Biology subjects

Ruvinsky, I.

Publications and source records attributed to Ruvinsky, I..

8 recordsLinked to original sources

bioRxiv2024

The roles of TGFβ and serotonin signaling in regulating proliferation of oocyte precursors and germline aging

AO_SCPLOWBSTRACTC_SCPLOWThe decline of oocyte quality in aging but otherwise relatively healthy individuals compels a search for underlying mechanisms. Building upon a finding that exposure to male pheromone ascr#10 improves oocyte quality in C. elegans, we uncovered a regulatory cascade that promotes proliferation of oocyte precursors in adults and regulates oocyte quality. We found that the male pheromone promotes proliferation of oocyte precursors by upregulating LAG-2, a ligand of the Notch-like pathway in the germline stem cell niche. LAG-2 is upregulated by a TGF{beta}-like ligand DAF-7 revealing similarity of regulatory mechanisms that promote germline proliferation in adults and larvae. A serotonin circuit that also regulates food search and consumption upregulates DAF-7 specifically in adults. The serotonin/DAF-7 signaling promotes germline expansion to compensate for oocyte expenditure which is increased by the male pheromone. Finally, we show that the earliest events in reproductive aging may be due to declining expression of LAG-2 and DAF-7. Our findings highlight neuronal signals that promote germline proliferation in response to the environment and argue that deteriorating oocyte quality may be due to reduced neuronal expression of key germline regulators.

developmental biology↗

bioRxiv2023

Periods of environmental sensitivity couple larval behavior and development

SO_SCPLOWUMMARYC_SCPLOWThe typical life cycle in most animal phyla includes a larval period that bridges embryogenesis and adulthood1. Despite the great diversity of larval forms, all larvae grow, acquire adult morphology and function, while navigating their habitats to obtain resources necessary for development. How larval development is coordinated with behavior remains substantially unclear. Here, we describe features of the iterative organization of larval stages that serve to assess the environment and procure resources prior to costly developmental commitments. We found that male-excreted pheromones accelerate2-4 the onset of adulthood in C. elegans hermaphrodites by coordinately advancing multiple developmental events and growth during the last larval stage. The larvae are sensitive to the accelerating male pheromones only at the end of the penultimate larval stage, just before the acceleration begins. Other larval stages also contain windows of sensitivity to environmental inputs. Importantly, behaviors associated with search and consumption of food are distinct between early and late portions of larval stages. We infer that each larval stage in C. elegans is subdivided into two epochs: A) global assessment of the environment to identify the most suitable patch and B) consumption of sufficient food and acquisition of salient information for developmental events in the next stage. We predict that in larvae of other species behavior is also divided into distinct epochs optimized either for assessing the habitat or obtaining the resources. Thus, a major role of larval behavior is to coordinate the orderly progression of development in variable environments. "Life is what happens to you when youre busy making other plans." Allen Saunders (popularized by John Lennon)

developmental biology↗

bioRxiv2023

Scaling, correlations, and artifacts in biological timeseries

SO_SCPLOWUMMARYC_SCPLOWTime is a key variable in biology. Conceptual and methodological advances focused recent studies of timing in biological systems on monitoring trait dynamics in singled individuals. Here we contribute to this effort by analyzing general properties of individual timeseries. We make four broad claims. First, we show that for traits that range from behavior in animals, to growth in plants, to division timing in cell lineages, faster timeseries tend to be comprised of consistently shorter sub-stages, not a few unusually fast sub-stages. We demonstrate that this property constitutes a particular type of scaling that can be readily detected by a straightforward comparison of absolute and relative variability within timeseries data for any trait. We show that correlations within timeseries are necessary and sufficient for the type of scaling we describe and infer that the ubiquitous occurrence of scaling results from natural correlations within the continuous processes that govern trait dynamics. Second, failing to observe scaling indicates a break in correlation and, we argue, a switch in the mechanisms underlying the rate of trait change. Third, we caution that analyses of individual timeseries are highly susceptible to batch effects, but contend that it is possible to detect signal despite the artifactual correlations introduced by batching. Finally, we show that the timing of biological process that scale is overdispersed compared to matched but uncorrelated comparisons; this is an advantage in variable environments. Our results advance understanding of common properties of biological timeseries and offer practical tools for their further study.

systems biology↗

bioRxiv2023

Serotonergic signaling plays a deeply conserved role in improving oocyte quality

AO_SCPLOWBSTRACTC_SCPLOWDeclining germline quality is a major cause of reproductive senescence. Potential remedies could be found by studying regulatory pathways that promote germline quality. Several lines of evidence, including a C. elegans male pheromone ascr#10 that counteracts the effects of germline aging in hermaphrodites, suggest that the nervous system plays an important role in regulating germline quality. Inspired by the fact that serotonin mediates ascr#10 signaling, here we show that serotonin reuptake inhibitors recapitulate the effects of ascr#10 on the germline and promote healthy oocyte aging in C. elegans. Surprisingly, we found that pharmacological increase of serotonin signaling stimulates several developmental processes in D. melanogaster, including improved oocyte quality, although underlying mechanisms appear to be different between worms and flies. Our results reveal a plausibly conserved role for serotonin in maintaining germline quality and identify a class of therapeutic interventions using available compounds that could efficiently forestall reproductive aging.

developmental biology↗

bioRxiv2023

A C. elegans male pheromone feminizes germline gene expression in hermaphrodites and imposes life-history costs

AO_SCPLOWBSTRACTC_SCPLOWSex pheromones improve reproductive success, but also impose costs. Here we show that even brief exposure to physiological amounts of the dominant C. elegans male pheromone, ascr#10, alters the expression of thousands of genes in hermaphrodites. The most dramatic effect on the transcriptome was the upregulation of genes expressed during oogenesis and downregulation of genes associated with male gametogenesis. Among the detrimental effects of ascr#10 on hermaphrodites is the increased risk of persistent infections caused by pathological pharyngeal hypertrophy. Our results reveal a way in which social signals help to resolve the inherent conflict between spermatogenesis and oogenesis in a simultaneous hermaphrodite, presumably to optimally align reproductive function to the presence of potential mating partners. They also show that the beneficial effects of the pheromone are accompanied by harmful consequences that reduce lifespan.

evolutionary biology↗

bioRxiv2022

Sex-specificity of the C. elegans metabolome

Recent studies of animal metabolism have revealed large numbers of novel metabolites that are involved in all aspects of organismal biology, but it is unclear to what extent metabolomes differ between sexes. Here, using untargeted comparative metabolomics for the analysis of wildtype animals and a series of germline mutants, we show that C. elegans hermaphrodites and males exhibit pervasive metabolomic differences. Several hundred small molecules are produced exclusively or in much larger amounts in one sex, including a host of previously unreported metabolites that incorporate building blocks from nucleoside, carbohydrate, lipid, and amino acid metabolism. A subset of male-enriched metabolites is specifically associated with the presence of a male germline, whereas enrichment of other compounds requires a male soma. Further, we show that one of the male germline-dependent metabolites, an unusual dipeptide incorporating N,N-dimethyltryptophan, accelerates the last stage of larval development in hermaphrodites. Our results serve as a foundation for mechanistic studies of how the genetic sex of soma and germline shape the C. elegans metabolome and provides a blueprint for the discovery of sex-dependent metabolites in other animals.

bioinformatics↗

bioRxiv2022

Serotonin coordinates reproductive functions in Caenorhabditis elegans

Reproduction alters animal behavior and physiology, but neuronal circuits that coordinate these changes remain largely unknown. Insights into mechanisms that regulate and possibly coordinate reproduction-related traits could be gleaned from the study of sex pheromones that manipulate potential mating partners to improve reproductive success. In C. elegans, the prominent male pheromone, ascr#10, modifies reproductive behavior and several aspects of reproductive physiology in hermaphrodite recipients, including improving oocyte quality. Here we show that a circuit that contains serotonin-producing and serotonin-uptaking neurons plays a key role in mediating these beneficial effects of ascr#10. We also demonstrate that increased serotonergic signaling promotes proliferation of germline progenitors in adult hermaphrodites. Our results establish a role for serotonin in maintaining germline quality and highlight a simple neuronal circuit that acts as a linchpin that couples food intake, mating behavior, reproductive output, and germline renewal and provisioning.

neuroscience↗

bioRxiv2020

Inferring temporal organization of postembryonic development from high-content behavioral tracking

AO_SCPLOWBSTRACTC_SCPLOWUnderstanding temporal regulation of development remains an important challenge. Whereas average, species-typical timing of many developmental processes has been established, less is known about inter-individual variability and correlations in timing of specific events. We addressed these questions in the context of postembryonic development in Caenorhabditis elegans. Based on patterns of locomotor activity of freely moving animals, we inferred durations of four larval stages (L1-L4) in over 100 individuals. Analysis of these data supports several notable conclusions. Individuals have consistently faster or slower rates of development because durations of L1 through L3 stages are positively correlated. The last larval stage, the L4, is less variable than earlier stages and its duration is largely independent of the rate of early larval development, implying existence of two distinct larval epochs. We argue that characteristic patterns of variation and correlation arise because duration of each stage tends to scale relative to total developmental time. This scaling relationship suggests that each larval stage is not limited by an absolute duration, but is instead terminated when a subset of events that must occur prior to adulthood have been completed. The approach described here offers a scalable platform that will facilitate the study of temporal regulation of postembryonic development.

developmental biology↗