Biology subjects

Tzur, Y. B.

Publications and source records attributed to Tzur, Y. B..

4 recordsLinked to original sources

bioRxiv2025

Neuronal oversight of germline small RNAs prevents heat-induced sterility in lab-domesticated Caenorhabditis elegans

Thermal pollution, whether local or driven by global warming, threatens biodiversity in part through its detrimental effects on reproduction. Non-coding small RNAs (sRNAs) are crucial for maintaining germline developmental robustness under heat stress. Remarkably, we uncovered that neuronal sRNAs regulate germ cells thermotolerance, affecting both spermatogenic and oogenic germline in a cell non-autonomous manner. Furthermore, we demonstrate that an oxygen-sensing neural circuit antagonizes germline maintenance, likely reflecting the nematodes innate association of reduced oxygen levels with food availability and reproductive permissive environments. Finally, we provide evidence that sRNAs buffer the negative consequences of laboratory domestication, which otherwise cause the laboratory strain to lose germline integrity and become sterile at elevated temperatures. Hence, our findings reveal that mere sensory perception, independent of direct environmental change, modulates germline integrity through sRNA pathways, highlighting a novel mechanism by which neural circuits integrate environmental information to safeguard reproductive fitness in fluctuating environments.

genetics↗

bioRxiv2023

LincRNAs enable germ cells differentiation by promoting PUF proteins condensation

Successful tissue homeostasis depends on a balance between proliferation and differentiation. Two PUF proteins, FBF-1 and FBF-2, maintain stem-cells proliferation in C. elegans germ-cells by binding and destabilizing transcripts which promote meiotic entry. However, it is unclear how meiosis initiates because the FBF are also present at significant levels in late proliferative and early meiotic cells. We found that the three long-intergenic-non-coding RNAs (lincRNAs) that bind the FBF proteins promote timely meiotic entry. Deletion of the lincRNA genes leads to additive reduction in progenitor cell number and fertility. In the lincRNAs deletion mutant, expression of many known FBF-2 targets is significantly lower, suggesting over-activation of FBF-2. In this mutant, FBF-2 localization in perinuclear condensates is reduced, and its cytoplasmic fraction increases. Moreover, FBF-2 association with the germline P-granules decreases without the lincRNAs. Our results indicate that lincRNAs act to promote meiotic differentiation by spatially restricting pro-proliferation factors into phase-separated granules.

developmental biology↗

bioRxiv2020

Chromosome Integrity is Required for the Initiation of Meiotic Sex Chromosome Inactivation in Caenorhabditis elegans

During meiosis of heterogametic cells, such as XY meiocytes, sex chromosomes of many species undergo transcriptional silencing known as meiotic sex chromosome inactivation (MSCI). Silencing also occurs in aberrantly unsynapsed autosomal chromatin. The silencing of unsynapsed chromatin, is assumed to be the underline mechanism for MSCI. Initiation of MSCI is disrupted in meiocytes with sex chromosome-autosome translocations. Whether this is due to aberrant synapsis or the lack of sex chromosome integrity has never been determined. To address this, we used CRISPR to engineer Caenorhabditis elegans stable strains with broken X chromosomes that didnt undergo translocations with autosomes. In early meiotic nuclei of these mutants, the X fragments lack silent chromatin modifications and instead the fragments are enriched with transcribing chromatin modifications. Moreover, the level of active RNA polymerase II staining on the X fragments in mutant nuclei is similar to that on autosomes, indicating active transcription on the X. Contrary to previous models, which predicted that any unsynapsed chromatin is silenced during meiosis, X fragments that did not synapse were robustly stained with RNA polymerase II and gene expression levels were high throughout the broken X. Therefore, lack of synapsis does not trigger MSCI if sex chromosome integrity is lost. Moreover, our results suggest that a unique character of the chromatin of sex chromosomes underlies their lack of meiotic silencing due to both unsynapsed chromatin and sex chromosome mechanisms when their integrity is lost.

cell biology↗

bioRxiv2020

Oocyte Aging is Controlled by Mitogen Activated Protein Kinase Signaling

Oogenesis is one of the first processes to fail during aging. In women, most oocytes cannot successfully complete meiotic divisions during the fourth decade of life. Studies of the nematode Caenorhabditis elegans have uncovered conserved genetic pathways that control lifespan, but our knowledge regarding reproductive aging in worms and humans is limited. Specifically, little is known about germline internal signals that dictate the oogonial biological clock. Here, we report a thorough characterization of the changes in the worm germline during aging. We found that shortly after ovulation halts, germline proliferation declines, while apoptosis continues, leading to a gradual reduction in germ-cell numbers. In late aging stages, we observed that meiotic progression is disturbed and crossover designation and DNA double-strand break repair decrease. In addition, we detected a decline in the quality of mature oocytes during aging, as reflected by decreasing size and elongation of interhomolog distance, a phenotype also observed in human oocytes. Many of these altered processes were previously attributed to MAPK signaling variations in young worms. In support of this, we observed changes in activation dynamics of MPK-1 during aging. We therefore tested the hypothesis that MAPK controls oocyte quality in aged worms using both genetic and pharmacological tools. We found that in mutants with high levels of activated MPK-1, oocyte quality deteriorates more rapidly than in wild-type worms, whereas reduction of MPK-1 levels enhances quality. Thus, our data indicate that MAPK signaling controls germline aging and could be used to attenuate the rate of oogenesis quality decline.

cell biology↗