Biology subjects

Okuwa, S.

Publications and source records attributed to Okuwa, S..

3 recordsLinked to original sources

bioRxiv2025

Pheromone circuits and transcriptional cascades modulating transcriptional and chromatin states in the Drosophila central brain with social experience

Social experience significantly influences the behavioral and physiological responses of animals, including humans. In many animals, social isolation increases aggression, courtship, locomotion, and feeding while disrupting sleep. This occurs when peripheral neurons detect social signals, such as pheromones, which activate decision-making circuits in the brain. However, the molecular and circuit mechanisms of how chronic social isolation or enrichment alter gene expression and affect neuronal function and behavior remain unclear. In this study, we examined how transcription patterns and chromatin marks in male Drosophila brains change in response to social experience, and the effect of pheromone circuits and transcription factors involved in social circuit function. We focused on pheromone receptors Or47b and Or67d, as well as transcription factors FruM and DsxM. Our findings suggest that social experience affects multiple genes in the central brain. Disrupting Or47b, Or67d, FruM, and DsxM function moderated the transcriptional responses through antagonistic interactions. Specifically, Or47b circuits predominantly mediated transcriptional responses to social isolation through DsxM function, while Or67d and FruM regulated responses to group housing. Notably, mutants of fruM and dsxM exhibited more extensive transcriptional changes in the brain than Or mutants, especially for FruM/DsxM target genes. While social experience did not lead to detectable alterations in the overall chromatin profile in the whole brain, mutants of the four genes resulted in significant changes in the enrichment of H3K4me3 and RNA polymerase II (RNAPolII) compared to wild type. Furthermore, mutants in fruM and dsxM generally eliminated social experience-dependent changes in sleep and locomotion behaviors, whereas Or mutants exhibited more modest disruptions. Overall, our results uncover the pheromone circuits and transcriptional cascades in regulating molecular and behavioral responses to social experience.

neuroscience↗

bioRxiv2025

Social experience alters behaviors by reprogramming the Fruitless pathway and circadian state in Drosophila

From flies to humans, social experience affects various cognitive and behavioral processes. Previous studies have shown that group housing suppresses many behaviors like courtship, aggression, and feeding in Drosophila melanogaster, in addition to resetting the circadian state. Here, we focus on group housing-induced courtship suppression. To determine the mechanisms by which social experience modulates courtship behaviors, we performed bulk tissue RNAseq and single-cell RNAseq from cells expressing FruitlessM (FruM) and DoublesexM (DsxM), two transcription factors that label interconnected neural circuits for socially driven behaviors, from grouped or isolated male brains. These revealed that social isolation alters fru and dsx levels throughout the brain. Knocking down fruM in different fruM-positive neuron subpopulations in the brains has diverse effects on social experience-dependent changes in courtship. Furthermore, group housing increases the expression of stripe (sr) and Hormone receptor-like in 38 (Hr38) genes encoding neural activity-induced transcription factors in most neurons within social circuits. We found that knocking down sr in fruM-positive neurons effectively eliminates the impact of social experience by increasing courtship in group-housed males. Importantly, social experience also alters the expression of FruM/DsxM putative target genes regulating circadian states throughout the brain. Disrupting the function of multiple circadian genes diminishes the effect of group housing on courtship. Our findings suggest that group housing/social enrichment suppresses courtship by reprogramming the circadian arousal state, whereas courtship-elevating effects of social experience rely on unique influences of FruM expression and function in different neurons within social and clock circuits. These results are significant as they point to modulation of circadian arousal state as a possible central strategy for mediating the pleiotropic effects of social experience on organismal responses.

neuroscience↗

bioRxiv2025

Deciphering the combinatorial expression pattern and genetic regulatory mechanisms of Beats and Sides in the olfactory circuits of Drosophila

Over the past decades, many critical molecular players have been uncovered to control distinct steps in olfactory circuit assembly in Drosophila. Among these, multi-member gene families of cell surface proteins are of interest because they can act as neuron-specific identification/recognition tags in combinations and contribute to circuit assembly in complex brains through their heterophilic or homophilic interactions. Recently, a multi-protein interactome has been described between the Beat and Side families of IgSF proteins. Here, we use the publicly available single-cell RNA-seq datasets and newly generated gene trap transgenic driver lines to probe the in vivo spatial expression pattern of the beat/side gene families in odorant receptor neurons (ORNs) and their synaptic target projection neurons (PNs). Our results revealed that each ORN and its synaptic target PN class expresses a class-specific combination of beat/side genes, hierarchically regulated by lineage-specific genetic programs. Though ORNs or PNs from closer lineages tend to possess more similar beat/side profiles, we also found many examples of divergence from this pattern among closely related ORNs and closely related PNs. To explore whether the class-specific combination of beats/sides defines ORN-PN matching specificity, we perturbed presynaptic beat-IIa and postsynaptic side-IV in two ORN-PN partners. However, disruption of Beat-IIa-Side-IV interaction did not produce any significant mistargeting in these two examined glomeruli. Though without affecting general glomerular targeting, knockdown of side in ORNs leads to the reduction of synaptic development. Interestingly, we found conserved expression patterns of beat/side orthologs across ORNs in ants and mosquitoes, indicating the shared regulatory strategies specifying the expression of these duplicated paralogs in insect evolution. Overall, this comprehensive analysis of expression patterns lays a foundation for in-depth functional investigations into how Beat/Side combinatorial expression contributes to the olfactory circuit assembly.

neuroscience↗