Differential neuronal survival defines a novel axis of sexual dimorphism in the Drosophila brain.
Allen AM., Neville MC., Nojima T., Alejevski F., Goodwin SF.
Sex differences in behaviors arise from variations in female and male nervous systems, yet the cellular and molecular bases of these differences remain poorly defined. Here, we employ an unbiased, single-cell transcriptomic approach to investigate how sex influences the adult Drosophila melanogaster brain. We demonstrate that sex differences do not result from large-scale transcriptional reprogramming, but rather from selective modifications within shared developmental lineages mediated by the sex-differentiating transcription factors Doublesex and Fruitless. We reveal, with unprecedented resolution, the extraordinary genetic diversity within these sexually dimorphic cell types and find that birth order represents a novel axis of sexual differentiation. Neuronal identity in the adult reflects spatiotemporal patterning and sex-specific survival, with female-biased neurons emerging early and male-biased neurons arising later. This pattern reframes dimorphic neurons as "paralogous" rather than "orthologous," suggesting sex leverages distinct developmental windows to build behavioral circuits, and highlights a role for exaptation in diversifying the brain.