Biology subjects

Dzitoyeva, S.

Publications and source records attributed to Dzitoyeva, S..

5 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

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

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↗

bioRxiv2019

Egg activation triggers clearance of maternally deposited RNA binding proteins

The maternal-to-zygotic transition (MZT) is a conserved step in animal development, where control is passed from the maternal genome to the zygotic one. Although the MZT is typically considered from its impact on the transcriptome, we previously found that three maternally deposited Drosophila RNA binding proteins (ME31B, Trailer Hitch [TRAL], and Cup) are also cleared during the MZT by unknown mechanisms. Here, we show that these proteins are degraded by the ubiquitin-proteasome system. Kondo, an E2 conjugating enzyme, and the E3 CTLH ligase are required for the destruction of ME31B, TRAL, and Cup. Importantly, despite occurring hours earlier, egg activation establishes the timer for clearance of these proteins by activating the Pan Gu kinase, which in turn stimulates translation of Kondo mRNA. In other words, egg activation triggers a series of regulatory events that culminate in the degradation of maternally deposited RNA binding proteins several hours later. Clearance of the maternal protein dowry thus appears to be a coordinated, but as-yet underappreciated, aspect of the MZT.\n\nHIGHLIGHTSO_LIDegradation of ME31B requires the PNG kinase, but not fertilization\nC_LIO_LIThe ubiquitin-proteasome system degrades ME31B via CTLH E3 ligase and the UBC-E2H/Kondo ubiquitin-conjugating enzyme\nC_LIO_LIThe association of ME31B with the CTLH complex does not require PNG activity\nC_LIO_LIPNG kinase mediates the translational upregulation of Kondo at egg activation\nC_LI

developmental biology↗