered that CNS injury in Drosophila induces an ectopic neural stem cell marker in glia (Harrison et al 2021 eLife). We will test the hypothesis that signals produced in injury may activate natural in vivo reprogramming of glial cells into neural stem cells, conducive to regeneration. We will test this using the fruit-fly Drosophila as a model organism. We have identified candidate genes that could regulate these events. We will: 1) Establish an injury protocol in the adult fruit-fly in which to test regeneration, at a cellular level and also recovery of behaviour. 2) Test a set of candidate genes for their ability to in vivo reprogram glia into neural stem cells upon genetic manipulation. 3) Test whether genetic manipulation results in neural circuit integration and recovery of behaviour.