-
Cellular and Molecular Life Sciences :... Apr 2009Meiosis is a key cellular and molecular process for sexual reproduction contributing to the genetic variability of organisms. This process takes place after DNA... (Review)
Review
Meiosis is a key cellular and molecular process for sexual reproduction contributing to the genetic variability of organisms. This process takes place after DNA replication and consists in a double cellular division, giving rise to four haploid daughter cells or gametes. Meiotic recombination between homologous chromosomes, in the meiotic prophase I, is mediated by a tripartite structure named Synaptonemal Complex (SC). The SC is a peptidic scaffold in which the chromatin of homologous chromosomes is organized during the pachytene stage, holding chromosomes together until the meiotic recombination and genetic exchange have taken place. The role of chromatin structure in formation of the SC and the meiotic recombination at meiotic prophase I remain largely unknown. In this review we address the epigenome contribution to the SC formation at meiotic prophase I, with particular attention on the chromatin structure modifications occurring during the sub-stages of meiotic prophase I.
Topics: Animals; Chromatin; Chromosomes; DNA Methylation; DNA Replication; Epigenesis, Genetic; Meiosis; Meiotic Prophase I; Recombination, Genetic; Synaptonemal Complex
PubMed: 19099188
DOI: 10.1007/s00018-008-8584-2 -
Molecular Biology of the Cell Apr 2013During meiosis, evolutionarily conserved mechanisms regulate chromosome remodeling, leading to the formation of a tight bivalent structure. This bivalent, a linked pair...
During meiosis, evolutionarily conserved mechanisms regulate chromosome remodeling, leading to the formation of a tight bivalent structure. This bivalent, a linked pair of homologous chromosomes, is essential for proper chromosome segregation in meiosis. The formation of a tight bivalent involves chromosome condensation and restructuring around the crossover. The synaptonemal complex (SC), which mediates homologous chromosome association before crossover formation, disassembles concurrently with increased condensation during bivalent remodeling. Both chromosome condensation and SC disassembly are likely critical steps in acquiring functional bivalent structure. The mechanisms controlling SC disassembly, however, remain unclear. Here we identify akir-1 as a gene involved in key events of meiotic prophase I in Caenorhabditis elegans. AKIR-1 is a protein conserved among metazoans that lacks any previously known function in meiosis. We show that akir-1 mutants exhibit severe meiotic defects in late prophase I, including improper disassembly of the SC and aberrant chromosome condensation, independently of the condensin complexes. These late-prophase defects then lead to aberrant reconfiguring of the bivalent. The meiotic divisions are delayed in akir-1 mutants and are accompanied by lagging chromosomes. Our analysis therefore provides evidence for an important role of proper SC disassembly in configuring a functional bivalent structure.
Topics: Alleles; Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Cell Cycle Proteins; Chromosomal Proteins, Non-Histone; Chromosome Pairing; Chromosomes; Crossing Over, Genetic; Female; In Situ Hybridization, Fluorescence; Luminescent Proteins; Male; Meiotic Prophase I; Microscopy, Fluorescence; Mutation; Nuclear Proteins; Oocytes; RNA Interference; Rad51 Recombinase; Synaptonemal Complex; Time-Lapse Imaging
PubMed: 23363597
DOI: 10.1091/mbc.E12-11-0841 -
Sexual Development : Genetics,... 2022Germ cells are critical for the survival of our species. They are the only cells that undergo meiosis - the reductive form of cell division that is necessary for genetic... (Review)
Review
BACKGROUND
Germ cells are critical for the survival of our species. They are the only cells that undergo meiosis - the reductive form of cell division that is necessary for genetic reassortment of chromosomes and production of the haploid gametes, the sperm and eggs. Remarkably, the initial female/male fate decision in fetal germ cells does not depend on whether they are chromosomally XX or XY; rather, initial sexual fate is imposed by influences from the surrounding tissue. In mammals, the female germline is particularly precious: despite recent suggestions that germline stem cells exist in the ovary, it is still generally accepted that the ovarian reserve is finite, and its size is dependant on germ cells of the fetal ovary initiating meiosis in a timely manner.
SUMMARY
Prior to 2006, evidence suggested that gonadal germ cells initiate meiotic prophase I by default, but more recent data support a key role for the signalling molecule retinoic acid (RA) in instructing female germ cell fate. Newer findings also support a key meiosis-inducing role for another signalling molecule, bone morphogenic protein (BMP). Nonetheless, many questions remain.
KEY MESSAGES
Here, we review knowledge thus far regarding extrinsic and intrinsic determinants of a female germ cell fate, focusing on the mouse model.
PubMed: 35320803
DOI: 10.1159/000523763 -
Cell Cycle (Georgetown, Tex.) 2017
Topics: Animals; Meiosis; Meiotic Prophase I; Oocytes; Protein Serine-Threonine Kinases; Xenopus Proteins; Xenopus laevis
PubMed: 28750170
DOI: 10.1080/15384101.2017.1348069 -
Journal of Cell Science Jul 2008Sister-chromatid cohesion is essential for accurate chromosome segregation. A key discovery towards our understanding of sister-chromatid cohesion was made 10 years ago... (Review)
Review
Sister-chromatid cohesion is essential for accurate chromosome segregation. A key discovery towards our understanding of sister-chromatid cohesion was made 10 years ago with the identification of cohesins. Since then, cohesins have been shown to be involved in cohesion in numerous organisms, from yeast to mammals. Studies of the composition, regulation and structure of the cohesin complex led to a model in which cohesin loading during S-phase establishes cohesion, and cohesin cleavage at the onset of anaphase allows sister-chromatid separation. However, recent studies have revealed activities that provide cohesion in the absence of cohesin. Here we review these advances and propose an integrative model in which chromatid cohesion is a result of the combined activities of multiple cohesion mechanisms.
Topics: Animals; Cell Cycle Proteins; Chromosomal Proteins, Non-Histone; Chromosome Segregation; Chromosomes; DNA Replication; Humans; Meiosis; Meiotic Prophase I; Models, Genetic; Origin Recognition Complex; S Phase; Saccharomyces cerevisiae; Sister Chromatid Exchange; Cohesins
PubMed: 18565823
DOI: 10.1242/jcs.029132 -
Nature Communications May 2021Chromosomes pair and synapse with their homologous partners to segregate correctly at the first meiotic division. Association of telomeres with the LINC (Linker of...
Chromosomes pair and synapse with their homologous partners to segregate correctly at the first meiotic division. Association of telomeres with the LINC (Linker of Nucleoskeleton and Cytoskeleton) complex composed of SUN1 and KASH5 enables telomere-led chromosome movements and telomere bouquet formation, facilitating precise pairwise alignment of homologs. Here, we identify a direct interaction between SUN1 and Speedy A (SPDYA) and determine the crystal structure of human SUN1-SPDYA-CDK2 ternary complex. Analysis of meiosis prophase I process in SPDYA-binding-deficient SUN1 mutant mice reveals that the SUN1-SPDYA interaction is required for the telomere-LINC complex connection and the assembly of a ring-shaped telomere supramolecular architecture at the nuclear envelope, which is critical for efficient homologous pairing and synapsis. Overall, our results provide structural insights into meiotic telomere structure that is essential for meiotic prophase I progression.
Topics: Animals; Cell Cycle Proteins; Cell Line, Tumor; Crystallography, X-Ray; Cyclin-Dependent Kinase 2; Female; HEK293 Cells; Humans; Male; Meiotic Prophase I; Membrane Proteins; Mice; Mice, Transgenic; Microtubule-Associated Proteins; Mutation; Nuclear Proteins; Recombinant Proteins; Telomere
PubMed: 34039995
DOI: 10.1038/s41467-021-23550-w -
Cell Reports Jul 2017The meiotic functions of Emi2, an inhibitor of the APC/C complex, have been best characterized in oocytes where it mediates metaphase II arrest as a component of the...
The meiotic functions of Emi2, an inhibitor of the APC/C complex, have been best characterized in oocytes where it mediates metaphase II arrest as a component of the cytostatic factor. We generated knockout mice to determine the in vivo functions of Emi2-in particular, its functions in the testis, where Emi2 is expressed at high levels. Male and female Emi2 knockout mice are viable but sterile, indicating that Emi2 is essential for meiosis but dispensable for embryonic development and mitotic cell divisions. We found that, besides regulating cell-cycle arrest in mouse eggs, Emi2 is essential for meiosis I progression in spermatocytes. In the absence of Emi2, spermatocytes arrest in early diplotene of prophase I. This arrest is associated with decreased Cdk1 activity and was partially rescued by a knockin mouse model of elevated Cdk1 activity. Additionally, we detected expression of Emi2 in spermatids and sperm, suggesting potential post-meiotic functions for Emi2.
Topics: Animals; F-Box Proteins; Female; Gene Expression Regulation; Male; Meiotic Prophase I; Mice; Mice, Knockout; Spermatids; Spermatocytes; Spermatogenesis
PubMed: 28723571
DOI: 10.1016/j.celrep.2017.06.033 -
Molecular Biology of the Cell Dec 2020Androgen receptor (AR) signaling in Sertoli cells is known to be important for germ-cell progression through meiosis, but the extent to which androgens indirectly...
Androgen receptor (AR) signaling in Sertoli cells is known to be important for germ-cell progression through meiosis, but the extent to which androgens indirectly regulate specific meiotic stages is not known. Here, we combine synchronization of spermatogenesis, cytological analyses and single-cell RNAseq (scRNAseq) in the ertoli-ell ndrogen eceptor nockut (SCARKO) mutant and control mice, and demonstrate that SCARKO mutant spermatocytes exhibited normal expression and localization of key protein markers of meiotic prophase events, indicating that initiation of meiotic prophase is not androgen dependent. However, spermatocytes from SCARKO testes failed to acquire competence for the meiotic division phase. ScRNAseq analysis of wild-type and SCARKO mutant testes revealed a molecular transcriptomic block in an early meiotic prophase state (leptotene/zygotene) in mutant germ cells, and identified several misregulated genes in SCARKO Sertoli cells, many of which have been previously implicated in male infertility. Together, our coordinated cytological and scRNAseq analyses identified germ-cell intrinsic and extrinsic genes responsive to Sertoli-cell androgen signaling that promotes cellular states permissive for the meiotic division phase.
Topics: Androgens; Animals; Male; Meiosis; Meiotic Prophase I; Mice; Mice, Inbred C57BL; Mice, Knockout; Prophase; Receptors, Androgen; Sequence Analysis, RNA; Sertoli Cells; Signal Transduction; Single-Cell Analysis; Spermatocytes; Spermatogenesis; Testis
PubMed: 33026960
DOI: 10.1091/mbc.E20-05-0334 -
Frontiers in Plant Science 2017Meiosis is crucial in reproduction of plants and ensuring genetic diversity. Although several genes involved in homologous recombination and DNA repair have been...
Meiosis is crucial in reproduction of plants and ensuring genetic diversity. Although several genes involved in homologous recombination and DNA repair have been reported, their functions in rice () male meiosis remain poorly understood. Here, we isolated and characterized the rice () gene, encoding a conserved AAA-ATPase, and explored its function and importance in male meiosis and pollen formation. The rice mutant exhibited normal vegetative growth, but failed to produce seeds and displayed pollen abortion phenotype. Phenotypic comparisons between the wild-type and mutant demonstrated that OsFIGNL1 is required for anther development, and that the recessive mutation of this gene causes male sterility in rice. Complementation and CRISPR/Cas9 experiments demonstrated that wild-type is responsible for the male sterility phenotype. Subcellular localization showed that OsFIGNL1-green fluorescent protein was exclusively localized in the nucleus of rice protoplasts. Male meiosis in the mutant exhibited abnormal chromosome behavior, including chromosome bridges and multivalent chromosomes at diakinesis, lagging chromosomes, and chromosome fragments during meiosis. Yeast two-hybrid assays demonstrated OsFIGNL1 could interact with RAD51A1, RAD51A2, DMC1A, DMC1B, and these physical interactions were further confirmed by BiFC assay. Taken together, our results suggest that plays an important role in regulation of male meiosis and anther development.
PubMed: 29021797
DOI: 10.3389/fpls.2017.01639 -
PLoS Biology Dec 2011During mammalian meiosis, double-strand breaks are deliberately made throughout the genome and then repaired, leading to the exchange of genetic material between copies... (Review)
Review
During mammalian meiosis, double-strand breaks are deliberately made throughout the genome and then repaired, leading to the exchange of genetic material between copies of chromosomes. How the locations of breaks are specified was largely unknown until a fortuitous confluence of statistical genetics and molecular biology uncovered the role of PRDM9, a DNA binding protein. Many properties of this protein remain mysterious, however, including how it binds to DNA, how it contributes to male infertility-both in humans, and in hybrid mice-and why, in spite of its fundamental function in meiosis, its binding domain varies extensively among humans and across mammals. We present a brief summary of what has recently been learned about PRDM9 in different fields, focusing on the puzzles yet to be resolved.
Topics: Animals; Evolution, Molecular; Genetic Variation; Histone-Lysine N-Methyltransferase; Humans; Meiotic Prophase I; Polymorphism, Genetic; Recombination, Genetic; Zinc Fingers
PubMed: 22162947
DOI: 10.1371/journal.pbio.1001211