Division Of Meiosis Research Articles

Meiosis-specific functions of kinetochore protein SPC105R required for chromosome segregation in Drosophila oocytes.

The reductional division of meiosis I requires the separation of chromosome pairs towards opposite poles. We have previously implicated the outer kinetochore protein SPC105R/KNL1 in driving meiosis I chromosome segregation through lateral attachments to microtubules and coorientation of sister centromeres. To identify the domains of SPC105R that are critical for meiotic chromosome segregation, an RNAi-resistant gene expression system was developed. We found that the SPC105R C-terminal domain (aa 1284-1960) is necessary and sufficient for recruiting NDC80 to the kinetochore and building the outer kinetochore. Furthermore, the C-terminal domain recruits BUBR1, which in turn recruits the cohesion protection proteins MEI-S332 and PP2A. Of the remaining 1283 amino acids, we found the first 473 are most important for meiosis. The first 123 amino acids of the N-terminal half of SPC105R contain the conserved SLRK and RISF motifs that are targets of PP1 and Aurora B kinase and are most important for regulating the stability of microtubule attachments and maintaining metaphase I arrest. The region between amino acids 124 and 473 are required for lateral microtubule attachments and biorientation of homologues, which are critical for accurate chromosome segregation in meiosis I.

CYTOGENETIC EFFECTS OF SURFACTANTS

Introduction. The widespread use of surfactants in economic activity and life has led to global pollution. The negative impact of surfactants on various characteristics of living organisms has been revealed, which makes a research on the safety of surfactants extremely relevant. Aim. The aim of this work was to study the genotoxic potential of anionic and cationic surfactants. Methods. The influence of anionic (sodium stearate and alkylbenzenesulpho-acid) and cationic (Praepagen TQ) surfactants on the value of the mitotic index, as well as on the regularity of mitosis and meiosis of Triticum aestivum L. cv. Odesa fantasy by standard cytogenetic methods. Main results. Under the action of surfactants in the root meristem of sprouts, the mitotic index significantly decreased and the number of cells containing chromosomal aberrations increased. Among the abnormalities at the ana-telophase stage, cells with lagging chromosomes, fragments, the formation of chromosomal bridges, and complex disorders were observed. These changes were directly proportional to the concentration of the drugs. The action of the cationic drug was less harmful than the action of both anionic drugs. Treatment of plants with surfactants led to a highly reliable increase in the proportion of abnormal MCPs in both the first and second division of meiosis, directly proportional to the concentration of surfactants applied. No differences were found between the first and second meiotic divisions in terms of the frequency of formation of defective MCPs. Both anionic surfactants had a stronger effect than the cationic one; with the use of alkylbenzenesulfonic acid, the degree of violations in microsporocytes was the greatest. Conclusions. A significant decrease in the mitotic index and an increase in the proportion of cells containing chromosomal aberrations in the root meristem of sprouts, as well as a significant increase in the proportion of abnormal MCPs in both the first and second division of meiosis, were found to be directly proportional to the concentration of surfactant. According to all the parameters studied, the action of the cationic drug “Praepagen TQ” was milder than the action of both anionic surfactants.

The Use of Parthenogenetic Clones to Create Highly Heterogeneous Hybrids of the Silkworm (Bombyx mori L.)

Since the entire world's sericulture, to achieve maximum heterosis is based on the feeding of hybrids of only the first generation, therefore, operations for the preparation of pure hybrids are of particular importance. In Uzbekistan, the Sericulture Research Institute has developed new biotechnologies specifically to solve this problem, and genetically modified breeds and parthenogenetic clones have been created on their basis. The unfertilized eggs are thermally activated at t = 46°C for 18 minutes, and the reducing division of meiosis in the germ cells of the silkworm is hampered. As a result, the eggs remain with a diploid set of chromosomes and develop as zygotes. Since silkworm females are heterogamous by sex chromosomes, only female parthenogenetic clones develop from thermally activated eggs. Clonal-breed hybrids, characterized by increased viability of caterpillars – 93,5-98,0% (in the control – 90,0%), the high cocoon shell ratio – 22,1-23,8% (in the control – 22,5%), increased egg-bearing capacity - 622-639 pcs (in the control - 630 pcs), metric number of thread - 3344-4065 units (in the control - 3321), the synchronicity of caterpillar development, uniformity of cocoons, ease of preparation. The technology of thermal activation of unfertilized silkworm eggs for parthenogenetic development is not particularly difficult, therefore clones can reproduce the required number of generations and in an unlimited number of individuals. The second component for hybridization can be males of almost any breed. Clones, due to their genetic constancy, do not need breeding and breeding selection, they do not need to be divided by gender, because they are represented by only one female sex, and have high combinational ability and amicable development.

Bouquet Formation Failure in Meiosis of F1 Wheat-Rye Hybrids with Mitotic-Like Division.

Bouquet formation is believed to be involved in initiating homologous chromosome pairings in meiosis. A bouquet is also formed in the absence of chromosome pairing, such as in F1 wheat–rye hybrids. In some hybrids, meiosis is characterized by a single, mitotic-like division that leads to the formation of unreduced gametes. In this study, FISH with the telomere and centromere-specific probe, and immunoFISH with ASY1, CENH3 and rye subtelomere repeat pSc200 were employed to perform a comparative analysis of early meiotic prophase nuclei in four combinations of wheat–rye hybrids. One of these, with disomic rye chromosome 2R, is known to undergo normal meiosis, and here, 78.9% of the meiocytes formed a normal-appearing telomere bouquet and rye subtelomeres clustered in 83.2% of the meiocytes. In three combinations with disomic rye chromosomes 1R, 5R and 6R, known to undergo a single division of meiosis, telomeres clustered in 11.4%, 44.8% and 27.6% of the meiocytes, respectively. In hybrids with chromosome 1R, rye subtelomeres clustered in 12.19% of the meiocytes. In the remaining meiocytes, telomeres and subtelomeres were scattered along the nucleus circumference, forming large and small groups. We conclude that in wheat–rye hybrids with mitotic-like meiosis, chromosome behavior is altered already in the early prophase.

The Spo13/Meikin pathway confines the onset of gamete differentiation to meiosis II in yeast

Sexual reproduction requires genome haploidization by the two divisions of meiosis and a differentiation program to generate gametes. Here, we have investigated how sporulation, the yeast equivalent of gamete differentiation, is coordinated with progression through meiosis. Spore differentiation is initiated at metaphase II when a membrane‐nucleating structure, called the meiotic plaque, is assembled at the centrosome. While all components of this structure accumulate already at entry into meiosis I, they cannot assemble because centrosomes are occupied by Spc72, the receptor of the γ‐tubulin complex. Spc72 is removed from centrosomes by a pathway that depends on the polo‐like kinase Cdc5 and the meiosis‐specific kinase Ime2, which is unleashed by the degradation of Spo13/Meikin upon activation of the anaphase‐promoting complex at anaphase I. Meiotic plaques are finally assembled upon reactivation of Cdk1 at entry into metaphase II. This unblocking‐activation mechanism ensures that only single‐copy genomes are packaged into spores and might serve as a paradigm for the regulation of other meiosis II‐specific processes.

ПРЕИМУЩЕСТВА ИСПОЛЬЗОВАНИЯ ПАРТЕНОГЕНЕТИЧЕСКИХ КЛОНОВ ТУТОВОГО ШЕЛКОПРЯДА (BOMBYX MORI L.) В ГИБРИДИЗАЦИИ

The fierce competition in the global silk market encourages the development and application of new biotechnologies in sericulture, such as cloning. The term “clone” in Greek means “branch”. A clone is an offspring of a single organism propagated without fertilization. All cloned individuals are genetically identical and are copies of each other. Clones are obtained in different ways. In case of the silkworm, this is a parthenogenetic development, which is an unnatural way of reproduction for the silkworm. Thermoactivation of an unfertilized greene at t0=46 0C during 18, leads to inhibition of the reduction division of meiosis in the silkworm germ cells. As a result, the eggs remain with a diploid set of chromosomes and develop as zygotes. Since the female cells in the sex chromosomes of the silkworm are heterogametic, only female parthenogenetic clones develop from thermally activated eggs. This feature makes silkworm clones extremely attractive for creating 100% pure hybrids. As the sericulture globally is based on the production of hybrids of the first generation only, in order to use maximum heterosis, the accuracy of preparation of hybrids is becoming particularly important.

Микроспорогенез и образование пыльцы у лиственницы Сукачева (Larix Sukaczewii Djil.) на постоянном лесосеменном участке Семилукского лесопитомника

The formation of male and female generative buds in the Sukachev larch in the conditions of Voronezh in the second decade of August is considered. The behavior of chromosomes in the meta-, ana -, and telophase of the first and second divisions of meiosis is analyzed. In each phase, 150–200 microsporocytes were taken into account. According to the results of the conducted studies, it was revealed that the microsporogenesis of larch proceeded asynchronously. A significant proportion of the disorders are caused by chromosome lag and the formation of bridges, the formation of a hexad, and the release of chromosomes outside the division spindle. The viability of Sukachev larch pollen is estimated to be high. A small number of disturbances in the process of meiotic divisions and the formation of gametophytes did not lead to the formation of a significant amount of sterile pollen. The average pollen size varies between 82.18–86.4 microns. Pollen has a spherical shape

Phosphoregulation of HORMA domain protein HIM-3 promotes asymmetric synaptonemal complex disassembly in meiotic prophase in Caenorhabditis elegans.

In the two cell divisions of meiosis, diploid genomes are reduced into complementary haploid sets through the discrete, two-step removal of chromosome cohesion, a task carried out in most eukaryotes by protecting cohesion at the centromere until the second division. In eukaryotes without defined centromeres, however, alternative strategies have been innovated. The best-understood of these is found in the nematode Caenorhabditis elegans: after the single off-center crossover divides the chromosome into two segments, or arms, several chromosome-associated proteins or post-translational modifications become specifically partitioned to either the shorter or longer arm, where they promote the correct timing of cohesion loss through as-yet unknown mechanisms. Here, we investigate the meiotic axis HORMA-domain protein HIM-3 and show that it becomes phosphorylated at its C-terminus, within the conserved "closure motif" region bound by the related HORMA-domain proteins HTP-1 and HTP-2. Binding of HTP-2 is abrogated by phosphorylation of the closure motif in in vitro assays, strongly suggesting that in vivo phosphorylation of HIM-3 likely modulates the hierarchical structure of the chromosome axis. Phosphorylation of HIM-3 only occurs on synapsed chromosomes, and similarly to other previously-described phosphorylated proteins of the synaptonemal complex, becomes restricted to the short arm after designation of crossover sites. Regulation of HIM-3 phosphorylation status is required for timely disassembly of synaptonemal complex central elements from the long arm, and is also required for proper timing of HTP-1 and HTP-2 dissociation from the short arm. Phosphorylation of HIM-3 thus plays a role in establishing the identity of short and long arms, thereby contributing to the robustness of the two-step chromosome segregation.

Diploid Male Gametes Circumvent Hybrid Sterility Between Asian and African Rice Species.

In F1 hybrids of Oryza sativa (Asian rice) and Oryza glaberrima (African rice), heterozygosity leads to a complete gamete abortion because of allelic conflict at each of the 13 hybrid sterility (HS) loci. We systematically produced 19 plants from the F1 hybrids of both the rice species by the anther culture (AC) method. Five of the 19 interspecific hybrid plants were partially fertile and able to produce seeds. Unlike ordinal doubled haploid plants resulting from AC, these regenerated plants showed various ploidy levels (diploid to pentaploid) and different zygosities (completely homozygous, completely heterozygous, and a combination). These properties were attributable to meiotic anomalies in the interspecific hybrid F1 plants. Examination of the genetic structures of the regenerated plants suggested meiotic non-reduction took place in the interspecific hybrid F1 plants. The centromeric regions in the regenerated plants revealed that the abnormal first and/or second divisions of meiosis, namely the first division restitution (FDR) and/or second division restitution (SDR), had occurred in the interspecific hybrid. Immunohistochemical observations also verified these phenomena. FDR and SDR occurrences at meiosis might strongly lead to the formation of diploid microspores. The results demonstrated that meiotic anomalies functioned as a reproductive barrier occurred before the HS genes acted in gamete of the interspecific hybrid. Although such meiotic anomalies are detrimental to pollen development, the early rescue of microspores carrying the diploid gamete resulted in the fertile regenerated plants. The five partially fertile plants carrying tetraploid genomes with heterozygous alleles of the HS loci produced fertile diploid pollens, implying that the diploid gametes circumvented the allelic conflicts at the HS loci. We also proposed how diploid male gametes avoid HS with the killer–protector model.

Two auxiliary factors promote Dmc1-driven DNA strand exchange via stepwise mechanisms

Homologous recombination (HR) is a universal mechanism operating in somatic and germ-line cells, where it contributes to the maintenance of genome stability and ensures the faithful distribution of genetic material, respectively. The ability to identify and exchange the strands of two homologous DNA molecules lies at the heart of HR and is mediated by RecA-family recombinases. Dmc1 is a meiosis-specific RecA homolog in eukaryotes, playing a predominant role in meiotic HR. However, Dmc1 cannot function without its two major auxiliary factor complexes, Swi5-Sfr1 and Hop2-Mnd1. Through biochemical reconstitutions, we demonstrate that Swi5-Sfr1 and Hop2-Mnd1 make unique contributions to stimulate Dmc1-driven strand exchange in a synergistic manner. Mechanistically, Swi5-Sfr1 promotes establishment of the Dmc1 nucleoprotein filament, whereas Hop2-Mnd1 defines a critical, rate-limiting step in initiating strand exchange. Following execution of this function, we propose that Swi5-Sfr1 then promotes strand exchange with Hop2-Mnd1. Thus, our findings elucidate distinct yet complementary roles of two auxiliary factors in Dmc1-driven strand exchange, providing mechanistic insights into some of the most critical steps in meiotic HR.

The True Story of Yeti, the "Abominable" Heterochromatic Gene of Drosophila melanogaster.

The Drosophila Yeti gene (CG40218) was originally identified by recessive lethal mutation and subsequently mapped to the deep pericentromeric heterochromatin of chromosome 2. Functional studies have shown that Yeti encodes a 241 amino acid protein called YETI belonging to the evolutionarily conserved family of Bucentaur (BCNT) proteins and exhibiting a widespread distribution in animals and plants. Later studies have demonstrated that YETI protein: (i) is able to bind both subunits of the microtubule-based motor kinesin-I; (ii) is required for proper chromosome organization in both mitosis and meiosis divisions; and more recently (iii) is a new subunit of dTip60 chromatin remodeling complex. To date, other functions of YETI counterparts in chicken (CENtromere Protein 29, CENP-29), mouse (Cranio Protein 27, CP27), zebrafish and human (CranioFacial Development Protein 1, CFDP1) have been reported in literature, but the fully understanding of the multifaceted molecular function of this protein family remains still unclear. In this review we comprehensively highlight recent work and provide a more extensive hypothesis suggesting a broader range of YETI protein functions in different cellular processes.

Premeiotic and meiotic failures lead to hybrid male sterility in the Anopheles gambiae complex.

Hybrid male sterility (HMS) contributes to speciation by restricting gene flow between related taxa. Detailed cytological characterization of reproductive organs in hybrid males is important for identifying phenotypes that can help guide searches of speciation genes. To investigate possible cellular causes of HMS, we performed crosses between closely related species of the Anopheles gambiae complex: An. merus with An. gambiae or An. coluzzii. We demonstrate that HMS in African malaria mosquitoes involves two defects in the reciprocal crosses: a premeiotic arrest of germline stem cells in degenerate testes and a failure of the reductional meiotic division of primary spermatocytes in normal-like testes. The premeiotic arrest in degenerate testes of hybrids is accompanied by a strong suppression of meiotic and postmeiotic genes. Unlike pure species, sex chromosomes in normal-like testes of F1 hybrids are largely unpaired during meiotic prophase I and all chromosomes show various degrees of insufficient condensation. Instead of entering reductional division in meiosis I, primary spermatocytes prematurely undergo an equational mitotic division producing non-motile diploid sperm. Thus, our study identified cytogenetic errors in interspecies hybrids that arise during the early stages of postzygotic isolation.

Histology and ultrastructure of the testis and vas deferens in Pseudochorthippus parallelus parallelus (Orthoptera, Acrididae).

Pseudochorthippus parallelus parallelus (Zetterstedt, 1821) (Orthoptera, Acrididae) is a widespread species in Europe, and also it is localized in some regions in Turkey such as Bursa, Eskişehir, Ankara, Bolu, Düzce, and Çankırı. The features of the reproductive organs such as the numbers and shapes of testes and follicles can be used as taxonomical characters. For this purpose, the ultrastructural and histological features of testis and vas deferens in P. parallelus parallelus were examined with using light microscope, scanning electron microscope, and transmission electron microscope. The mature P. parallelus parallelus has two conjugated testes produce spermatozoa. Each testis is composed of numerous testis follicles in which different stages of spermatogenesis and spermiogenesis develop. First, spermatocytes are formed by the mitosis division of the germ cells at the distal end of the follicles. Then, spermatocytes form spermatids by meiosis division in the middle region of the follicles. Finally, spermatids are differentiated to spermatozoa at the proximal region of the follicles. After maturation of the spermatozoa, sperm tails come together as the sperm bundles called as spermatodesm. Each follicle is connected to vas deferens via vas efferens to discharging spermatozoa. In spite of some differences, the testes and the vas deferens in P. parallelus parallelus are highly similar to the those of other species, especially Orthopteran species.

Cloning in sturgeon hybrids (Acipenseridae): experimental reproduction of the first stages of reticular speciation in fish and the method of obtaining all-female offspring

Cloning in sturgeon hybrids (Acipenseridae): experimental reproduction of the first stages of reticular speciation in fish and the method of obtaining all-female offspring

Formation of ovarian reserve

The review of the literature is devoted to modern data on the formation of the ovarian reserve of the female sexual organ. The relationship between the size of the ovarian reserve and length of reproductive capacity emphasizes the importance of understanding the regulatory factors and processes that determine its creation. We described ovarian reserve markers and regulators such as oocyte phosphotidylinositol-3-kinase, a stem-cell factor (kit ligand) that promote the survival of follicles during neonatal development, synaptonemic complex (SCP3), which is the marker of the first division of meiosis, as well as genes DMC1 and PTEN, involved in meiotic transformations and recruitment of primordial follicles. Changes in the expression of some genes and factors in the human fetal ovaries during primary follicular assembly now give an idea of the ways controlling early folliculogenesis. Aberrant production of these factors can cause dysfunction, the development of ovarian disorders and a defective follicular reserve. In particular, the degree of change in the number of germ cells at each of the stages leading to the creation of an ovarian reserve should be noted. This change can affect the final size of the follicular stock, and, consequently, the reproductive longevity of a person and health in the postproductive period. In particular, the number of primary follicles during puberty is positively correlated with the number of growing follicles and their response to gonadotropin treatment. The size of the ovarian reserve depends on the genes involved in proliferation and differentiation of germ cells, sexual differentiation, meiosis, germ cell degeneration, the formation of primary follicles, and the potential mechanism for self-renewal of embryonic stem cells. For example, a possible molecular mechanism has been established leading to a meiotic process in oocytes involving the above genes and factors, as well as apoptotic and antiapoptical signals: Bax, Bcl-2, p53, CDK1, Lsd1, Notch, Stra8, Dazl, Dmc1, Rec8, XIAP , PUMA. Therefore, understanding all the subtleties and molecular mechanisms at each stage of laying down and developing the ovaries, sex cells and their environment, and the death of gametes, can help to search for possible regulators and prevent pathological depletion of the follicular stock.

Scraping the tip of Zip1's role in meiotic chromosome dynamics: Using lacO/LacI Corecruitment to identify crossover promoting factors that interface with the N‐terminus of a synaptonemal complex protein

During the first division of meiosis, diploid nuclei divide to produce nuclei with only one set of chromosomes. Accurate chromosome segregation during this so‐called “reductional” division relies on the prior establishment of recombination‐based associations between homologous chromosomes (homologs). Typically, homolog pairing and interhomolog recombination take place in conjunction with the assembly of a conserved tripartite chromosomal structure, the Synaptonemal Complex (SC), and interhomolog crossover recombination intermediates are processed within the physical context of SC. However, the molecular underpinnings of the relationship between SC and meiotic recombination remain obscure. The SC is assembled by rod‐like transverse filament proteins that bridge aligned homolog axes; transverse filaments interface with a central element substructure at the midline of the SC. In the yeast Saccharomyces cerevisiae, a major component of the SC transverse filament is the coiled‐coil protein, Zip1. Our prior work found that small, adjacent regions within Zip1's N terminus act to independently promote crossover recombination and SC assembly, and that versions of Zip1 missing residues 2–9 or 10–14 support SC assembly but not SC‐associated crossover formation. Mutants expressing zip1‐[Δ2–9] and zip1‐[Δ10–14] alleles assemble SC, but form remarkably large Zip1 polycomplex structures and display hyper‐SUMOylation of another SC protein, Ecm11, two relatively unusual meiotic phenotypes that are also observed in meiotic cells missing the crossover‐promoting factor, Zip3. These observations suggest that residues 2–14 of Zip1 somehow affect Zip3 behavior. Zip1 has previously been found to be essential for the recruitment of Zip3 protein to sites of recombination initiation on meiotic chromosomes, and chromatin immunoprecipitation experiments revealed that Zip3 fails to localize to all surveyed meiotic recombination initiation sites in zip1‐D1[Δ2–9] and zip1‐D2[Δ10–14] mutants, suggesting that the crossover defect exhibited by these mutants is based at least in part on the inability of the Zip1[Δ2–9] or Zip1[Δ10–14] proteins to recruit Zip3 to recombination initiation sites. Furthermore, cytological analysis indicated that Zip3 is excluded from the polycomplex structures assembled by Zip1‐[Δ2–9] or Zip1‐[Δ10–14] protein, suggesting that Zip1's residues 2–14 somehow interface with Zip3. I am currently creating a lacO/LacI co‐recruitment assay to investigate whether Zip1's N‐terminus is sufficient for recruiting Zip3 to an ectopic site in meiotic nucleus. I have created diploid strains in which the Zip1's N terminal residues 1–17, 1–33, 1–171, or 1–348 are fused to the N‐terminus of GFP‐LacI and that carry lacO on chromosome IV. Using immunofluorescence on surface spread meiotic chromosomes, I will ask whether Zip3‐MYC is recruited to a chimeric Zip1‐GFP‐LacI protein bound to a lacO array positioned on chromosome IV within the meiotic nucleus. The data from this experiment will not only provide strong evidence for a direct interaction between Zip1 and Zip3, but also establish a starting point for future structure‐function studies aimed at identifying residues that are critical for, and the meiotic genes that might regulate, a putative Zip1‐Zip3 interaction.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Monitoring Recombination During Meiosis in Budding Yeast.

Homologous recombination is fundamental to sexual reproduction, facilitating accurate segregation of homologous chromosomes at the first division of meiosis, and creating novel allele combinations that fuel evolution. Following initiation of meiotic recombination by programmed DNA double-strand breaks (DSBs), homologous pairing and DNA strand exchange form joint molecule (JM) intermediates that are ultimately resolved into crossover and noncrossover repair products. Physical monitoring of the DNA steps of meiotic recombination in Saccharomyces cerevisiae (budding yeast) cultures undergoing synchronous meiosis has provided seminal insights into the molecular basis of meiotic recombination and affords a powerful tool for dissecting the molecular roles of recombination factors. This chapter describes a suit of electrophoretic and Southern hybridization techniques used to detect and quantify the DNA intermediates of meiotic recombination at recombination hotspots in budding yeast. DSBs and recombination products (crossovers and noncrossovers) are resolved using one-dimensional electrophoresis and distinguished by restriction site polymorphisms between the parental chromosomes. Psoralen cross-linking is used to stabilize branched JMs, which are resolved from linear species by native/native two-dimensional electrophoresis. Native/denaturing two-dimensional electrophoresis is employed to determine the component DNA strands of JMs and to measure the processing of DSBs. These techniques are generally applicable to any locus where the frequency of recombination is high enough to detect intermediates by Southern hybridization.

Roles of Budding Yeast Hrr25 in Recombination and Sporulation.

Hrr25, a casein kinase 1 δ/ε homolog in budding yeast, is essential to set up mono-orientation of sister kinetochores during meiosis. Hrr25 kinase activity coordinates sister chromatid cohesion via cohesin phosphorylation. Here, we investigated the prophase role of Hrr25 using the auxin-inducible degron system and by ectopic expression of Hrr25 during yeast meiosis. Hrr25 mediates nuclear division in meiosis I but does not affect DNA replication. We also found that initiation of meiotic double-strand breaks as well as joint molecule formation were normal in HRR25-deficient cells. Thus, Hrr25 is essential for termination of meiotic division but not homologous recombination.

Kif4 Is Essential for Mouse Oocyte Meiosis.

Progression through the meiotic cell cycle must be strictly regulated in oocytes to generate viable embryos and offspring. During mitosis, the kinesin motor protein Kif4 is indispensable for chromosome condensation and separation, midzone formation and cytokinesis. Additionally, the bioactivity of Kif4 is dependent on phosphorylation via Aurora Kinase B and Cdk1, which regulate Kif4 function throughout mitosis. Here, we examine the role of Kif4 in mammalian oocyte meiosis. Kif4 localized in the cytoplasm throughout meiosis I and II, but was also observed to have a dynamic subcellular distribution, associating with both microtubules and kinetochores at different stages of development. Co-localization and proximity ligation assays revealed that the kinetochore proteins, CENP-C and Ndc80, are potential Kif4 interacting proteins. Functional analysis of Kif4 in oocytes via antisense knock-down demonstrated that this protein was not essential for meiosis I completion. However, Kif4 depleted oocytes displayed enlarged polar bodies and abnormal metaphase II spindles, indicating an essential role for this protein for correct asymmetric cell division in meiosis I. Further investigation of the phosphoregulation of meiotic Kif4 revealed that Aurora Kinase and Cdk activity is critical for Kif4 kinetochore localization and interaction with Ndc80 and CENP-C. Finally, Kif4 protein but not gene expression was found to be upregulated with age, suggesting a role for this protein in the decline of oocyte quality with age.

Meiotic Divisions: No Place for Gender Equality.

In multicellular organisms the fusion of two gametes with a haploid set of chromosomes leads to the formation of the zygote, the first cell of the embryo. Accurate execution of the meiotic cell division to generate a female and a male gamete is required for the generation of healthy offspring harboring the correct number of chromosomes. Unfortunately, meiosis is error prone. This has severe consequences for fertility and under certain circumstances, health of the offspring. In humans, female meiosis is extremely error prone. In this chapter we will compare male and female meiosis in humans to illustrate why and at which frequency errors occur, and describe how this affects pregnancy outcome and health of the individual. We will first introduce key notions of cell division in meiosis and how they differ from mitosis, followed by a detailed description of the events that are prone to errors during the meiotic divisions.