bims-cebooc Biomed News
on Cell biology of oocytes
Issue of 2025–10–26
sixteen papers selected by
Gabriele Zaffagnini, Universität zu Köln
  1. Nematode telomerase RNA hitchhikes on introns of germline-up-regulated genes.
  2. Live imaging of late-stage preimplantation human embryos reveals de novo mitotic errors.
  3. Phosphoproteomic identification of Mos-MAPK targets in meiotic cell cycle and asymmetric oocyte divisions.
  4. HEIP1 orchestrates pro-crossover protein activity during mammalian meiosis.
  5. EZHIP restricts noncanonical PRC2 binding and regulates H3K27me3 intergenerational inheritance and reprogramming.
  6. Peculiarities of the mammalian oocyte cell cycle.
  7. Poly(U) polymerase activity promotes establishment of primordial germ cells and limits somatic PGL granules in the Caenorhabditis elegans embryo.
  8. A nuclear TRiC/CCT chaperonin assembles meiotic HORMAD proteins into chromosome axes competent for crossing over.
  9. Germ granule localization of nematode Argonaute WAGO-4 ensures fidelity in small RNA loading.
  10. Non-autonomy of age-related morphological changes in the C. elegans germline stem cell niche.
  11. Mechanical coordination between anaphase A and B drives asymmetric chromosome segregation.
  12. Different gametogenesis states uniquely impact longevity in Caenorhabditis elegans.
  13. Structural assembly of the subcortical maternal complex SCMC.
  14. Bloom helicase contributes to successful crossover formation with both catalytic and structural roles in Caenorhabditis elegans meiosis.
  15. Ovarian aging: pathophysiology and recent developments in maintaining ovarian reserve.
  16. Cadherin flow translates cortical chirality into left-right asymmetric cell division dynamics in Caenorhabditis elegans embryos.
  1. Science. 2025 Oct 23. 390(6771): eads7778
    Nematode telomerase RNA hitchhikes on introns of germline-up-regulated genes.
    Yutaka Takeda, Masahiro Onoguchi, Fumiya Ito, Io Yamamoto, Shunsuke Sumi, Tatsuyuki Yoshii, Morié Ishida, Eriko Kajikawa, Jingjing Zhang, Osamu Nishimura, Mitsutaka Kadota, Shunsuke Tagami, Takefumi Kondo, Hirohide Saito, Michiaki Hamada, Hiroki Shibuya.
      Telomerase is a ribonucleoprotein complex that elongates telomeric DNA, ensuring germline immortality. In this study, we identified the Caenorhabditis elegans telomerase RNA component 1 (terc-1), as the first known telomerase RNA expressed as an intronic long noncoding RNA (lncRNA), embedded in an intron of germline-up-regulated gene nmy-2. terc-1 undergoes splicing, polyadenylation, and nuclear RNA exosome-dependent maturation, stabilized by H/ACA small nucleolar ribonucleoproteins, thus co-opting the H/ACA small nucleolar RNA (snoRNA) biogenesis machinery. Mutations in terc-1 led to progressive telomere shortening and sterility in successive generations. Artificially transplanting the nmy-2 intron into the introns of germline-expressed genes but not non-germline-expressed genes restored germline immortality, highlighting the importance of genomic context. Our findings suggest that nematode telomerase RNA is a snoRNA-like intronic lncRNA that exploits the introns of germline-up-regulated genes to ensure species survival.
    DOI:  https://doi.org/10.1126/science.ads7778
  2. Nat Biotechnol. 2025 Oct 23.
    Live imaging of late-stage preimplantation human embryos reveals de novo mitotic errors.
    Ahmed Abdelbaki, Afshan McCarthy, Anita Karsa, Leila Muresan, Kay Elder, Athanasios Papathanasiou, Phil Snell, Leila Christie, Martin Wilding, Benjamin J Steventon, Kathy K Niakan.
      Existing methods to image chromosome segregation errors are not suitable for studying human embryos at advanced preimplantation stages. As chromosomal errors are a leading cause of miscarriage and infertility, it remains unclear whether missegregation arises postfertilization. Here we optimize nuclear DNA labeling via messenger RNA electroporation and apply light-sheet live imaging to reveal chromosome segregation errors immediately before implantation. We show that embryos at advanced preimplantation stages display missegregation, including multipolar spindle formation, lagging chromosomes, misalignment and mitotic slippage. Most lagging chromosomes are passively inherited rather than reincorporated. To trace individual nuclei, we developed an open-source, semi-automated segmentation method using a customized deep learning model optimized for variability in embryo size, shape and signal. With this approach, we find most labeled cells remain externally positioned, consistent with placental rather than inner cell mass fate. Our findings raise questions about clinical uses of preimplantation genetic testing for aneuploidy, while providing broadly applicable imaging and segmentation methods for studying diverse cellular structures in human embryos.
    DOI:  https://doi.org/10.1038/s41587-025-02851-1
  3. J Cell Biol. 2025 Dec 01. pii: e202312140. [Epub ahead of print]224(12):
    Phosphoproteomic identification of Mos-MAPK targets in meiotic cell cycle and asymmetric oocyte divisions.
    Ivan Avilov, Yehor Horokhovskyi, Pooja Mehta, Luisa Welp, Jasmin Jakobi, Mingfang Cai, Aleksander Orzechowski, Henning Urlaub, Juliane Liepe, Peter Lenart.
      The Mos kinase activates the ERK/MAPK pathway during oocyte meiosis, controlling essential meiotic functions in species across metazoa. However, despite its significance, the molecular targets of Mos-MAPK remain largely unidentified. Here, we addressed this question using starfish oocytes ideally suited to combine cellular assays with phosphoproteomics. This revealed CPE-mediated mRNA polyadenylation as a prominent target of Mos-MAPK, and we show that translation is required to drive the second meiotic division. Secondly, we identify a well-defined subset of cytoskeletal regulators as targets of Mos-MAPK. We show that this regulation is critical to ensure the asymmetry of meiotic divisions, primarily by reducing the growth of astral microtubules. This allows positioning of the spindle directly beneath the cortex and prevents the separation of spindle poles in anaphase, thereby minimizing polar body size. Thus, by phosphoproteomics, we reveal molecular modules controlled by Mos-MAPK, explaining how this single, conserved kinase can act as a switch between the mitotic and meiotic division programs.
    DOI:  https://doi.org/10.1083/jcb.202312140
  4. Proc Natl Acad Sci U S A. 2025 Oct 28. 122(43): e2515747122
    HEIP1 orchestrates pro-crossover protein activity during mammalian meiosis.
    Arnaud De Muyt, Sunkyung Lee, Sushil Khanal, Laurine Dal Toe, Céline Adam, Raphael Mercier, Valérie Borde, Neil Hunter, Thomas Robert.
      Meiotic crossovers (COs) are needed to produce genetically balanced gametes. In mammals, CO formation is mediated by a conserved set of pro-CO proteins via mechanisms that remain unclear. Here, we characterize a mammalian pro-CO factor HEIP1. In mouse HEIP1 is essential for crossover and fertility of both sexes. HEIP1 promotes crossover by orchestrating the recruitment of other pro-CO proteins, including the MutSγ complex (MSH4-MSH5) and E3 ligases (HEI10, RNF212, and RNF212B), that are required to mature CO sites and recruit the CO-specific resolution complex MutLγ. Moreover, HEIP1 directly interacts with HEI10, suggesting a direct role in controlling the recruitment of pro-CO E3 ligases. During early stages of meiotic prophase I, HEIP1 interacts with the chromosome axes, independently of recombination, before relocalizing to the central region of the synaptonemal complex. We propose that HEIP1 is a conserved master regulator of CO proteins that controls different CO maturation steps.
    Keywords:  E3-ligases; HEIP1; crossovers; homologous recombination; meiosis
    DOI:  https://doi.org/10.1073/pnas.2515747122
  5. Cell Stem Cell. 2025 Oct 20. pii: S1934-5909(25)00340-6. [Epub ahead of print]
    EZHIP restricts noncanonical PRC2 binding and regulates H3K27me3 intergenerational inheritance and reprogramming.
    Yitian Zeng, Feng Kong, Zihan Xu, Xukun Lu, Qian Li, Bofeng Liu, Shu Liu, Lijun Dong, Ling Liu, Wenying Wang, Bing Zhu, Wei Xie.
      In mice, the repressive histone mark H3K27me3 undergoes both region-specific inheritance and erasure during the parental-to-embryonic transition, with the underlying mechanisms poorly understood. Here, we show that PRC2, which catalyzes H3K27me3, binds both classic Polycomb targets and noncanonical H3K27me3 domains in growing oocytes but dissociates from chromatin in fully grown oocytes. After fertilization, PRC2 rebinds noncanonical H3K27me3 domains before relocating to Polycomb targets in blastocysts. Interestingly, the binding and activity of PRC2 are restricted by a maternal inhibitory factor, EZH inhibitory protein (EZHIP), which co-binds with PRC2. Upon knockout of Ezhip, hyperactive PRC2 promiscuously deposits H3K27me3 genome-wide. This overwrites H3K27me3 memories at noncanonical imprinted genes and paradoxically causes derepression of H3K27me3 targets, defective X chromosome inactivation, and diluted chromatin PRC2. H3K27me3 restoration at Polycomb targets after implantation is also attenuated, accompanied by sub-lethality. These data unveil principles of epigenetic inheritance that both insufficient and excessive heterochromatic marks cause loss of epigenetic memories and repression.
    Keywords:  EZHIP; H3K27me3; Polycomb regulation; early embryo; epigenetic memory; epigenetic reprogramming; intergenerational inheritance; noncanonical imprinting
    DOI:  https://doi.org/10.1016/j.stem.2025.09.009
  6. Physiology (Bethesda). 2025 Oct 21.
    Peculiarities of the mammalian oocyte cell cycle.
    Benjamin Wetherall, Suzanne Madgwick.
      Oocyte meiosis, the process of egg cell formation, requires a highly regulated cell cycle with many unique features compared to somatic cell division. On the journey to create a healthy embryo, this special cell carries a heavy responsibility and must navigate a remarkable number of complex challenges. Most oocytes will never complete this journey, less than 0.1% are ever ovulated, and fewer are viable. However, the few that do complete, manage by the execution of a series of extraordinary adaptations through two rounds of cell division. In this review we discuss some of these challenges and the adaptations that have evolved to mitigate them. This is not intended to be a comprehensive review of the cell cycle in oocytes meiosis, but to highlight some of the differences between oocyte meiosis and a typical mitosis. We discuss features that make this cell unique and the cell cycle regulatory mechanisms that support them. A salute to the few that make it and those that are sacrificed along the way.
    Keywords:  Aneuploidy; Cell cycle; Fertility; Meiosis; Oocyte
    DOI:  https://doi.org/10.1152/physiol.00027.2025
  7. Dev Biol. 2025 Oct 16. pii: S0012-1606(25)00299-4. [Epub ahead of print]
    Poly(U) polymerase activity promotes establishment of primordial germ cells and limits somatic PGL granules in the Caenorhabditis elegans embryo.
    Leanne H Kelley, Ashley S Houlihan, Kevin E Yongblah, Abrar A Aljiboury, Savannah L Davis, Eleanor M Maine.
      Terminal uridylyl transferases/poly(U) polymerases (PUPs) promote animal development. Under conditions of temperature stress, Caenorhabditis elegans PUP-1 and the partially redundant PUP-2 ensure development of the larva/adult germline and embryonic viability. Using high-throughput RNA sequencing, we characterized the transcriptomes of adult hermaphrodites and early embryos lacking PUP-1, PUP-2, or both. Transcripts with altered abundance included those expressed in various somatic tissues or the germline, including neuronal and spermatogenic mRNAs. For some transcripts, abundance was altered only in the absence of both PUP-1 and PUP-2, indicating redundancy. In embryos, some maternally provided and zygotically synthesized mRNAs are elevated, especially in the absence of PUP-2. In the early embryo, PUP-1 promotes division of the germline founder cell (P4), and division failure correlates with adult sterility. PUP-1 promotes the accumulation of PGL-1 in P granules and limits accumulation of somatic PGL-1 foci. Somatic PGL granules are normally cleared by autophagy; loss of PUP-1 does not appear to impair autophagy and instead PGL-1 foci may be more stable due to a change in RNA stability. This work establishes roles for PUPs in early embryonic development that carry forward to adulthood.
    Keywords:  C. elegans; germ granule; poly(U) polymerases PUP-1 and PUP-2; primordial germ cells (PGCs); pup mutant transcriptome; somatic PGL condensate
    DOI:  https://doi.org/10.1016/j.ydbio.2025.10.013
  8. Nat Commun. 2025 Oct 24. 16(1): 9411
    A nuclear TRiC/CCT chaperonin assembles meiotic HORMAD proteins into chromosome axes competent for crossing over.
    Monique Zetka, Amirhossein Pezeshki, Ryan Dawson, Pim J Huis In 't Veld, Steven J M Jones, Nicola Silva.
      The meiotic chromosome axis organizes chromatin and sets the stage for homolog pairing and recombination. Meiotic HORMA domain proteins (mHORMADs) are conserved axis components that conformationally transform during target binding. In C. elegans, four functionally distinct mHORMADs directly interact, but how binding between them is restricted to axis assembly is unknown. Using a mutation in the mHORMADs that delays axis assembly, we isolated a suppressor mutation in a TRiC (Tailless complex peptide 1 Ring Complex) chaperonin subunit that restored mHORMAD localization. CCT-4 associates with meiotic chromatin and forms in vivo complexes with mHORMADs, while germline disruption of TRiC results in axis defects, indicating a nuclear function for TRiC alongside meiotic chromosomes. We propose that chromosome-associated TRiC locally folds mHORMADs into the binding-competent conformation required for axis morphogenesis. More broadly, our results support the model that spatially-restricted folding by TRiC/CCT is a mechanism of controlling the assembly of multimeric complexes that function in tightly co-ordinated events.
    DOI:  https://doi.org/10.1038/s41467-025-64403-0
  9. EMBO J. 2025 Oct 22.
    Germ granule localization of nematode Argonaute WAGO-4 ensures fidelity in small RNA loading.
    Stela Jelenic, Mathias S Renaud, Samantha Del Borrello, Joseph Gokcezade, Janos Bindics, Lisa Frasz, Philipp Czermak, Peter Duchek, Julie M Claycomb.
      Germ granules are liquid-like condensates that regulate small RNA pathways and gene expression, ensuring genome stability and fertility in animals. In C. elegans, several Argonaute proteins, central players of small RNA pathways, localize to germ granules, yet the functional significance of this spatial enrichment remains unclear. Here, we disrupted the localization of the Argonaute WAGO-4 to germ granules by introducing targeted mutations in the FG repeats of Vasa-like GLH proteins. These mutations did not disrupt overall germ granule architecture but significantly reduced WAGO-4 partitioning, leading to its predominant localization in the cytoplasm. Functional analyses revealed that this mislocalization partially compromised WAGO-4 activity, resulting in reduced WAGO-4 binding of small RNAs targeting specific genes, particularly those not co-regulated by the Argonaute CSR-1. This selective effect highlights the importance of WAGO-4's spatial localization for efficient small RNA loading and gene regulation. Our findings demonstrate that germ granules serve as specialized compartments that fine-tune Argonaute function, emphasizing the role of phase-separated condensates in modulating RNA pathways and gene regulatory networks.
    Keywords:   C. elegans Germline; Argonautes; Biomolecular Condensates; Germ Granules; Small RNA Pathways
    DOI:  https://doi.org/10.1038/s44318-025-00606-x
  10. Development. 2025 Oct 15. pii: dev204970. [Epub ahead of print]152(20):
    Non-autonomy of age-related morphological changes in the C. elegans germline stem cell niche.
    Nilay Gupta, Mia Sinks, E Jane Albert Hubbard.
      Declines in tissue renewal and repair due to alterations in tissue stem cells is a hallmark of aging. Many stem cell pools are maintained by morphologically complex niches. Using the C. elegans hermaphrodite germline stem cell system, we analyzed age-related changes in the morphology of the niche, the distal tip cell (DTC), and identified a molecular mechanism that promotes a subset of these changes. We found decreases in the number and length of long DTC processes with age. We also found that a long-lived daf-2 mutant exhibits a daf-16-dependent maintenance of long DTC processes. Surprisingly, the tissue requirement for daf-16(+) is non-autonomous, and daf-16(+) in body wall muscle is both necessary and sufficient. In addition, after a delay, pre-formed DTC processes deteriorate upon premature germline differentiation, but not upon cell cycle inhibition. We propose a reciprocal DTC-germline interaction model and speculate how reduced daf-2 activity both delays stem cell exhaustion and maintains DTC processes. These studies establish the C. elegans DTC as a powerful in vivo model for understanding age-related changes in cellular morphology and their consequences in stem cell systems.
    Keywords:   glp-4 ; Aging; DAF-16/FOXO; Distal tip cell (DTC); Insulin/IGF-like signaling (IIS); Stem cell
    DOI:  https://doi.org/10.1242/dev.204970
  11. J Cell Biol. 2026 Jan 05. pii: e202505038. [Epub ahead of print]225(1):
    Mechanical coordination between anaphase A and B drives asymmetric chromosome segregation.
    Ana M Dias Maia Henriques, Timothy R Davies, Serge Dmitrieff, Nicolas Minc, Julie C Canman, Julien Dumont, Gilliane Maton.
      Chromosome segregation during anaphase occurs through two mechanistically distinct processes: anaphase A, in which chromosomes move toward spindle poles, and anaphase B, in which the anaphase spindle elongates through cortical astral microtubule pulling forces. Caenorhabditis elegans embryos have been thought to rely primarily on anaphase B, with little to no contribution from anaphase A. Here, we uncover a novel anaphase A mechanism in C. elegans embryos, driven by the kinesin-13 KLP-7MCAK and opposed by the kinesin-12 KLP-18. We found that the extent of chromosome segregation during anaphase A is asymmetrically regulated by cell polarity cues and modulated by mechanical tension within the spindle, generated by opposing forces acting on chromosomes and spindle poles. Additionally, we found that the contribution of anaphase A to chromosome segregation increases progressively across early embryonic divisions. These findings uncover an unexpected role for anaphase A in early C. elegans development and reveal a KLP-7MCAK-dependent mechanical coordination between anaphase A- and anaphase B-driven chromosome segregation.
    DOI:  https://doi.org/10.1083/jcb.202505038
  12. Nat Commun. 2025 Oct 21. 16(1): 9300
    Different gametogenesis states uniquely impact longevity in Caenorhabditis elegans.
    Amaresh Chaturbedi, Siu Sylvia Lee.
      Reproduction affects lifespan and fat metabolism across species, suggesting a shared regulatory axis. In Caenorhabditis elegans, ablation of germline stem cells leads to extended lifespan and increased fat storage. While many studies focus on germline-less glp-1(e2144) mutants, the hermaphroditic germline of C. elegans provides an excellent opportunity to study how distinct germline anomalies affect lifespan and fat metabolism. We compare metabolomic, transcriptomic, and genetic pathway differences among three sterile mutants: germline-less glp-1, feminized fem-3, and masculinized mog-3. All three accumulate excess fat and share expression changes in stress response and metabolism genes. However, glp-1 mutants exhibit the most robust lifespan extension, fem-3 mutants live longer only at certain temperatures, and mog-3 mutants are markedly short-lived. The extended lifespan in fem-3 mutants require daf-16/FOXO, as in glp-1 mutants. In contrast, daf-16 is dispensable for the already shortened lifespan of mog-3 mutants. Interestingly, mog-3 partially mimics male/mating-induced demise, offering a simplified model to study metabolic and reproductive trade-offs underlying this phenomenon. Our data indicate that disrupting specific germ cell populations leads to distinct and complex physiological and longevity outcomes. These findings highlight the importance of investigating sex-dependent differences and underlying mechanisms to fully understand and potentially modulate these relationships.
    DOI:  https://doi.org/10.1038/s41467-025-64341-x
  13. Structure. 2025 Oct 20. pii: S0969-2126(25)00375-2. [Epub ahead of print]
    Structural assembly of the subcortical maternal complex SCMC.
    Guojin Ou, Qingting Liu, Haizhan Jiao, Zhuo Han, Jinhong Li, Ling Min, Pengliang Chi, Sibei Liu, Jialu Li, Qianqian Qi, Zihan Zhang, Li Guo, Xiang Wang, Lei Li, Jing Chen, Hongli Hu, Dong Deng.
      The subcortical maternal complex (SCMC) is essential for mammalian preimplantation development, yet how SCMCcore (MATER/NLRP5, TLE6, FLOPED/OOEP) engages regulatory partners remains unclear. We determined cryo-EM structures of mouse SCMC bound to ZBED3 and human SCMC bound to NLRP2. Our structure reveals that ZBED3 interacts with all three SCMCcore subunits via its zinc finger domain, with conserved residue Phe73 mediating specific contacts. In contrast, human NLRP2 only binds to the WD40 domain of TLE6 through its leucine-rich repeat (LRR) domain. Similar interactions were also confirmed for NLRP7 with TLE6. These findings were cross-validated by in vivo proximity ligation and in vitro pull-down assays. Our work proposes a paradigmatic "Lego-like" assembly model, where the SCMCcore sequentially recruits different partners through diverse molecular interfaces. These findings provide critical structural insights into the SCMC's architecture and its multifaceted regulatory roles in early mammalian embryogenesis.
    Keywords:  Lego-like assembly model; cryo-EM; early mammalian embryogenesis; pathogenic variants; subcortical maternal complex
    DOI:  https://doi.org/10.1016/j.str.2025.09.009
  14. Nucleic Acids Res. 2025 Oct 14. pii: gkaf1030. [Epub ahead of print]53(19):
    Bloom helicase contributes to successful crossover formation with both catalytic and structural roles in Caenorhabditis elegans meiosis.
    Sowmya Sivakumar Geetha, Ivana Čavka, Maria Rosaria Dello Stritto, Angela Graf, Tomas Macha, Hannah Krakolinig, Simone Köhler, Verena Jantsch.
      Crossover (CO)-biased repair of meiotic DNA double-strand breaks is essential for proper chromosome segregation. However, only a subset of programmed induced DSBs is repaired as COs, while the rest is processed into non-COs. The Bloom-Topoisomerase 3-RMI1/2 complex is well documented to disassemble joint recombination intermediates into non-COs, but its pro-CO activities are less well understood. Here, we investigate how the pro-CO activities of the Caenorhabditis elegans Bloom helicase ortholog HIM-6 contribute to meiotic recombination by studying a catalytically inactive mutant. We show that HIM-6 helicase activity is required to provide a continuous flux of substrates for CO formation, probably via its unwinding activities, and that a structural role is sufficient to channel intermediates into the preferred pathway to generate correctly positioned COs. We provide evidence that the catalytic activity of Bloom helicase influences the geometry of the joint DNA molecules (double Holliday junctions (dHJ)). Localization of the signal for the dHJ-stabilizing complex MutSγ was more restricted, and epistasis experiments suggest that an altered geometry impedes the efficient processing of joint DNA molecules to generate CO-biased cleavage products.
    DOI:  https://doi.org/10.1093/nar/gkaf1030
  15. Front Endocrinol (Lausanne). 2025 ;16 1619516
    Ovarian aging: pathophysiology and recent developments in maintaining ovarian reserve.
    Mana Hirano, Takako Onodera, Kazuki Takasaki, Yuko Takahashi, Takayuki Ichinose, Haruka Nishida, Haruko Hiraike, Kazunori Nagasaka.
      According to the World Health Organization, infertility has emerged as a critical public health issue, affecting approximately 48 million couples and 186 million individuals worldwide. Ovarian aging-defined by the progressive depletion and functional deterioration of the primordial follicle pool-accounts for a major proportion of female-factor infertility and has profound socioeconomic consequences. It is characterized by a decline in follicle quantity and quality, which significantly influences infertility. This phenomenon is multifaceted, involving genetic predisposition, hormonal fluctuations, mitochondrial dysfunction, oxidative stress, and ovarian microenvironment alterations. This review explores the biological mechanisms of ovarian aging, evaluates current therapeutic advances, and identifies strategies to maintain ovarian function and prolong reproductive lifespan. Recent advancements-including antioxidant and mitochondria-targeted therapies, hormonal modulation, growth factor interventions (e.g., platelet-rich plasma), mitochondrial transfer, and in vitro follicle activation-show promise for maintaining ovarian reserve. Fertility preservation strategies, such as ovarian tissue cryopreservation and transplantation, and pharmacological inhibition of follicle depletion, have expanded therapeutic options. The development of personalized treatments, refined biomarkers, and integrative strategies combining antioxidants, hormonal therapies, and novel fertility preservation techniques is essential. Therefore, translational research utilizing animal models remains crucial for validating efficacy and safety prior to clinical application. Future research should prioritize validating these emerging therapies through larger clinical trials to ensure safe, effective, and practical translation into clinical practice, ultimately prolonging reproductive lifespan and enhancing quality of life for aging women.
    Keywords:  biomarker-driven; delayed parenthood; fertility preservation; follicle depletion; hormonal therapies; menopause; ovarian aging; ovarian reserve
    DOI:  https://doi.org/10.3389/fendo.2025.1619516
  16. Curr Biol. 2025 Oct 22. pii: S0960-9822(25)01252-7. [Epub ahead of print]
    Cadherin flow translates cortical chirality into left-right asymmetric cell division dynamics in Caenorhabditis elegans embryos.
    Mi Jing Khor, Yuxuan Rain Xiong, Gaganpreet Sangha, Kenji Sugioka.
      Diverse strategies have evolved in bilaterians to establish left-right (L-R) asymmetry. One driver of L-R asymmetry conserved across phyla is the chiral mechanics of the actomyosin-rich cell cortex, a surface layer that governs cell shape and dynamics. However, how cortical chirality is converted into cellular L-R asymmetry remains obscure. Here, we identify cortical-flow-dependent chiral adhesion pattern formation as a key mechanism driving L-R symmetry breaking of cell division in the two-cell-stage Caenorhabditis elegans embryo. Using high-resolution 4D imaging, we show that the classical cadherin HMR-1 exhibits an early ventral flow followed by a later L-R asymmetric flow during cytokinesis. These ventral and chiral cadherin flows, driven by the extracellular matrix coat surrounding the embryos and by RhoA signaling, respectively, together generate a chiral cadherin pattern at the cell-cell contact. The chiral cadherin patch interacts asymmetrically with the cytokinetic contractile ring, selectively slowing its closure on the embryo's right side via inhibition of ring-directed cortical flow. Disrupting cadherin flow or its interaction with the ring abolishes the rightward displacement of the contractile ring-the earliest detectable L-R asymmetry in C. elegans development. Although cadherin flow is known to facilitate junctional remodeling across organisms, our findings reveal its unexpected role in translating cortical chirality into asymmetric cell division dynamics.
    Keywords:  C. elegans; cadherin; cell division; cell-cell adhesion; chirality; cortical flow; cytokinesis; cytoskeleton; left-right asymmetry
    DOI:  https://doi.org/10.1016/j.cub.2025.09.052
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