Channel nuclear pore protein 54 directs sexual differentiation and neuronal wiring required for female reproductive behaviors inDrosophila

Abstract

The post-mating response induced by male-derived sex-peptide in Drosophila females is a wellestablished model to elucidate how complex innate behaviors are hard-wired into the brain. Here, we found that the channel nuclear pore protein Nup54 is essential for the sex-peptide response as viable mutant alleles do not lay eggs and reduce receptivity upon sex-peptide exposure. Nup54 directs correct wiring of few adult brain neurons that express pickpocket and are required for egg laying, but channel Nups also mediate sexual differentiation and male X-chromosome dosage compensation. Consistent with links of Nups to speciation, the Nup54 promoter is a hot spot for rapid evolution and Nup54 is differentially expressed in the brain. These results implicate altered expression of Nup54 to the onset of speciation processes leading to changes in neuronal wiring and sexual differentiation as a response to sexual conflict arising from male-derived SP to direct the female post-mating response.

Rapid evolution of promoters from germline-specifically expressed genes including transposon silencing factors

“…Since establishing transposon resistance involves forced selection, genes whose expression changes result in pleiotropic effect, like channel Nup54, could combine adaptations in piRNA processing with changes in neuronal wiring resulting in altered behavioural preferences (19). Of note, in D. simulans, a very close relative of D. melanogaster projections of fruitless P1 sensory neurons that control courtship have changed and alter mate preference (49).…”

“…Transposon mobility has been attributed to the accumulation of sequence changes in promoter regions because of the presence of open chromatin around the transcription start site of genes (42). Interestingly, in core NPC genes, rapid evolution mostly led to accumulation of indels (19,20), while piRNA genes display equal accumulation of indels and base changes.…”

“…Since Nups have been shown to function in transposon silencing in the germline (12 from 14 tested are above the control) and display fast evolving promoters (15,19,20), we analysed the rate of evolution in promoters and coding regions of piRNA pathway genes. We separated all piRNA genes based on their genetic requirement into two categories: piRNA factors essential in somatic cells, including the soma-specific piRNA factor Yb and piRNA factors expressed in both somatic and germline cells (cTGS and piRNA biogenesis, Fig.…”

“…Interestingly, in Drosophila, Nups were shown to affect transposon silencing in both the germline (15,17), and in somatic cells of the ovary, here specifically by contributing to the conversion of precursor RNAs from the flam locus into piRNAs (18). Recently, we found that inner and outer ring Nups in the nuclear pore complex (NPC) evolve rapidly through indel accumulation in their promoters (19,20). Such promoter indel variability in Nup54 has dominant, pleiotropic effects on sexual differentiation including neuronal wiring important for female post-mating behaviours directed by male-derived sex peptide, that as a result of sexual conflict could drive speciation by such mechanism (16,19,21).…”

“…Recently, we found that inner and outer ring Nups in the nuclear pore complex (NPC) evolve rapidly through indel accumulation in their promoters (19,20). Such promoter indel variability in Nup54 has dominant, pleiotropic effects on sexual differentiation including neuronal wiring important for female post-mating behaviours directed by male-derived sex peptide, that as a result of sexual conflict could drive speciation by such mechanism (16,19,21). Intriguingly, nuclear import/export pathways have been linked to speciation through hybrid incompatibility, but are in addition important for many cellular processes beyond piRNA processing (22,23).…”