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Nature Plants Dec 2023The synaptonemal complex (SC) is a proteinaceous structure that forms between homologous chromosomes during meiosis prophase. The SC is widely conserved across species,...
The synaptonemal complex (SC) is a proteinaceous structure that forms between homologous chromosomes during meiosis prophase. The SC is widely conserved across species, but its structure and roles during meiotic recombination are still debated. While the SC central region is made up of transverse filaments and central element proteins in mammals and fungi, few central element proteins have been identified in other species. Here we report the identification of two coiled-coil proteins, SCEP1 and SCEP2, that form a complex and localize at the centre of the Arabidopsis thaliana SC. In scep1 and scep2 mutants, chromosomes are aligned but not synapsed (the ZYP1 transverse filament protein is not loaded), crossovers are increased compared with the wild type, interference is lost and heterochiasmy is strongly reduced. We thus report the identification of two plant SC central elements, and homologues of these are found in all major angiosperm clades.
Topics: Animals; Synaptonemal Complex; Prophase; Arabidopsis; Arabidopsis Proteins; Meiosis; Mammals
PubMed: 37973938
DOI: 10.1038/s41477-023-01558-y -
Biology of Reproduction Sep 2019Cyclins and cyclin-dependent kinases (CDKs) are key regulators of the cell cycle. Most of our understanding of their functions has been obtained from studies in... (Review)
Review
Cyclins and cyclin-dependent kinases (CDKs) are key regulators of the cell cycle. Most of our understanding of their functions has been obtained from studies in single-cell organisms and mitotically proliferating cultured cells. In mammals, there are more than 20 cyclins and 20 CDKs. Although genetic ablation studies in mice have shown that most of these factors are dispensable for viability and fertility, uncovering their functional redundancy, CCNA2, CCNB1, and CDK1 are essential for embryonic development. Cyclin/CDK complexes are known to regulate both mitotic and meiotic cell cycles. While some mechanisms are common to both types of cell divisions, meiosis has unique characteristics and requirements. During meiosis, DNA replication is followed by two successive rounds of cell division. In addition, mammalian germ cells experience a prolonged prophase I in males or a long period of arrest in prophase I in females. Therefore, cyclins and CDKs may have functions in meiosis distinct from their mitotic functions and indeed, meiosis-specific cyclins, CCNA1 and CCNB3, have been identified. Here, we describe recent advances in the field of cyclins and CDKs with a focus on meiosis and early embryogenesis.
Topics: Animals; Cyclin-Dependent Kinases; Cyclins; Embryo, Mammalian; Female; Gametogenesis; Germ Cells; Humans; Male; Mammals; Meiosis; Mice
PubMed: 31078132
DOI: 10.1093/biolre/ioz070 -
Frontiers in Cell and Developmental... 2023Meiosis is a specialized cell division that generates haploid gametes and is critical for successful sexual reproduction. During the extended meiotic prophase I,... (Review)
Review
Meiosis is a specialized cell division that generates haploid gametes and is critical for successful sexual reproduction. During the extended meiotic prophase I, homologous chromosomes progressively pair, synapse and desynapse. These chromosomal dynamics are tightly integrated with meiotic recombination (MR), during which programmed DNA double-strand breaks (DSBs) are formed and subsequently repaired. Consequently, parental chromosome arms reciprocally exchange, ultimately ensuring accurate homolog segregation and genetic diversity in the offspring. Surveillance mechanisms carefully monitor the MR and homologous chromosome synapsis during meiotic prophase I to avoid producing aberrant chromosomes and defective gametes. Errors in these critical processes would lead to aneuploidy and/or genetic instability. Studies of mutation in mouse models, coupled with advances in genomic technologies, lead us to more clearly understand how meiosis is controlled and how meiotic errors are linked to mammalian infertility. Here, we review the genetic regulations of these major meiotic events in mice and highlight our current understanding of their surveillance mechanisms. Furthermore, we summarize meiotic prophase genes, the mutations that activate the surveillance system leading to meiotic prophase arrest in mouse models, and their corresponding genetic variants identified in human infertile patients. Finally, we discuss their value for the diagnosis of causes of meiosis-based infertility in humans.
PubMed: 36910159
DOI: 10.3389/fcell.2023.1127440 -
Reproductive Sciences (Thousand Oaks,... Nov 2019Mechanisms of meiotic prophase I arrest maintenance (germinal vesicle [GV] stage) and meiotic resumption (germinal vesicle breakdown [GVBD] stage) in mammalian oocytes... (Review)
Review
Mechanisms of meiotic prophase I arrest maintenance (germinal vesicle [GV] stage) and meiotic resumption (germinal vesicle breakdown [GVBD] stage) in mammalian oocytes seem to be very complicated. These processes are regulated via multiple molecular cascades at transcriptional, translational, and posttranslational levels, and many of them are interrelated. There are many molecular cascades of meiosis maintaining and meiotic resumption in oocyte which are orchestrated by multiple molecules produced by pituitary gland and follicular cells. Furthermore, many of these molecular cascades are duplicated, thus ensuring the stability of the entire system. Understanding mechanisms of oocyte maturation is essential to assess the oocyte status, develop effective protocols of oocyte in vitro maturation, and design novel contraceptive drugs. Mechanisms of meiotic arrest maintenance at prophase I and meiotic resumption in mammalian oocytes are covered in the present article.
Topics: Animals; Cell Cycle Checkpoints; Female; Meiosis; Meiotic Prophase I; Oocytes; Oogenesis
PubMed: 29587616
DOI: 10.1177/1933719118765974 -
Frontiers in Cell and Developmental... 2021In female mammals, meiotic prophase one begins during fetal development. Oocytes transition through the prophase one substages consisting of leptotene, zygotene, and... (Review)
Review
In female mammals, meiotic prophase one begins during fetal development. Oocytes transition through the prophase one substages consisting of leptotene, zygotene, and pachytene, and are finally arrested at the diplotene substage, for months in mice and years in humans. After puberty, luteinizing hormone induces ovulation and meiotic resumption in a cohort of oocytes, driving the progression from meiotic prophase one to metaphase two. If fertilization occurs, the oocyte completes meiosis two followed by fusion with the sperm nucleus and preparation for zygotic divisions; otherwise, it is passed into the uterus and degenerates. Specifically in the mouse, oocytes enter meiosis at 13.5 days post coitum. As meiotic prophase one proceeds, chromosomes find their homologous partner, synapse, exchange genetic material between homologs and then begin to separate, remaining connected at recombination sites. At postnatal day 5, most of the oocytes have reached the late diplotene (or dictyate) substage of prophase one where they remain arrested until ovulation. This review focuses on events and mechanisms controlling the progression through meiotic prophase one, which include recombination, synapsis and control by signaling pathways. These events are prerequisites for proper chromosome segregation in meiotic divisions; and if they go awry, chromosomes mis-segregate resulting in aneuploidy. Therefore, elucidating the mechanisms regulating meiotic progression is important to provide a foundation for developing improved treatments of female infertility.
PubMed: 34095134
DOI: 10.3389/fcell.2021.667306 -
Cell Cycle (Georgetown, Tex.) Aug 2021A central player in meiotic chromosome dynamics is the conserved Polo-like kinase (PLK) family. PLKs are dynamically localized to distinct structures during meiotic... (Review)
Review
A central player in meiotic chromosome dynamics is the conserved Polo-like kinase (PLK) family. PLKs are dynamically localized to distinct structures during meiotic prophase and phosphorylate a diverse group of substrates to control homolog pairing, synapsis, and meiotic recombination. In a recent study, we uncovered the mechanisms that control the targeting of a meiosis-specific PLK-2 in . In early meiotic prophase, PLK-2 localizes to special chromosome regions known as pairing centers and drives homolog pairing and synapsis. PLK-2 then relocates to the synaptonemal complex (SC) after crossover designation and mediates chromosome remodeling required for homolog separation. What controls this intricate targeting of PLK-2 in space and time? We discuss recent findings and remaining questions for the future.
Topics: Animals; Binding Sites; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Chromosome Pairing; Chromosomes; Gene Expression Regulation; Meiosis; Meiotic Prophase I; Phosphorylation; Protein Binding; Protein Serine-Threonine Kinases; Signal Transduction
PubMed: 34266376
DOI: 10.1080/15384101.2021.1953232 -
Genes Nov 2021Regulation of transcriptional activity during meiosis depends on the interrelated processes of recombination and synapsis. In eutherian mammal spermatocytes,...
Regulation of transcriptional activity during meiosis depends on the interrelated processes of recombination and synapsis. In eutherian mammal spermatocytes, transcription levels change during prophase-I, being low at the onset of meiosis but highly increased from pachytene up to the end of diplotene. However, X and Y chromosomes, which usually present unsynapsed regions throughout prophase-I in male meiosis, undergo a specific pattern of transcriptional inactivation. The interdependence of synapsis and transcription has mainly been studied in mammals, basically in mouse, but our knowledge in other unrelated phylogenetically species is more limited. To gain new insights on this issue, here we analyzed the relationship between synapsis and transcription in spermatocytes of the grasshopper . Autosomal chromosomes of this species achieve complete synapsis; however, the single X sex chromosome remains always unsynapsed and behaves as a univalent. We studied transcription in meiosis by immunolabeling with RNA polymerase II phosphorylated at serine 2 and found that whereas autosomes are active from leptotene up to diakinesis, the X chromosome is inactive throughout meiosis. This inactivation is accompanied by the accumulation of, at least, two repressive epigenetic modifications: H3 methylated at lysine 9 and H2AX phosphorylated at serine 139. Furthermore, we identified that X chromosome inactivation occurs in premeiotic spermatogonia. Overall, our results indicate: (i) transcription regulation in spermatogenesis differs from the canonical pattern found in mammals and (ii) X chromosome inactivation is likely preceded by a process of heterochromatinization before the initiation of meiosis.
Topics: Animals; Chromosome Pairing; Epigenesis, Genetic; Female; Gene Silencing; Grasshoppers; Histones; Lysine; Male; Meiosis; Meiotic Prophase I; RNA Polymerase II; Spermatocytes; Spermatogenesis; X Chromosome; X Chromosome Inactivation; Y Chromosome
PubMed: 34946793
DOI: 10.3390/genes12121844 -
Asian Journal of Andrology 2021The synaptonemal complex (SC) is a meiosis-specific proteinaceous macromolecular structure that assembles between paired homologous chromosomes during meiosis in various... (Review)
Review
The synaptonemal complex (SC) is a meiosis-specific proteinaceous macromolecular structure that assembles between paired homologous chromosomes during meiosis in various eukaryotes. The SC has a highly conserved ultrastructure and plays critical roles in controlling multiple steps in meiotic recombination and crossover formation, ensuring accurate meiotic chromosome segregation. Recent studies in different organisms, facilitated by advances in super-resolution microscopy, have provided insights into the macromolecular structure of the SC, including the internal organization of the meiotic chromosome axis and SC central region, the regulatory pathways that control SC assembly and dynamics, and the biological functions exerted by the SC and its substructures. This review summarizes recent discoveries about how the SC is organized and regulated that help to explain the biological functions associated with this meiosis-specific structure.
Topics: Animals; Chromosome Segregation; Meiosis; Synaptonemal Complex
PubMed: 34528517
DOI: 10.4103/aja202153 -
Cell Cycle (Georgetown, Tex.) 2022Mammalian oocytes undergo two rounds of developmental arrest during maturation: at the diplotene of the first meiotic prophase and metaphase of the second meiosis. These... (Review)
Review
Mammalian oocytes undergo two rounds of developmental arrest during maturation: at the diplotene of the first meiotic prophase and metaphase of the second meiosis. These arrests are strictly regulated by follicular cells temporally producing the secondary messengers, cAMP and cGMP, and other factors to regulate maturation promoting factor (composed of cyclin B1 and cyclin-dependent kinase 1) levels in the oocytes. Out of these normally appearing developmental arrests, permanent arrests may occur in the oocytes at germinal vesicle (GV), metaphase I (MI), or metaphase II (MII) stage. This issue may arise from absence or altered expression of the oocyte-related genes playing key roles in nuclear and cytoplasmic maturation. Additionally, the assisted reproductive technology (ART) applications such as ovarian stimulation and culture conditions both of which harbor various types of chemical agents may contribute to forming the permanent arrests. In this review, the molecular determinants of developmental and permanent arrests occurring in the mammalian oocytes are comprehensively evaluated in the light of current knowledge. As number of permanently arrested oocytes at different stages is increasing in ART centers, potential approaches for inducing permanent arrests to obtain competent oocytes are discussed.
Topics: Animals; Mammals; Meiosis; Meiotic Prophase I; Metaphase; Oocytes
PubMed: 35072590
DOI: 10.1080/15384101.2022.2026704 -
ELife Oct 2023In sexually reproducing organisms, germ cells faithfully transmit the genome to the next generation by forming haploid gametes, such as eggs and sperm. Although most...
In sexually reproducing organisms, germ cells faithfully transmit the genome to the next generation by forming haploid gametes, such as eggs and sperm. Although most meiotic proteins are conserved between eggs and sperm, many aspects of meiosis are sexually dimorphic, including the regulation of recombination. The synaptonemal complex (SC), a large ladder-like structure that forms between homologous chromosomes, is essential for regulating meiotic chromosome organization and promoting recombination. To assess whether sex-specific differences in the SC underpin sexually dimorphic aspects of meiosis, we examined SC central region proteins (known as SYP proteins) in oogenesis and spermatogenesis and uncovered sex-specific roles for the SYPs in regulating meiotic recombination. We find that SC composition, specifically SYP-2, SYP-3, SYP-5, and SYP-6, is regulated by sex-specific mechanisms throughout meiotic prophase I. During pachytene, both oocytes and spermatocytes differentially regulate the stability of SYP-2 and SYP-3 within an assembled SC. Further, we uncover that the relative amount of SYP-2 and SYP-3 within the SC is independently regulated in both a sex-specific and a recombination-dependent manner. Specifically, we find that SYP-2 regulates the early steps of recombination in both sexes, while SYP-3 controls the timing and positioning of crossover recombination events across the genomic landscape in only oocytes. Finally, we find that SYP-2 and SYP-3 dosage can influence the composition of the other SYPs in the SC via sex-specific mechanisms during pachytene. Taken together, we demonstrate dosage-dependent regulation of individual SC components with sex-specific functions in recombination. These sexual dimorphic features of the SC provide insights into how spermatogenesis and oogenesis adapted similar chromosome structures to differentially regulate and execute recombination.
Topics: Animals; Female; Male; Caenorhabditis elegans; Synaptonemal Complex; Meiosis; Semen; Caenorhabditis elegans Proteins
PubMed: 37796106
DOI: 10.7554/eLife.84538