PhD Scientific Days 2023

Neurosciences II.

Modelling Central Nervous Injury and Regeneration using Drosophila Melanogaster

Text of the abstract

The human central nervous system (CNS, ie spinal cord and brain) does not regenerate upon injury or disease, but many animals can regenerate their nervous systems. Injury induces regenerative responses in glial cells across animals, leading to some repair and limited functional recovery. Glial regenerative responses include decreasing lesion size over time, cell debris clearance, regeneration of glial cells and induction of neural stem cells. Remarkably, animals that can regenerate their CNS do so via injury-induced neurogenesis and not from canonical neural stem cells, but frequently from glial cells. In our lab, we had previously reported that crush injury in larvae induced neural stem cell marker expression in glia. This neurogenic response involved the NG2 homologue kon-tiki and insulin signalling. However, larvae pupate, preventing the study of regenerative neurogenesis whether it could result in functional, behavioural recovery, over time. The molecular mechanisms of regenerative neurogenesis remain largely unknown. 
     My project aims to discover molecular mechanisms of injury-induced neurogenesis in adult fruit-flies. To investigate this and test whether normal behaviour can be restored after injury, a crush injury method was previously established in adult Drosophila by Losada-Perez et al (2021, Disease Models & Mechanisms), a previous post-doc in our lab. Building on this, I have improved the method to be able to identify, track and record over time individual flies. I have colour-marked each individual fly after injury to link behaviour with the cellular progression of the lesion over time.  Fly-survival was quantified over time and fly locomotion filmed by quantifying phenotypes manually and using FlyTracker. Overall, 50% of the flies survived injury by day 1 and 14% by day 7. Remarkably, locomotion of some flies improved over time. I am currently analysing how cell biology relates to locomotion recovery. This method will next enable us to discover and test molecular mechanisms of CNS regeneration in Drosophila. Thank you to MIBTP BBSRC for my funding.