Sexually-dimorphic neurons in the Drosophila whole-brain connectome

Deutsch, D.; Matsliah, A.; Wang, K.; Dorkenwald, S.; Mondal, A.; Burke, A.; Hebditch, J.; Gager, J.; Yu, S.-C.; Sterling, A.; MkKellar, C.; Schlegel, P.; Gerhard, S.; Sterne, G.; Costa, M.; Eichler, K.; Yin, Y.; Jefferis, G. S. X. E.; Seung, H. S.; Murthy, M.

doi:10.1101/2025.06.10.658788

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bioRxiv · 10.1101/2025.06.10.658788

Sexually-dimorphic neurons in the Drosophila whole-brain connectome

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Abstract

Sexual dimorphisms in the brain arise from differences in cell number, morphology, and connectivity, and underlie sex-specific behaviors. In Drosophila, these differences are largely governed by the transcription factors Fruitless (Fru) and Doublesex (Dsx), expressed in neurons implicated in reproductive and social behaviors. However, how these neurons are integrated into the connectome to drive different behaviors in different sexes remains unclear. Here, we identify 98 putative Fru- or Dsx-expressing cell types ([~]1700 neurons) in the female whole-brain connectome by matching electron microscopy reconstructions to light microscopy images. We then analyze their connectivity within the whole-brain network. Fru/Dsx neurons are strongly interconnected, but are not part of a private network. We measure distances to the sensory periphery to examine multisensory interactions, and map connections to descending neurons that drive behavior. We further cluster Fru/Dsx neurons based on whole-brain connectivity, and uncover functional groupings. We analyze a subset of strongly connected Fru/Dsx neurons to make functional predictions, and test some of these with experiments. Together, this work provides a brain-wide framework for understanding the organization of sexually dimorphic circuits and establishes a resource for dissecting the neural basis of social and sexual behaviors.

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Deutsch, D., Matsliah, A., Wang, K., Dorkenwald, S., Mondal, A., Burke, A., Hebditch, J., Gager, J., Yu, S.-C., Sterling, A., MkKellar, C., Schlegel, P., Gerhard, S., Sterne, G., Costa, M., Eichler, K., Yin, Y., Jefferis, G. S. X. E., Seung, H. S., Murthy, M.. 2025-06-14. Sexually-dimorphic neurons in the Drosophila whole-brain connectome. https://doi.org/10.1101/2025.06.10.658788

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