Regeneration in the adultDrosophilabrain

Abstract

Understanding the molecular and cellular mechanisms underlying neurogenesis after injury is crucial for developing tools for brain repair. We have established an adult Drosophila melanogaster model for investigating regeneration after central brain injury. Within 24 hours after Penetrating Traumatic Brain Injury (PTBI) to the central brain, we observe a significant increase in the number of proliferating cells. Between one- and two-weeks post-injury, we detect the generation of new neurons and glia and the formation of new axon tracts that target appropriate brain regions, suggesting there could be functional regeneration. Consistent with functional regeneration, locomotion abnormalities observed shortly after PTBI are largely reversed within 2 weeks of injury. Further, we find that cells surrounding the injury site upregulate neuroblast genes, such as asense and deadpan, and demonstrate that these cells give rise to the new neurons and glia. Taken together, our data support the hypothesis that young, adult Drosophila brains are capable of neuronal repair after central brain injury. We anticipate that our model will facilitate the dissection of the mechanisms of neural regeneration and anticipate that these processes will have relevance to humans.

Polyploidy in the adult Drosophila brain

“…We stained for G2 and mitotic cell cycle markers (phospho-histone H3 and Cyclin A) in over 100 adult brains at different ages and never observed a convincing G2 or mitotic event. However, we may have missed rare, transient cell cycle events that are captured by permanent lineage tracing approaches ( Crocker et al, 2020 ; Fernández-Hernández et al, 2013 ). Both our cell number counts and cell death measurements indicate a steady decline in cell number in the adult brain with age ( Figure 6—figure supplement 1 ), and suggest that under normal ageing conditions mitoses are likely rare.…”

“…A population of about 40 adult neural progenitors has been reported in the optic lobe and a population of glial progenitors has been reported in the central brain ( Fernández-Hernández et al, 2013 ; Foo et al, 2017 ). Upon damage or cell loss, hallmarks of cycling have been shown to be activated, although the overall level of proliferation in the adult brain remains very low ( Crocker et al, 2020 ; Fernandez-Hernandez et al, 2019 ; Fernández-Hernández et al, 2013 ; Foo et al, 2017 ; Li et al, 2020 ). Thus, the brain of the adult fly is thought to be almost entirely postmitotic with most cells in G0 with a diploid (2C) DNA content.…”