16/10/25
During nervous system development an extraordinary diversity of neurons must be generated in the right place, at the right time, with the correct ratios. Within the insect ventral nerve cord (VNC), the analogue of the spinal cord, discrete populations of stem cells generate neuronal lineages that ‘wire together’ to form the networks essential for controlling walking and flying.
Previous work from the Williams lab (Pop et al., 2020) demonstrated that in the Fruit Fly (Drosophila melanogaster), a specific type of early neurogenic programmed cell death (PCD) sculpts the outputs of these lineages to selectively remove specific types of neurons as they are being born. Differences in the presence of specific types of neurons between different segments of the VNC and sexes underpins the generation of circuits important for behaviours such as mating song generation in male flies but not females.
In this new study, published in Development, Connor Sproston and colleagues in the Williams Lab show that lineage-specific levels of 2 pro-apoptotic genes, grim and reaper, regulate neurogenic PCD within the developing VNC, with specific populations of cells doomed to die expressing distinct combination of grimand/or reaper. Loss of function analysis demonstrates that specific populations have distinctly different requirements for the expression of these pro-apoptotic genes, suggesting that distinct regulatory mechanisms regulate the expression of these genes within each lineage population.
Focusing on segment and sex-specific PCD, Sproston et al., identified a specific lineage population which ‘turns on’ death late during neurogenesis to selectively remove a subset of male-specific neurons in females, which are known to regulate the mating song in males. Using mutant analysis, precise genetic manipulations and quantitative analysis of gene transcription in this population, they show that the expression of the female differentiation factor transformer regulates reaper expression in order to instruct the removal of these neurons.
This study paves the way for a deeper understanding of how diverse neuronal circuit motifs can be generated and opens avenues for exploring the ways in which sex and species-specific differences in the nervous system may emerge.
For further information on this story or about the Centre please contact the Research Strategy Manager, Centre for Developmental Neurobiology, King’s College London.
The Centre for Developmental Neurobiology is part of the Institute of Psychiatry, Psychology & Neuroscience at King's College London.
