Channel nuclear pore protein 54 directs sexual differentiation and neuronal wiring of female reproductive behaviors in Drosophila

Mohanakarthik Ponnadai Nallasivan, Irmgard Haussmann, Alberto Civetta, Matthias Soller

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Background: Female reproductive behaviors and physiology change profoundly after mating. The control of pregnancy-associated changes in physiology and behaviors are largely hard-wired into the brain to guarantee reproductive success, yet the gene expression programs that direct neuronal differentiation and circuit wiring at the end of the sex determination pathway in response to mating are largely unknown. In Drosophila, the post-mating response induced by male-derived sex-peptide in females is a well-established model to elucidate how complex innate behaviors are hard-wired into the brain. Here, we use a genetic approach to further characterize the molecular and cellular architecture of the sex-peptide response in Drosophila females. Results: Screening for mutations that affect the sensitivity to sex-peptide, we identified the channel nuclear pore protein Nup54 gene as an essential component for mediating the sex-peptide response, with viable mutant alleles leading to the inability of laying eggs and reducing receptivity upon sex-peptide exposure. Nup54 directs correct wiring of eight adult brain neurons that express pickpocket and are required for egg-laying, while additional channel Nups also mediate sexual differentiation. Consistent with links of Nups to speciation, the Nup54 promoter is a hot spot for rapid evolution and promoter variants alter nucleo-cytoplasmic shuttling. Conclusions: These results implicate nuclear pore functionality to neuronal wiring underlying the sex-peptide response and sexual differentiation as a response to sexual conflict arising from male-derived sex-peptide to direct the female post-mating response.

Original languageEnglish
Article number226
Number of pages7
JournalBMC Biology
Publication statusPublished - 20 Oct 2021

Bibliographical note

Funding Information:
This work was supported by the Biotechnology and Biological Science Research Council to MS and the Natural Sciences and Engineering Research Council of Canada to AC.

Publisher Copyright:
© 2021, The Author(s).


  • Nup54
  • Nuclear pore complex (NPC)
  • Sexual differentiation
  • Neuronal wiring
  • Post-mating behaviors
  • pickpocket (ppk) neurons


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