Biology subjects

Ryvkin, J.

Publications and source records attributed to Ryvkin, J..

4 recordsLinked to original sources

bioRxiv2025

Cell-type-resolved RNA-seq reveals molecular engrams of sexual experience in Drosophila neuromodulatory neurons.

Flexible behavioral responses rely on the ability of neural circuits to adapt their physiology and output to changing social and environmental contexts. Neuromodulation plays a central role in this flexibility, dynamically tuning neuronal activity and gene expression to align behavior with experience and internal states. Yet how specific experiences and motivational conditions are encoded within neuromodulatory neurons remains underexplored. Here, we show that distinct motivational outcomes drive discrete, largely non-overlapping transcriptional programs across three neuromodulatory neuronal populations in male Drosophila brains. Using cell-type-resolved RNA sequencing, we profiled the transcriptomes of serotonergic (Trh), octopaminergic/tyraminergic (Tdc2), and neuropeptide F receptor (NPFR) neurons under three conditions: successful mating, sexual rejection, and the absence of social or sexual interaction. Each experience induced a unique "molecular engram" within specific neuron types. NPFR neurons exhibited the strongest transcriptional remodeling following rejection, Tdc2 neurons preferentially represented the naive-single state, and Trh neurons displayed balanced, experience-specific tuning. Shared differentially expressed genes across neuronal classes were few and often were oppositely regulated, revealing divergent circuit-specific logic. Experience triggered multilayered reprogramming across chromatin organization, RNA metabolism, translation, proteostasis and synaptic machinery, with selective recalibration of vesicle trafficking, and neuroplasticity. We further identified a compact, cross-circuit "rejection core" enriched for circadian, stress, metabolic, neuropeptidergic, and synaptic components. Together, these findings demonstrate how neuromodulatory circuits translate social experience into coordinated molecular and synaptic adaptations that enable behavioral flexibility.

neuroscience↗

bioRxiv2025

Aberrant inheritance of extrachromosomal DNA amplifications promotes cancer evolution

Gene amplification in the form of extrachromosomal DNA (ecDNA) is a frequent driver in multiple cancer types. As ecDNA lack centromeres, their mitotic segregation does not follow traditional inheritance principles. However, the mechanisms that govern ecDNA fate following mitosis remain unclear. We found that ecDNA undergo numerical and structural optimization under increased selective pressure, with mitotic chromosomal tethering, or detachment, dictating ecDNA fate. When tethered, ecDNA aggregates promote uneven distribution into the newly formed daughter cells, thereby driving inter-cellular numerical heterogeneity and rapid increase of amplification under selective pressure. Mitotically detached ecDNA frequently encapsulate within micronuclei of variable size and content that appear to be highly fragile. Strikingly, ecDNA enclosed in very small micronuclei, which we term nanonuclei, are being actively degraded through autophagy. Together with ongoing structural rearrangements, nanonuclear ecDNA degradation promotes their structural evolution, which facilitates cancer cell adaptation. Our work highlights ecDNA aggregation, micronucleation, and degradation, as pivotal events in directing cancer genome evolution trajectories.

cancer biology↗

bioRxiv2022

Sexual deprivation induces a CRF independent stress response and decreases resistance to stressors in Drosophila via a subpopulation of Neuropeptide F receptor-expressing neurons

Living in a changing environment composed of other behaving animals entails both opportunities and challenges to obtain resources and mating partners. Actions that promote survival and reproduction are reinforced by the brain reward systems, whereas coping with the challenges associated with obtaining these rewards are mediated by stress response pathways. The activation of the latter can impair health and shorten lifespan. Although similar responses to social opportunity and challenge exist across the animal kingdom, little is known about the mechanisms that process reward and stress under different social conditions. Here, we studied the interplay between deprivation of sexual reward and stress response in Drosophila melanogaster and discovered that repeated failures to obtain sexual reward induces a frustration-like state that is characterized by increased arousal, persistent sexual motivation, and impaired ability to cope with starvation and oxidative stressors. We show that this increased arousal and sensitivity to starvation is mediated by disinhibition of neurons that express receptors for the fly homologue of neuropeptide Y (neuropeptide F, NPF). We furthermore demonstrate the existence of an anatomical overlap between stress and reward systems in the fly brain in the form of neurons that co-express receptors for NPF (NPFR) and the corticotropin-releasing factor (CRF)-like homologue Diuretic hormone 44 (Dh44), and that deprivation of sexual reward leads to translocation of forkhead box-subgroup O (FoxO) to the cytoplasm in these neurons. Nevertheless, the activity of Dh44 neurons alone does not mediate sensitivity to starvation and aroused behavior following sexual deprivation, instead, these responses are mediated by disinhibition of ~12-16 NPFR-expressing neurons via a dynamin-independent synaptic signaling mechanism, suggesting the existence of a NPFR mediated stress pathway which is Dh44-independent. This paves the path for using simple model organisms to dissect mechanisms behind anticipation of reward, and more specifically, to determine what happens when expectations to obtain natural and drug rewards are not met.

animal behavior and cognition↗

bioRxiv2020

Transcriptome Analysis of NPFR Neurons Reveals a Connection Between proteome Diversity and Social Behavior

Complex social behaviors are mediated by the activity of highly intricate neuronal networks, the function of which is shaped by their transcriptomic and proteomic content. Contemporary advances in neurogenetics, genomics, and tools for automated behavior analysis make it possible to functionally connect the transcriptome profile of candidate neurons to their role in regulating behavior. In this study we used Drosophila melanogaster to explore the molecular signature of neurons expressing receptor for neuropeptide F (NPF), the fly homologue of neuropeptide Y (NPY). By comparing the transcription profile of NPFR neurons to those of nine other populations of neurons, we discovered that NPFR neurons exhibit a unique transcriptome, enriched with receptors for various neuropeptides and neuromodulators, as well as with genes known to regulate behavioral processes, such as learning and memory. By manipulating RNA editing and protein ubiquitination programs specifically in NPFR neurons, we demonstrate that their delicate transcriptome and proteome repertoires are required to suppress male courtship and certain features of social group interaction. Our results highlight the importance of transcriptome and proteome diversity in the regulation of complex behaviors and pave the path for future dissection of the spatiotemporal regulation of genes within highly complex tissues, such as the brain.

neuroscience↗