Dynamic changes in neuronal and glial GAL4 driver expression duringDrosophilaageing

Abstract

AbstractUnderstanding how diverse cell types come together to form a functioning brain relies on the ability to specifically target these cells. This is often done using genetic tools such as the GAL4/UAS system inDrosophila melanogaster. Surprisingly, despite its extensive usage during studies of the ageing brain, detailed spatio-temporal characterisation of GAL4 driver lines in adult flies has been lacking. Here we show that three commonly used neuronal drivers (elav[C155]-GAL4,nSyb[R57C10]-GAL4andChAT-GAL4) and the commonly used glial driverrepo-GAL4all show rapid and pronounced decreases in activity over the first 1.5 weeks of adult life, with activity becoming undetectable in some regions after 30 days. In addition to an overall decrease in GAL4 activity over time, we found notable differences in spatial patterns, mostly occurring soon after eclosion. Although all lines showed these changes, thenSyb-GAL4line exhibited the most consistent and stable expression patterns over ageing. Our findings suggest that gene transcription of key loci decreases in the aged brain, a finding broadly similar to previous work in mammalian brains. Our results also raise questions over past work on long-term expression of disease models in the brain, and stress the need to find better genetic tools for ageing studies.