Kif11-haploinsufficient oocytes reveal spatially differential requirements for chromosome biorientation in the spindle
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ABSTRACT:
PROVIDER: PRJNA1198919 | ENA |
REPOSITORIES: ENA
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Project description:Bipolar spindle assembly and chromosome biorientation are prerequisites for chromosome segregation during cell division. The kinesin motor KIF11 (also widely known as Eg5) drives spindle bipolarization by sliding antiparallel microtubules bidirectionally, elongating a spherical spindle into a bipolar-shaped structure in acentrosomal oocytes. During meiosis I, this process stretches homologous chromosome pairs, establishing chromosome biorientation at the spindle equator. The quantitative requirement for KIF11 in acentrosomal spindle bipolarization and homologous chromosome biorientation remains unclear. Here, using a genetic strategy to modulate KIF11 expression levels, we show that Kif11 haploinsufficiency impairs spindle elongation, leading to the formation of a partially bipolarized spindle during meiosis I in mouse oocytes. While the partially bipolarized spindle allows chromosome stretching in the inner region of its equator, it fails to do so in the outer region, where merotelic kinetochore-microtubule attachments are favored to form. These findings demonstrate the necessity of biallelic functional Kif11 for bipolar spindle assembly in acentrosomal oocytes and reveal a spatially differential requirement for homologous chromosome biorientation within the spindle.
2025-07-01 | GSE284383 | GEO
Project description:The oocytes of many species, both invertebrate and vertebrate, contain a large collection of localized determinants in the form of proteins and translationally inactive maternal mRNAs. However, it is unknown whether mouse oocytes contain localized MmRNA determinants and what mechanisms might be responsible for their control. We collected intact MII oocytes, enucleated MII oocyte cytoplasts (with the spindle removed), and spindle-chromosome complexes which had been microsurgically removed. RNA was extracted, amplified, labeled, and applied to microarrays to determine if any MmRNA determinants were localized to the SCC. We used microarrays to determine whether maternal mRNAs in mouse oocytes are enriched in the meiotic spindle
2013-11-06 | E-GEOD-46875 | biostudies-arrayexpress
Project description:The oocytes of many species, both invertebrate and vertebrate, contain a large collection of localized determinants in the form of proteins and translationally inactive maternal mRNAs. However, it is unknown whether mouse oocytes contain localized MmRNA determinants and what mechanisms might be responsible for their control. We collected intact MII oocytes, enucleated MII oocyte cytoplasts (with the spindle removed), and spindle-chromosome complexes which had been microsurgically removed. RNA was extracted, amplified, labeled, and applied to microarrays to determine if any MmRNA determinants were localized to the SCC.
2013-11-06 | GSE46875 | GEO
Project description:The meiotic spindle in oocytes is formed without centrosomes. How a bipolar spindle is assembled and maintained around chromosomes in oocytes remains to be established. Multiple kinases are known to regulate the meiotic spindle, but how they execute their function is poorly understood. We found that the phospho-docking protein 14-3-3ε, together with the other isoform ζ, stabilises spindle bipolarity in Drosophila oocytes. A critical 14-3-3 target is the minus-end directed motor Ncd (human HSET; kinesin-14) which has well documented roles in stabilising a bipolar spindle in oocytes. Phospho-docking by 14-3-3 inhibits the microtubule binding activity of the non-motor Ncd tail. Further phosphorylation by Aurora B kinase can release Ncd from this inhibitory effect of 14-3-3. As Aurora B localises to chromosomes and spindles, 14-3-3 facilitates specific association of Ncd with spindle microtubules by preventing Ncd from binding to non-spindle microtubules in oocytes. Therefore, 14-3-3 translates a spatial cue provided by Aurora B to target Ncd selectively to the spindle within the large volume of oocytes.
2017-08-29 | PXD006080 | Pride
Project description:Oocytes develop the competence for meiosis and early embryogenesis during their growth. Setdb1 is a histone H3 lysine 9 (H3K9) methyltransferase required for post-implantation development and has been implicated in the transcriptional silencing of genes and endogenous retroviral elements (ERVs). To address its role in oogenesis and pre-implantation development, we conditionally deleted Setdb1 in growing oocytes. Loss of Setdb1 expression greatly impaired meiosis. It delayed meiotic resumption, altered the dynamics of chromatin condensation, and impaired kinetochore-spindle interactions, bipolar spindle organization, and chromosome segregation in more mature oocytes. The observed phenotypes related to changes in abundance of specific transcripts in mutant oocytes. Setdb1 maternally deficient embryos arrested during pre-implantation development and showed comparable defects during cell cycle progression and in chromosome segregation. Finally, transcriptional profiling data indicate that Setdb1 down-regulates rather than silences expression of ERVK and ERVL-MaLR retrotransposons and associated chimearic transcripts during oogenesis. Our results identify Setdb1 as a novel meiotic and embryonic competence factor in meiosis and mitosis, safeguarding genome integrity at the onset of life. We performed expression profiling on pools of 16 denuded GV-oocytes isolated per mouse. We used oocytes from 4 Setdb1 f/+; Zp3-cre mice and 2 Setdb1 f/- mice as controls and oocytes from 4 Setdb1 f/-; Zp3-cre mice as mutant.
2016-06-27 | E-GEOD-82002 | biostudies-arrayexpress
Project description:Oocyte quality largely determines the embryo development after fertilization. High-quality oocyte requires the competence of both cytoplasm and nucleus. However, clinically, the treatment of developmentally competent oocytes was limited. Here, in order to improve the embryo development efficiency of developmentally incompetent oocytes, we performed spindle-chromosome complex (SCC) transfer between in vitro matured (IVM) and in vivo matured (IVO) oocytes of the non-human primate. We observed that the blastocyst rate of embryos derived by transferring the SCC of IVM (IVM-SCC) oocytes into enucleated IVO oocytes was comparable with that of embryos derived by IVO oocytes. After transferring the reconstructed embryos into the uterus of surrogate mothers, two live rhesus monkeys were obtained, indicating that the nuclei of IVM oocytes support both the pre-and post-implantation embryo development of non-human primates.
2023-07-15 | GSE233232 | GEO
Project description:Chromosome aneuploidy increases in oocytes with maternal age, and is considered the leading cause for the increased incidence of infertility, miscarriage, and birth defects. Using mRNA-Sequencing of oocytes from 12 month old mouse versus 3 month young mouse, we identified a spindle assembly checkpoint gene, BubR1, whose expression was significantly decreased. We employed a mRNA microinjection based approach to increase BubR1 expression in aging oocytes. We find that increased expression of BubR1 protects against aneuploidy and chromosome misalignment in aging oocytes. After in vitro fertilization, the embryos derived from BubR1 increased expression aging oocytes exhibited chromosome stability as robust as those of the young ones. Furthermore, following embryo transfer, these embryos showed greatly improved developmental competency, with comparable levels of full-term development to those of the young ones. These results indicate that the decline in oocyte quality may be reversible and could lead to treatments that prolong female fertility. Examination of the effect of maternal aging on the mRNA expression in the mature oocytes of the female mice. Naturally ovulated mature oocytes (MII stage) were collected from 6 young (3 month) and 6 aging (12 month) female mice (3 oocytes per mice, 18 oocytes for each group).
2014-05-10 | E-GEOD-57482 | biostudies-arrayexpress
Project description:Oocytes develop the competence for meiosis and early embryogenesis during their growth. Setdb1 is a histone H3 lysine 9 (H3K9) methyltransferase required for post-implantation development and has been implicated in the transcriptional silencing of genes and endogenous retroviral elements (ERVs). To address its role in oogenesis and pre-implantation development, we conditionally deleted Setdb1 in growing oocytes. Loss of Setdb1 expression greatly impaired meiosis. It delayed meiotic resumption, altered the dynamics of chromatin condensation, and impaired kinetochore-spindle interactions, bipolar spindle organization, and chromosome segregation in more mature oocytes. The observed phenotypes related to changes in abundance of specific transcripts in mutant oocytes. Setdb1 maternally deficient embryos arrested during pre-implantation development and showed comparable defects during cell cycle progression and in chromosome segregation. Finally, transcriptional profiling data indicate that Setdb1 down-regulates rather than silences expression of ERVK and ERVL-MaLR retrotransposons and associated chimearic transcripts during oogenesis. Our results identify Setdb1 as a novel meiotic and embryonic competence factor in meiosis and mitosis, safeguarding genome integrity at the onset of life.
2016-06-27 | GSE82002 | GEO
Project description:Oocyte quality, which is directly related to reprogramming competence, is a major important limiting factor in animal cloning efficiency. Compared with oocytes matured in vivo, in vitro matured (IVM) oocytes exhibit lower oocyte quality and reprogramming competence primarily because of their higher levels of reactive oxygen species (ROS). In this study, we investigate whether supplementing the oocyte maturation medium with melatonin, a free radical scavenger, could improve oocyte quality and reprogramming competence. We found that 10−9 M melatonin effectively alleviated oxidative stress, markedly decreased early apoptosis levels, recovered the integrity of mitochondria, ameliorated the spindle assembly and chromosome alignment in oocytes, and significantly promoted subsequent cloned embryo development in vitro. We also analyzed the effects of melatonin on epigenetic modifications in bovine oocytes. Melatonin increased the global H3K9 acetylation levels, reduced the H3K9 methylation levels, and minimally affected DNA methylation and hydroxymethylation. Genome-wide expression analysis of genes affected by melatonin during oocyte maturation was conducted by high-throughput scRNA sequencing. We found that several important genes altered by melatonin were involved in oocyte stress defense. These genes included GSTP1, mitochondrial DNA polymerase POLG, mitochondrial ATP synthase ATP5E, centriole-enriched gene CEP295, spindle assembly-related gene TCTP, cytoprotection, and anti-apoptosis-related gene HSP27. Our results indicated critical roles of melatonin during bovine oocyte maturation and development.
2018-11-21 | GSE122738 | GEO
Project description:RNA sequencing of E10.5 neocortices from control, Magoh, Rbm8a, and Eif4a3 haploinsufficient embryos (generated with Emx1-Cre)
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