bims-cebooc Biomed News
on Cell biology of oocytes
Issue of 2025–04–06
twenty papers selected by
Gabriele Zaffagnini, Universität zu Köln
  1. Direct cell-to-cell transmission of retrotransposons.
  2. Atomic Force Microscopy Reveals Differences In Mechanical Properties Linked To Cortical Structure In Mouse And Human Oocytes.
  3. DDX5 regulates asymmetric division of mouse oocytes by modulating the stability of microfilament-associated protein radixin.
  4. Meiotic cohesion requires Sirt1 and preserving its activity in aging oocytes reduces missegregation.
  5. The TRPV3 channel is a mediator of zinc influx and homeostasis in murine oocytes.
  6. Cellular and molecular regulations of oocyte selection and activation in mammals.
  7. Luteinizing hormone-induced changes in the structure of mammalian preovulatory follicles.
  8. No transcription, no problem: Protein phosphorylation changes and the transition from oocyte to embryo.
  9. The mammalian egg's zona pellucida, fertilization, and fertility.
  10. Paternal contributions to mammalian zygote - Beyond sperm-oocyte fusion.
  11. Epigenome dynamics in early mammalian embryogenesis.
  12. The genetics of preimplantation embryonic arrest: the role of aneuploidies.
  13. Activating the C. elegans egg: Molecular players, current knowledge, and unanswered questions.
  14. Fertilization and the fast block to polyspermy in the African Clawed Frog, Xenopus laevis: A historical perspective.
  15. Fertilization mechanisms in hermaphroditic ascidians and nematodes: Common mechanisms with mammals and plants.
  16. Origin and establishment of the germline in Drosophila melanogaster.
  17. TORC1-driven translation of Nucleoporin44A promotes chromatin remodeling and germ cell-to-maternal transition in Drosophila.
  18. Multiple domains of scaffold Tudor protein play non-redundant roles in Drosophila germline.
  19. Topoisomerase 3b facilitates piRNA biogenesis to promote transposon silencing and germ cell development.
  20. Fusome morphogenesis is sufficient to promote female germline stem cell self-renewal in Drosophila.
  1. bioRxiv. 2025 Mar 16. pii: 2025.03.14.642691. [Epub ahead of print]
    Direct cell-to-cell transmission of retrotransposons.
    Maya Voichek, Andreas Bernhard, Maria Novatchkova, Dominik Handler, Paul Möseneder, Baptiste Rafanel, Peter Duchek, Kirsten-André Senti, Julius Brennecke.
      Transposable elements are abundant in host genomes but are generally considered to be confined to the cell in which they are expressed, with the notable exception of endogenous retroviruses. Here, we identify a group of LTR retrotransposons that infect the germline from somatic cells within the Drosophila ovary, despite lacking the fusogenic Envelope protein typically required for retroviral entry. Instead, these elements encode a short transmembrane protein, sORF2, with structural features reminiscent of viral cell-cell fusogens. Through genetics, imaging, and electron microscopy, we show that sORF2 localizes to invasive somatic protrusions, enabling the direct transfer of retrotransposon capsids into the oocyte. Remarkably, sORF2-like proteins are widespread among insect retrotransposons and also occur in piscine nackednaviruses and avian picornaviruses. These findings reveal a noncanonical, Envelope-independent transmission mechanism shared by retrotransposons and non-enveloped viruses, offering important insights into host-pathogen evolution and soma-germline interactions.
    DOI:  https://doi.org/10.1101/2025.03.14.642691
  2. Small. 2025 Mar 30. e2500221
    Atomic Force Microscopy Reveals Differences In Mechanical Properties Linked To Cortical Structure In Mouse And Human Oocytes.
    Rose Bulteau, Lucie Barbier, Guillaume Lamour, Yassir Lemseffer, Marie-Hélène Verlhac, Nicolas Tessandier, Elsa Labrune, Martin Lenz, Marie-Emilie Terret, Clément Campillo.
      Cell mechanical properties regulate biological processes such as oocyte development. Cortical tension is regulated via actomyosin cortex remodeling to ensure optimal oocyte quality. However, the evolution of other mechanical parameters and their relationship with cortex structure remain poorly understood in mammalian oocytes. In this work, a methodology combining multiple mechanical parameters measured through Atomic Force Microscopy is proposed to investigate the relationship between oocyte mechanical properties and cortex organization. By studying mouse oocytes at various stages of development, along with engineered ones with specific cortex organization, it is demonstrated that a thin actin cortex corresponds to stiff oocytes while a thick one is associated with softer oocytes. It is further revealed that maternal age, a critical factor for fertility, affects mouse oocytes mechanics, correlating with alterations in their cortex structure. Finally, it is shown that the evolution of mechanical properties differs between human and mouse oocyte development, highlighting species-specific differences in cortex organization.
    Keywords:  actomyosin cortex; atomic force microscopy; biomechanics; cortical tension; elastic modulus; oocytes
    DOI:  https://doi.org/10.1002/smll.202500221
  3. Theriogenology. 2025 Mar 24. pii: S0093-691X(25)00127-X. [Epub ahead of print]240 117401
    DDX5 regulates asymmetric division of mouse oocytes by modulating the stability of microfilament-associated protein radixin.
    Lina Yu, Ruixin Shi, Yan Mao, Aolei Guo, Lihua Zhu, Guangyi Cao.
      Mammalian oocytes arrest at prophase I and resume meiosis upon germinal vesicle breakdown, leading to asymmetric division and formation of a smaller polar body and larger oocyte, crucial for genome segregation and cytoplasmic distribution. Actin filaments regulate this division, with reorganization involving actin cap formation and cytoplasmic network changes, mediated by actin-binding proteins like myosins and radixin. DDX5, an RNA helicase, is implicated in transcription, RNA metabolism, and early embryonic development, though its regulatory mechanisms in oocyte maturation remain unclear. Here, we demonstrate that DDX5 regulates cytokinesis during mouse oocyte meiotic maturation. DDX5 colocalizes with the spindle upon meiotic resumption, and its inhibition impairs polar body extrusion and cytokinesis. RNA-seq reveals disrupted mRNA homeostasis upon DDX5 depletion, while IP-MS identifies its interaction with actin cytoskeletal proteins, including radixin, whose expression is significantly reduced. Our findings reveal that DDX5 modulates oocyte cytokinesis by regulating actin cytoskeleton dynamics, underscoring its critical role in asymmetric division.
    Keywords:  Cytokinesis; Cytoskeleton; DDX5; Meiosis; Oocyte
    DOI:  https://doi.org/10.1016/j.theriogenology.2025.117401
  4. bioRxiv. 2025 Mar 14. pii: 2025.03.12.642822. [Epub ahead of print]
    Meiotic cohesion requires Sirt1 and preserving its activity in aging oocytes reduces missegregation.
    Zihan Meng 姿 含 孟, Nicholas G Norwitz, Sharon E Bickel.
      Chromosome segregation errors in human oocytes increase dramatically as women age and premature loss of meiotic cohesion is one factor that contributes to a higher incidence of segregation errors in older oocytes. Here we show that cohesion maintenance during meiotic prophase in Drosophila oocytes requires the NAD+-dependent deacetylase, Sirt1. Knockdown of Sirt1 during meiotic prophase causes premature loss of arm cohesion and chromosome segregation errors. We have previously demonstrated that when Drosophila oocytes arrest and age in diplotene, segregation errors increase significantly. By quantifying acetylation of the Sirt1 substrate H4K16 on oocytes chromosomes, we find that Sirt1 deacetylase activity declines markedly during aging. However, if females are fed the Sirt1 activator SRT1720 as their oocytes age, the H4K16ac signal on oocyte DNA remains low in aged oocytes, consistent with preservation of Sirt1 activity during aging. Strikingly, age-dependent segregation errors are significantly reduced if mothers are fed SRT1720 while their oocytes age. Our data suggest that maintaining Sirt1 activity in aging oocytes may provide a viable therapeutic strategy to decrease age-dependent segregation errors.
    Keywords:  Drosophila; SRT1720; maternal age effect; meiosis; sister chromatid cohesion
    DOI:  https://doi.org/10.1101/2025.03.12.642822
  5. Proc Natl Acad Sci U S A. 2025 Apr 08. 122(14): e2420194122
    The TRPV3 channel is a mediator of zinc influx and homeostasis in murine oocytes.
    Emily M Lopes, Hiroki Akizawa, Oguz C Koc, Edgar Soto-Moreno, Neha Gupta, Goli Ardestani, Ahmed Z Balboula, Ingrid Carvacho, Rafael A Fissore.
      Zinc (Zn2+) homeostasis is essential for gametogenesis and reproduction, and its deficiency causes infertility. Oocytes contain higher Zn2+ levels than somatic cells, and Zn2+ concentrations in oocytes are far higher than those of other transition metals and increase even more during maturation in preparation for fertilization. Remarkably, it is unknown what transporter(s) or channel(s) mediate Zn2+ influx in oocytes and whether they are expressed uniformly throughout folliculogenesis. Here, we showed that the functional expression of a member of the transient receptor potential family, vanilloid 3, TRPV3, closely follows the dynamics of intracellular Zn2+ during oocyte maturation, raising the prospect that these events may be functionally linked. Using microfluorometry, we monitored in oocytes of Trpv3 null females the expected rise in Zn2+ concentrations during maturation. Surprisingly, Zn2+ levels did not climb, and the overall FluoZin3 signal in Trpv3 null eggs was lower than in control eggs. Electrophysiological recordings showed a large TRPV3 current induced by the agonist 2-APB in WT eggs supplemented with extracellular Zn2+ that was absent in Trpv3 null eggs; TRPV3 showed a clear preference for Zn2+ over Ca2+. Trpv3 null eggs displayed features associated with Zn2+ deficient conditions, such as lower IP3R1 function, abnormal cortical granule distribution, and disturbed cytoskeletal organization with distinct actin nucleation disorders. Notably, Trpv3 null eggs demonstrated undisturbed Zn2+ sparks. Our results suggest that TRPV3 is a pivotal member of the Zn2+ toolkit, mediating Zn2+ intake during maturation. They also indicate that distinct transporters or channels mediate Zn2+ influx throughout folliculogenesis.
    Keywords:  Trp channels; actin; fertilization; oocyte maturation; whole-cell patch clamp
    DOI:  https://doi.org/10.1073/pnas.2420194122
  6. Curr Top Dev Biol. 2025 ;pii: S0070-2153(24)00114-5. [Epub ahead of print]162 283-315
    Cellular and molecular regulations of oocyte selection and activation in mammals.
    Xuebing Yang, Yan Zhang, Hua Zhang.
      Oocytes, a uniquely pivotal cell population, play a central role in species continuity. In mammals, oogenesis involves distinct processes characterized by sequential rounds of selection, arrest, and activation to produce a limited number of mature eggs, fitting their high-survival yet high-cost fertility. During the embryonic phase, oocytes undergo intensive selection via cytoplasmic and organelle enrichment, accompanied by the onset and arrest of meiosis, thereby establishing primordial follicles (PFs) as a finite reproductive reserve. Subsequently, the majority of primary oocytes enter a dormant state and are gradually recruited through a process termed follicle activation, essential for maintaining orderly fertility. Following activation, oocytes undergo rapid growth, experiencing cycles of arrest and activation regulated by endocrine and paracrine signals, ultimately forming fertilizable eggs. Over the past two decades, advancements in genetically modified animal models, high-resolution imaging, and omics technologies have significantly enhanced our understanding of the cellular and molecular mechanisms that govern mammalian oogenesis. These advances offer profound insights into the regulatory mechanisms of mammalian reproduction and associated female infertility disorders. In this chapter, we provide an overview of current knowledge in mammalian oogenesis, with a particular emphasis on oocyte selection and activation in vivo.
    Keywords:  Oocyte activation; Oocyte dormancy; Oogenesis; Ovarian reserve; Primordial follicle
    DOI:  https://doi.org/10.1016/bs.ctdb.2024.11.003
  7. Curr Top Dev Biol. 2025 ;pii: S0070-2153(24)00111-X. [Epub ahead of print]162 259-282
    Luteinizing hormone-induced changes in the structure of mammalian preovulatory follicles.
    Corie M Owen, Laurinda A Jaffe.
      Ovulation of a mammalian oocyte from its follicle, which occurs in response to luteinizing hormone (LH), requires complex restructuring of the ∼20 layers of surrounding somatic cells. This chapter describes the cellular architecture of preovulatory follicles, the localization of the receptors for LH, and the LH-induced changes in follicular structure, focusing on mice and other small mammals. The multiple interrelated processes that result in ovulation include breakdown of existing extracellular matrix, generation of new extracellular matrix, thinning of the follicular apex where the oocyte will be released, invagination of the follicular surface, and responses of the vascular system to support these dynamic changes. However, much remains unknown about how these events function together to release a fertilizable egg.
    Keywords:  Luteinizing hormone; Mammal; Ovary; Ovulation; Preovulatory follicle
    DOI:  https://doi.org/10.1016/bs.ctdb.2024.10.011
  8. Curr Top Dev Biol. 2025 ;pii: S0070-2153(25)00010-9. [Epub ahead of print]162 165-205
    No transcription, no problem: Protein phosphorylation changes and the transition from oocyte to embryo.
    Jonathon M Thomalla, Mariana F Wolfner.
      Although mature oocytes are arrested in a differentiated state, they are provisioned with maternally-derived macromolecules that will start embryogenesis. The transition to embryogenesis, called 'egg activation', occurs without new transcription, even though it includes major cell changes like completing stalled meiosis, translating stored mRNAs, cytoskeletal remodeling, and changes to nuclear architecture. In most animals, egg activation is triggered by a rise in free calcium in the egg's cytoplasm, but we are only now beginning to understand how this induces the egg to transition to totipotency and proliferation. Here, we discuss the model that calcium-dependent protein kinases and phosphatases modify the phosphorylation landscape of the maternal proteome to activate the egg. We review recent phosphoproteomic mass spectrometry analyses that revealed broad phospho-regulation during egg activation, both in number of phospho-events and classes of regulated proteins. Our interspecies comparisons of these proteins pinpoints orthologs and protein families that are phospho-regulated in activating eggs, many of which function in hallmark events of egg activation, and others whose regulation and activity warrant further study. Finally, we discuss key phospho-regulating enzymes that may act apically or as intermediates in the phosphorylation cascades during egg activation. Knowing the regulators, targets, and effects of phospho-regulation that cause an egg to initiate embryogenesis is crucial at both fundamental and applied levels for understanding female fertility, embryo development, and cell-state transitions.
    Keywords:  Calcineurin; Calcium; CamKII; Egg activation; Embryogenesis; Fertilization; Meiotic arrest; Oocyte; Post-translational control; Protein phosphorylation; Translation; Zygote
    DOI:  https://doi.org/10.1016/bs.ctdb.2025.01.001
  9. Curr Top Dev Biol. 2025 ;pii: S0070-2153(24)00108-X. [Epub ahead of print]162 207-258
    The mammalian egg's zona pellucida, fertilization, and fertility.
    Eveline S Litscher, Paul M Wassarman.
      The zona pellucida (ZP) is a relatively thick extracellular matrix (ECM) that surrounds all mammalian eggs and plays vital roles during oogenesis, fertilization, and preimplantation development. The ZP is a semi-permeable, viscous ECM that consists of three or four glycosylated proteins, called ZP1-4, that differ from proteoglycans and proteins of somatic cell ECM. Mammalian ZP proteins are encoded by single-copy genes on different chromosomes and synthesized and secreted by growing oocytes arrested in meiosis. Secreted ZP proteins assemble in the extracellular space into long fibrils that are crosslinked polymers of ZP proteins and exhibit a structural repeat. Several regions of nascent ZP proteins, the signal-sequence, ZP domain, internal and external hydrophobic patches, transmembrane domain, and consensus furin cleavage-site regulate secretion and assembly of the proteins. The ZP domain is required for assembly of ZP fibrils, as well as for assembly of other kinds of ZP domain-containing proteins. ZP proteins adopt immunoglobulin (Ig)-like folds that resemble C- and V-type Ig-like domains, but represent new immunoglobulin-superfamily subtype structures. Interference with synthesis, processing, or secretion of ZP proteins by either gene-targeting in mice or mutations in human ZP genes can result in failure to assemble a ZP and female infertility. ZP2 and ZP3 must be present to assemble a ZP during oocyte growth and both serve as receptors for binding of free-swimming sperm to ovulated eggs. Acrosome-reacted sperm bind to ZP2 polypeptide by inner-acrosomal membrane and acrosome-intact sperm bind to ZP3 oligosaccharides by plasma membrane overlying the sperm head. Binding of acrosome-intact sperm to ZP3 induces them to undergo cellular exocytosis, the acrosome reaction. Only acrosome-reacted sperm can penetrate the ZP, bind to, and then fuse with the egg's plasma membrane to produce a zygote. Following sperm-egg fusion (fertilization) the ZP undergoes structural and functional changes (zona reaction) induced by cortical granule components (cortical reaction) deposited into the ZP. The latter include zinc and ovastacin, a metalloendoprotease that cleaves ZP2 near its amino-terminus and hardens the egg's ZP. The changes prevent penetration of bound sperm through and binding of supernumerary sperm to the ZP of fertilized eggs as part of a secondary or slow block to polyspermy. Therefore, ZP proteins act as structural proteins and sperm receptors, and help to prevent fertilization by more than one sperm. Here we review some of this information and provide details about several key features of ZP proteins, ZP matrix, and mammalian fertilization.
    DOI:  https://doi.org/10.1016/bs.ctdb.2024.10.008
  10. Curr Top Dev Biol. 2025 ;pii: S0070-2153(25)00038-9. [Epub ahead of print]162 387-446
    Paternal contributions to mammalian zygote - Beyond sperm-oocyte fusion.
    Peter Sutovsky, Michal Zigo, Filip Tirpak, Richard Oko.
      Contrary to a common misconception that the fertilizing spermatozoon acts solely as a vehicle for paternal genome delivery to the zygote, this chapter aims to illustrate how the male gamete makes other essential contributions , including the sperm borne-oocyte activation factors, centrosome components, and components of the sperm proteome and transcriptome that help to lay the foundation for pregnancy establishment and maintenance to term, and the newborn and adult health. Our inquiry starts immediately after sperm plasma membrane fusion with its oocyte counterpart, the oolemma. Parallel to and following sperm incorporation in the egg cytoplasm, some of the sperm structures (perinuclear theca) are dissolved and spent to induce development, others (nucleus, centriole) are transformed into zygotic structures enabling it, and yet others (mitochondrial and fibrous sheath, axonemal microtubules and outer dense fibers) are recycled as to not stand in its way. Noteworthy advances in this research include the identification of several sperm-borne oocyte activating factor candidates, the role of autophagy in the post-fertilization sperm mitochondrion degradation, new insight into zygotic centrosome origins and function, and the contributions of sperm-delivered RNA cargos to early embryo development. In concluding remarks, the unresolved issues, and clinical and biotechnological implications of sperm-vectored paternal inheritance are discussed.
    Keywords:  Acrosome; Centrosome; Fertilization; Fibrous sheath; Infertility; Inheritance; Mitochondria; Outer dense fibers; Perinuclear theca; RNA; Sperm
    DOI:  https://doi.org/10.1016/bs.ctdb.2025.02.002
  11. Nat Rev Genet. 2025 Apr 03.
    Epigenome dynamics in early mammalian embryogenesis.
    Adam Burton, Maria-Elena Torres-Padilla.
      During early embryonic development in mammals, the totipotency of the zygote - which is reprogrammed from the differentiated gametes - transitions to pluripotency by the blastocyst stage, coincident with the first cell fate decision. These changes in cellular potency are accompanied by large-scale alterations in the nucleus, including major transcriptional, epigenetic and architectural remodelling, and the establishment of the DNA replication programme. Advances in low-input genomics and loss-of-function methodologies tailored to the pre-implantation embryo now enable these processes to be studied at an unprecedented level of molecular detail in vivo. Such studies have provided new insights into the genome-wide landscape of epigenetic reprogramming and chromatin dynamics during this fundamental period of pre-implantation development.
    DOI:  https://doi.org/10.1038/s41576-025-00831-4
  12. Curr Opin Obstet Gynecol. 2025 Mar 24.
    The genetics of preimplantation embryonic arrest: the role of aneuploidies.
    Ludovica Picchetta, Katharina Spath, Antonio Capalbo, Christian Simon Ottolini.
       PURPOSE OF THE REVIEW: Aneuploidy is a major cause of embryonic arrest. While meiotic aneuploidies, especially maternal, are a well-documented cause of embryo and fetal arrest, increasing evidence highlights the crucial role played by mitotic aneuploidies. This review explores the molecular and cellular pathways underlying these abnormalities, focusing on abnormal cleavage, chromatin cohesion, spindle stability, maternal effect genes, and mitochondria.
    RECENT FINDINGS: Approximately half of human embryos cease development in vitro or shortly after transfer to the uterus. Genetic investigation of these embryos has highlighted that 90% of these exhibit aneuploidies. Surprisingly, most of these arise from errors during the early mitotic divisions of preimplantation embryos. These findings strongly correlate with disruptions of early cleavage possibly due to faulty spindle assembly or mitochondrial dysfunction during the in-vitro development. Moreover, maternal effects, such as faulty meiotic recombination and variants in maternal effect genes involved in the subcortical maternal complex, may further predispose the embryo to high rates of chromosomal imbalance.
    SUMMARY: Meiotic and mitotic aneuploidies play a significant role in embryo arrest, yet their molecular and cellular origin are not well understood. Investigating these pathways may lead to interventions that could be developed to improve success rates with IVF or even fertility rates in general.
    DOI:  https://doi.org/10.1097/GCO.0000000000001020
  13. Curr Top Dev Biol. 2025 ;pii: S0070-2153(25)00018-3. [Epub ahead of print]162 115-141
    Activating the C. elegans egg: Molecular players, current knowledge, and unanswered questions.
    Aimee Jaramillo-Lambert, Amber R Krauchunas.
      Egg activation is a global cellular change that, in combination with fertilization, transitions the differentiated, developmentally quiescent oocyte into a totipotent, developmentally active one-cell embryo. In C. elegans, key regulators of egg activation include egg-3, egg-4, egg-5, chs-1, and spe-11. Here we will review our current understanding of how these molecules, and others, ensure the robust activation of the egg by controlling meiosis, formation of the eggshell, and the block to polyspermy.
    Keywords:  C. elegans; Calcium; EGG complex; Egg; Egg activation; Eggshell; Oocyte-to-embryo transition; Polyspermy; Spe
    DOI:  https://doi.org/10.1016/bs.ctdb.2025.01.007
  14. Curr Top Dev Biol. 2025 ;pii: S0070-2153(24)00125-X. [Epub ahead of print]162 143-163
    Fertilization and the fast block to polyspermy in the African Clawed Frog, Xenopus laevis: A historical perspective.
    Kayla M Komondor, Anne E Carlson.
      The African clawed frog, Xenopus laevis, has long been a model organism for studying fertilization due to its large and abundant eggs that are easily manipulated and rapidly undergo embryonic development. Research on this model organism has provided significant insights into the mechanisms that ensure successful fertilization, including the prevention of polyspermy. Polyspermy, the fertilization of an egg by multiple sperm, poses a significant threat to successful embryonic development in most sexually reproducing animals. To counter this, eggs have evolved mechanisms known as polyspermy blocks, which prevent additional sperm from entering once fertilization has occurred. This review focuses on fertilization research in general, and specifically on studies of the fast block to polyspermy in X. laevis. We trace key discoveries and experimental advancements that have shaped our current understanding. Indeed, studies on X. laevis have revealed that fertilization triggers a depolarization of the egg membrane mediated by an efflux of Cl- through the Ca2+-activated Cl- channel TMEM16A, effectively preventing polyspermy. Despite these advances, several questions remain regarding the precise molecular interactions and signaling pathways involved. Continued research on X. laevis promises to uncover further details about the earliest events in embryogenesis and the voltage-dependent mechanisms of fertilization, offering broader insights into reproductive biology across species.
    Keywords:  Egg; Fast block; Fertilization; Polyspermy; Sperm; Xenopus laevis
    DOI:  https://doi.org/10.1016/bs.ctdb.2024.12.003
  15. Curr Top Dev Biol. 2025 ;pii: S0070-2153(25)00036-5. [Epub ahead of print]162 55-114
    Fertilization mechanisms in hermaphroditic ascidians and nematodes: Common mechanisms with mammals and plants.
    Hitoshi Sawada, Takako Saito, Yoshihiro Shimada, Hitoshi Nishimura.
      Most animals have male and female, whereas flowering plants are hermaphrodites. Exceptionally, a small population of invertebrates, including ascidians and nematodes, has hermaphrodite in reproductive strategies. Several ascidians exhibit strict self-sterility (or self-incompatibility), similar to flowering plants. Such a self-incompatibility mechanism in ascidian has been revealed to be very similar to those of flowering plants. Here, we describe the mechanisms of ascidian fertilization shared with invertebrates and mammals, as well as with plants. In the nematode Caenorhabditis elegans, having self-fertile hermaphrodite and male, several genes responsible for fertilization are homologous to those of mammals. Thus, novel proteins responsible for fertilization will be easily disclosed by the analyses of sterile mutants. In this review, we focus on the same or similar reproductive strategies by shedding lights on the common mechanisms of fertilization, particularly in hermaphrodites.
    Keywords:  Ascidian; Egg; Fertilization; Flowering plant; Hermaphrodite; Mouse; Nematode; Self-incompatibility; Sperm
    DOI:  https://doi.org/10.1016/bs.ctdb.2025.01.010
  16. Genetics. 2025 Apr 04. pii: iyae217. [Epub ahead of print]
    Origin and establishment of the germline in Drosophila melanogaster.
    Ruoyu Chen, Sherilyn Grill, Benjamin Lin, Mariyah Saiduddin, Ruth Lehmann.
      The continuity of a species depends on germ cells. Germ cells are different from all the other cell types of the body (somatic cells) as they are solely destined to develop into gametes (sperm or egg) to create the next generation. In this review, we will touch on 4 areas of embryonic germ cell development in Drosophila melanogaster: the assembly and function of germplasm, which houses the determinants for germ cell specification and fate and the mitochondria of the next generation; the process of pole cell formation, which will give rise to primordial germ cells (PGCs); the specification of pole cells toward the PGC fate; and finally, the migration of PGCs to the somatic gonadal precursors, where they, together with somatic gonadal precursors, form the embryonic testis and ovary.
    Keywords:  Nanos, Tudor, Vasa, Oskar; PGC migration; RNA localization; biomolecular condensates; germ cell; germ granules; germline; germplasm; gonad; mitochondria; pole cells; primordial germ cell
    DOI:  https://doi.org/10.1093/genetics/iyae217
  17. bioRxiv. 2025 Mar 16. pii: 2025.03.14.643309. [Epub ahead of print]
    TORC1-driven translation of Nucleoporin44A promotes chromatin remodeling and germ cell-to-maternal transition in Drosophila.
    Noor M Kotb, Gulay Ulukaya, Anupriya Ramamoorthy, Lina Seojin Park, Julia Tang, Dan Hasson, Prashanth Rangan.
      Oocyte specification is a critical developmental transition that requires the coordinated repression of germ cell-specific genes and activation of the maternal program to support embryogenesis. In Drosophila, the timely repression of germ cell and early oogenesis genes is essential for this transition, yet the mechanisms that coordinate this process remain unclear. Here, we uncover an unexpected translation-chromatin axis, where transient Target of Rapamycin Complex 1 (TORC1)-driven translation triggers chromatin remodeling, ensuring irreversible oocyte fate commitment. Through a screen, we identified ribosome biogenesis regulators, including Zinc finger protein RP-8 (Zfrp8) and TORC1 components, as key mediators of gene silencing. We show that TORC1 activity increases during oocyte specification, and disrupting ribosome biogenesis, translation, or TORC1 function prevents proper heterochromatin formation, leading to epigenetic instability. Polysome-seq analysis of zfrp8-depleted ovaries revealed that Zfrp8 is required for the translation of Nucleoporin 44A (Nup44A), a key nuclear pore complex (NPC) component. Given the role of the NPC in chromatin organization, independent disruption of Nup44A results in defective silencing of the germ cell and early oogenesis genes. Our findings reveal a mechanism in which translation-driven NPC remodeling coordinates heterochromatin establishment, facilitating the germ cell-to-maternal transition and ensuring proper oocyte fate commitment.
    Keywords:  Drosophila; Ribosome biogenesis; TORC1; Translation; chromatin; epigenetics; germ line; oocyte specification
    DOI:  https://doi.org/10.1101/2025.03.14.643309
  18. bioRxiv. 2025 Mar 17. pii: 2025.03.13.643173. [Epub ahead of print]
    Multiple domains of scaffold Tudor protein play non-redundant roles in Drosophila germline.
    Samuel J Tindell, Alyssa G Boeving, Julia Aebersold, Alexey L Arkov.
      Scaffold proteins play crucial roles in subcellular organization and function. In many organisms, proteins with multiple Tudor domains are required for the assembly of membraneless RNA-protein organelles (germ granules) in germ cells. Tudor domains are protein-protein interaction modules which bind to methylated polypeptides. Drosophila Tudor protein contains eleven Tudor domains, which is the highest number known in a single protein. The role of each of these domains in germ cell formation has not been systematically tested and it is not clear if some domains are functionally redundant. Using CRISPR methodology, we generated mutations in several uncharacterized Tudor domains and showed that they all caused defects in germ cell formation. Mutations in individual domains affected Tudor protein differently causing reduction in protein levels, defects in subcellular localization and in the assembly of germ granules. Our data suggest that multiple domains of Tudor protein are all needed for efficient germ cell formation highlighting the rational for keeping many Tudor domains in protein scaffolds of biomolecular condensates in Drosophila and other organisms.
    DOI:  https://doi.org/10.1101/2025.03.13.643173
  19. Cell Rep. 2025 Apr 03. pii: S2211-1247(25)00266-9. [Epub ahead of print]44(4): 115495
    Topoisomerase 3b facilitates piRNA biogenesis to promote transposon silencing and germ cell development.
    Seung Kyu Lee, Weiping Shen, William Wen, Yuyoung Joo, Yutong Xue, Aaron Park, Amy Qiang, Shuaikun Su, Tianyi Zhang, Megan Zhang, Jinshui Fan, Yongqing Zhang, Supriyo De, Ildar Gainetdinov, Alexei Sharov, Manolis Maragkakis, Weidong Wang.
      Topoisomerases typically function in the nucleus to relieve topological stress in DNA. Here, we show that a dual-activity topoisomerase, Top3b, and its partner, TDRD3, largely localize in the cytoplasm and interact biochemically and genetically with PIWI-interacting RNA (piRNA) processing enzymes to promote piRNA biogenesis, post-transcriptional gene silencing (PTGS) of transposons, and Drosophila germ cell development. Top3b requires its topoisomerase activity to promote PTGS of a transposon reporter and preferentially silences long and highly expressed transposons, suggesting that RNAs with these features may produce more topological stress for topoisomerases to solve. The double mutants between Top3b and piRNA processing enzymes exhibit stronger disruption of the signatures and levels of germline piRNAs, more de-silenced transposons, and larger defects in germ cells than either single mutant. Our data suggest that Top3b can act in an RNA-based process-piRNA biogenesis and PTGS of transposons-and this function is required for Top3b to promote normal germ cell function.
    Keywords:  Aub; CP: Developmental biology; CP: Molecular biology; Piwi; TDRD3; Top3b; fertility; germ cells; oogenesis; piRNA; topoisomerase; transposon
    DOI:  https://doi.org/10.1016/j.celrep.2025.115495
  20. bioRxiv. 2025 Mar 13. pii: 2025.03.10.642432. [Epub ahead of print]
    Fusome morphogenesis is sufficient to promote female germline stem cell self-renewal in Drosophila.
    Amanda M Powell, Anna E Williams, Elizabeth T Ables.
      Many tissue-resident stem cells are retained through asymmetric cell division, a process that ensures stem cell self-renewal through each mitotic cell cycle. Asymmetric organelle distribution has been proposed as a mechanism by which stem cells are marked for long-term retention; however, it is not clear whether biased organelle localization is a cause or an effect of asymmetric division. In Drosophila females, an endoplasmic reticulum-like organelle called the fusome is continually regenerated in germline stem cells (GSCs) and associated with GSC division. Here, we report that the β-importin Tnpo-SR is essential for fusome regeneration. Depletion of Tnpo-SR disrupts cytoskeletal organization during interphase and nuclear membrane remodeling during mitosis. Tnpo-SR does not localize to microtubules, centrosomes, or the fusome, suggesting that its role in maintaining these processes is indirect. Despite this, we find that restoring fusome morphogenesis in Tnpo-SR -depleted GSCs is sufficient to rescue GSC maintenance and cell cycle progression. We conclude that Tnpo-SR functionally fusome regeneration to cell cycle progression, supporting the model that asymmetric rebuilding of fusome promotes maintenance of GSC identity and niche retention.
    Summary Statement: Regeneration of the fusome, an ER-like organelle in Drosophila female germline stem cells, relies on Tnpo-SR-dependent reorganization of the microtubule network during interphase.
    DOI:  https://doi.org/10.1101/2025.03.10.642432
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