Sproston CJ, Rak JE, Marin EC, Kondo S, Williams DW (2025)
Hemilineage-specific deployment of the pro-apoptotic RHG genes reaper and grim during neurogenesis sculpts segment and sex-specific neural network composition in Drosophila.Development
During development, populations of neuronal stem cells generate neurons in a modular fashion to produce a striking diversity of subtypes. Within the Drosophila central nervous system, a stereotyped, segmentally repeated array of stem cells, called neuroblasts, generate identifiable lineages of neurons, each comprising two hemilineages. Here, we show that a key part of early fate determination within a hemilineage is selective neuronal cell death. This precise deletion of neurons occurs throughout the nervous system, removing neurons of every transmitter type in a segment-specific fashion. Using hybridisation chain reaction in situ (HCR) we reveal the proapoptotic RHG genes reaper and grim, but not hid, are transcribed within doomed neurons. Novel T2A-GAL4 knock-in reporters for reaper and grim reveal complex but repeatable expression patterns within hemilineages. These data support functional analysis with null mutants showing that reaper and grim play a complex role in sculpting lineage populations. We show that segmental and sex-specific differences in neuronal subtypes is mediated by a temporal switching to death within identified hemilineages during neurogenesis to shape adult networks.