Embryonic Mitosis Research Articles

Cyclin B3 is a dominant fast-acting cyclin that drives rapid early embryonic mitoses.

Mitosis in early embryos often proceeds at a rapid pace, but how this pace is achieved is not understood. Here, we show that cyclin B3 is the dominant driver of rapid embryonic mitoses in the C. elegans embryo. Cyclins B1 and B2 support slow mitosis (NEBD to anaphase ∼600 s), but the presence of cyclin B3 dominantly drives the approximately threefold faster mitosis observed in wildtype. Multiple mitotic events are slowed down in cyclin B1 and B2-driven mitosis, and cyclin B3-associated Cdk1 H1 kinase activity is ∼25-fold more active than cyclin B1-associated Cdk1. Addition of cyclin B1 to fast cyclin B3-only mitosis introduces an ∼60-s delay between completion of chromosome alignment and anaphase onset; this delay, which is important for segregation fidelity, is dependent on inhibitory phosphorylation of the anaphase activator Cdc20. Thus, cyclin B3 dominance, coupled to a cyclin B1-dependent delay that acts via Cdc20 phosphorylation, sets the rapid pace and ensures mitotic fidelity in the early C. elegans embryo.

Spindle morphology changes between meiosis and mitosis driven by CK2 regulation of the Ran pathway.

The transition from meiotic divisions in the oocyte to embryonic mitoses is a critical step in animal development. Despite negligible changes to cell size and shape, following fertilization the small, barrel-shaped meiotic spindle is replaced by a large zygotic spindle that nucleates abundant astral microtubules at spindle poles. To probe underlying mechanisms, we applied a drug screening approach using Ciona eggs and found that inhibition of Casein Kinase 2 (CK2) caused a shift from meiotic to mitotic-like spindle morphology with nucleation of robust astral microtubules, an effect reproduced in cytoplasmic extracts prepared from Xenopus eggs. In both species, CK2 activity decreased at fertilization. Phosphoproteomic differences between Xenopus meiotic and mitotic extracts that also accompanied CK2 inhibition pointed to RanGTP-regulated factors as potential targets. Interfering with RanGTP-driven microtubule formation suppressed astral microtubule growth caused by CK2 inhibition. These data support a model in which CK2 activity attenuation at fertilization leads to activation of RanGTP-regulated microtubule effectors that induce mitotic spindle morphology.

The translational oscillation in oocyte and early embryo development.

Translation is critical for development as transcription in the oocyte and early embryo is silenced. To illustrate the translational changes during meiosis and consecutive two mitoses of the oocyte and early embryo, we performed a genome-wide translatome analysis. Acquired data showed significant and uniform activation of key translational initiation and elongation axes specific to M-phases. Although global protein synthesis decreases in M-phases, translation initiation and elongation activity increases in a uniformly fluctuating manner, leading to qualitative changes in translation regulation via the mTOR1/4F/eEF2 axis. Overall, we have uncovered a highly dynamic and oscillatory pattern of translational reprogramming that contributes to the translational regulation of specific mRNAs with different modes of polysomal occupancy/translation that are important for oocyte and embryo developmental competence. Our results provide new insights into the regulation of gene expression during oocyte meiosis as well as the first two embryonic mitoses and show how temporal translation can be optimized. This study is the first step towards a comprehensive analysis of the molecular mechanisms that not only control translation during early development, but also regulate translation-related networks employed in the oocyte-to-embryo transition and embryonic genome activation.

BUB-1-bound PLK-1 directs CDC-20 kinetochore recruitment to ensure timely embryonic mitoses

During mitosis, chromosomes assemble kinetochores to dynamically couple with spindle microtubules.1,2 Kinetochores also function as signaling hubs directing mitotic progression by recruiting and controlling the fate of the anaphase promoting complex/cyclosome (APC/C) activator CDC-20.3,4,5 Kinetochores either incorporate CDC-20 into checkpoint complexes that inhibit the APC/C or dephosphorylate CDC-20, which allows it to interact with and activate the APC/C.4,6 The importance of these two CDC-20 fates likely depends on the biological context. In human somatic cells, the major mechanism controlling mitotic progression is the spindle checkpoint. By contrast, progression through mitosis during the cell cycles of early embryos is largely checkpoint independent.7,8,9,10 Here, we first show that CDC-20 phosphoregulation controls mitotic duration in the C.elegans embryo and defines a checkpoint-independent temporal mitotic optimum for robust embryogenesis. CDC-20 phosphoregulation occurs at kinetochores and in the cytosol. At kinetochores, the flux of CDC-20 for local dephosphorylation requires an ABBA motif on BUB-1 that directly interfaces with the structured WD40 domain of CDC-20.6,11,12,13 We next show that a conserved "STP" motif in BUB-1 that docks the mitotic kinase PLK-114 is necessary for CDC-20 kinetochore recruitment and timely mitotic progression. The kinase activity of PLK-1 is required for CDC-20 to localize to kinetochores and phosphorylates the CDC-20-binding ABBA motif of BUB-1 to promote BUB-1-CDC-20 interaction and mitotic progression. Thus, the BUB-1-bound pool of PLK-1 ensures timely mitosis during embryonic cell cycles by promoting CDC-20 recruitment to the vicinity of kinetochore-localized phosphatase activity.

Expert consensus on the morphological evaluation of human cleavage-stage embryos and blastocysts.

Expert consensus on the morphological evaluation of human cleavage-stage embryos and blastocysts.

O-040 Investigating why early embryonic mitoses are highly error prone by real time imaging

Abstract Maintenance of genomic integrity during early embryogenesis is essential for faithful embryonic development. However, mitotic errors during preimplantation development are surprisingly common and despite the fundamental importance of the cell divisions at the beginning of life, the mechanisms that control the correct progression through mitosis during pre-implantation development are not well characterized. The sensitivity of mammalian embryos to light and its demanding in vitro culture requirements have limited real-time imaging during the first embryonic divisions in the past. Today, advances in light-sheet microscopy allow in toto imaging of preimplantation mouse development from zygote to blastocyst at single chromosome resolution and enable us to study spindle assembly, chromosome restructuring and segregation. This presentation will discuss the insights we have gained by real-time imaging of the first cell divisions in mammalian life, and the role of the key molecular mechanisms that regulate mitosis during the critical first stages of embryo development.

Fertilization signatures as biomarkers of embryo quality.

Fertilization underpins the vital transition from gametic meiosis to embryonic mitosis. For decades, in human IVF, microscopic observation at a single time point has limited our appreciation of the morphokinetic complexity of this process. More recently, the introduction of time lapse technology-also enhanced by combination with artificial intelligence-has revealed the finest morphokinetic details of the beginning of human development. Overall, a picture has finally emerged in which the precise timing, morphology and geometry of several fertilization events offer clues to predict the fate of the embryo-a key aspect of assisted reproduction. In this scenario, correct unfolding of intra- and interpronuclear rearrangements emerge as a crucial factor to create a platform able to preserve genetic and cellular integrity at the first mitotic cleavage.

Haplotype-aware inference of human chromosome abnormalities

Extra or missing chromosomes-a phenomenon termed aneuploidy-frequently arise during human meiosis and embryonic mitosis and are the leading cause of pregnancy loss, including in the context of in vitro fertilization (IVF). While meiotic aneuploidies affect all cells and are deleterious, mitotic errors generate mosaicism, which may be compatible with healthy live birth. Large-scale abnormalities such as triploidy and haploidy also contribute to adverse pregnancy outcomes, but remain hidden from standard sequencing-based approaches to preimplantation genetic testing for aneuploidy (PGT-A). The ability to reliably distinguish meiotic and mitotic aneuploidies, as well as abnormalities in genome-wide ploidy, may thus prove valuable for enhancing IVF outcomes. Here, we describe a statistical method for distinguishing these forms of aneuploidy based on analysis of low-coverage whole-genome sequencing data, which is the current standard in the field. Our approach overcomes the sparse nature of the data by leveraging allele frequencies and linkage disequilibrium (LD) measured in a population reference panel. The method, which we term LD-informed PGT-A (LD-PGTA), retains high accuracy down to coverage as low as 0.05 × and at higher coverage can also distinguish between meiosis I and meiosis II errors based on signatures spanning the centromeres. LD-PGTA provides fundamental insight into the origins of human chromosome abnormalities, as well as a practical tool with the potential to improve genetic testing during IVF.

Centriole-less pericentriolar material serves as a microtubule organizing center at the base of C. elegans sensory cilia

During mitosis in animal cells, the centrosome acts as a microtubule organizing center (MTOC) to assemble the mitotic spindle. MTOC function at the centrosome is driven by proteins within the pericentriolar material (PCM), however the molecular complexity of the PCM makes it difficult to differentiate the proteins required for MTOC activity from other centrosomal functions. We used the natural spatial separation of PCM proteins during mitotic exit to identify a minimal module of proteins required for centrosomal MTOC function in C.elegans. Using tissue-specific degradation, we show that SPD-5, the functional homolog of CDK5RAP2, is essential for embryonic mitosis, while SPD-2/CEP192 and PCMD-1, which are essential in the one-cell embryo, are dispensable. Surprisingly, although the centriole is known to be degraded in the ciliated sensory neurons in C.elegans,1-3 we find evidence for "centriole-less PCM" at the base of cilia and use this structure as a minimal testbed to dissect centrosomal MTOC function. Super-resolution imaging revealed that this PCM inserts inside the lumen of the ciliary axoneme and directly nucleates the assembly of dendritic microtubules toward the cell body. Tissue-specific degradation in ciliated sensory neurons revealed a role for SPD-5 and the conserved microtubule nucleator γ-TuRC, but not SPD-2 or PCMD-1, in MTOC function at centriole-less PCM. This MTOC function was in the absence of regulation by mitotic kinases, highlighting the intrinsic ability of these proteins to drive microtubule growth and organization and further supporting a model that SPD-5 is the primary driver of MTOC function at the PCM.

Centriole-Less Pericentriolar Material Serves as a Microtubule Organizing Center at the Base of C. elegans Sensory Cilia

During mitosis in animal cells, the centrosome acts as a microtubule organizing center (MTOC) to assemble the mitotic spindle. MTOC function at the centrosome is driven by proteins within the pericentriolar material (PCM), however the molecular complexity of the PCM makes it difficult to differentiate the proteins required for MTOC activity from other centrosomal functions. We used the natural spatial separation of PCM proteins during mitotic exit to identify a minimal module of proteins required for centrosomal MTOC function in C. elegans. Using tissue specific degradation, we show that SPD-5, the functional homolog of CDK5RAP2, is essential for embryonic mitosis while SPD-2/CEP192 and PCMD-1, which are essential in the zygote, are dispensable. Surprisingly, although the centriole is known to be degraded in the ciliated sensory neurons in C. elegans , we find evidence for “centriole-less PCM” at the base of cilia and use this structure as a minimal testbed to dissect centrosomal MTOC function. Super-resolution imaging revealed that this PCM inserts inside the lumen of the ciliary axoneme and directly nucleates the assembly of dendritic microtubules towards the cell body. Tissue-specific degradation in ciliated sensory neurons revealed a role for SPD-5 and the conserved microtubule nucleator [[EQUATION]] -TuRC, but not SPD-2 or PCMD-1, in MTOC function at centriole-less PCM. This MTOC function was in the absence of regulation by mitotic kinases, highlighting the intrinsic ability of these proteins to drive microtubule growth and organization and further supporting a model that SPD-5 is the primary driver of MTOC function at the PCM.

Site-directed mutagenesis in bread and durum wheat via pollination by cas9/guide RNA-transgenic maize used as haploidy inducer.

Site-directed mutagenesis in bread and durum wheat via pollination by cas9/guide RNA-transgenic maize used as haploidy inducer.

The Lid/KDM5 histone demethylase complex activates a critical effector of the oocyte-to-zygote transition.

Following fertilization of a mature oocyte, the formation of a diploid zygote involves a series of coordinated cellular events that ends with the first embryonic mitosis. In animals, this complex developmental transition is almost entirely controlled by maternal gene products. How such a crucial transcriptional program is established during oogenesis remains poorly understood. Here, we have performed an shRNA-based genetic screen in Drosophila to identify genes required to form a diploid zygote. We found that the Lid/KDM5 histone demethylase and its partner, the Sin3A-HDAC1 deacetylase complex, are necessary for sperm nuclear decompaction and karyogamy. Surprisingly, transcriptomic analyses revealed that these histone modifiers are required for the massive transcriptional activation of deadhead (dhd), which encodes a maternal thioredoxin involved in sperm chromatin remodeling. Unexpectedly, while lid knock-down tends to slightly favor the accumulation of its target, H3K4me3, on the genome, this mark was lost at the dhd locus. We propose that Lid/KDM5 and Sin3A cooperate to establish a local chromatin environment facilitating the unusually high expression of dhd, a key effector of the oocyte-to-zygote transition.

Molecular aspects of aneuploidy in preimplantation human embryos: A mini-review

Objective Focus and analyze on the two aneuploidy types (meiotic and mitotic) in preimplantation human embryos, their causes and possible molecular mechanisms involved. Design Mini-review. Materials and Methods Search performed in MEDLINE database under the keywords; aneuploidy, molecular mechanisms, preimplantation embryos. Results Aneuploidy is the major obstacle in order to achieve successful pregnancies in IVF world. Specifically, more than 50% of preimplantation embryos are aneuploid and unable to achieve pregnancies and live births. In reproductive aged women, aneuploidy rate in oocytes, caused by an error-prone meiotic chromosome segregation mechanism, is reaching 20-30%, in contrast to human sperm, that only 1-8% have an abnormal chromosomal content. Meiotic aneuploidy can occur from MI non-disjunction, MII non-disjunction and MI or MII pre-division. Maternal age is the major critical factor related to aneuploidy; 50% of the oocytes from advanced age women (≥ 40 years old) are aneuploid due to meiotic errors. Cohesive chromosome connections are weakened with increasing maternal age mainly due to very small amounts of a major cohesin component, the Rec8. Additionally, recombination failure, which varies between chromosomes, can also lead to meiotic aneuploidy. Genomic errors can also arise during post-fertilization mitotic divisions, resulting in embryonic mosaicism. The mechanisms leading to embryonic mosaicism during embryonic mitosis are; non-disjunction, anaphase lagging and endoreplication. Mitotic aneuploidies rise from 63% at the cleavage stage to 95% in blastocyst stage human embryos. Defects in mitotic spindle assembly checkpoint (SAC) can result to high chromosome missegregation levels both in vitro and in vivo. Furthermore, malfunction of cohesins, possibly due to inactivation of STAG2 and/or overexpression of seperase, leads in premature chromosome separation, while delay in their removal may result in non-disjunction. Finally, embryonic mitotic aneuploidy can be caused by extra-nuclear DNA formation (micronucleation) from lagging chromosomes with severe DNA damage and by severe paternal sperm defects. Conclusions The high rate of chromosomal aneuploidies may arise mostly during the first or second meiotic divisions, especially in advanced maternal age women, but also can arise in the postzygotic stage during the mitotic divisions of cleavage stage and blastocyst embryos, resulting in mosaicism. Further work and analysis on the molecular mechanisms that lead to meiotic and mitotic aneuploidy in preimplantation embryos, can reveal improved clinical strategies to reduce the occurrence of aneuploidy and consequently improve the success rates of IVF. Disclosures None. Funding None. Focus and analyze on the two aneuploidy types (meiotic and mitotic) in preimplantation human embryos, their causes and possible molecular mechanisms involved. Mini-review. Search performed in MEDLINE database under the keywords; aneuploidy, molecular mechanisms, preimplantation embryos. Aneuploidy is the major obstacle in order to achieve successful pregnancies in IVF world. Specifically, more than 50% of preimplantation embryos are aneuploid and unable to achieve pregnancies and live births. In reproductive aged women, aneuploidy rate in oocytes, caused by an error-prone meiotic chromosome segregation mechanism, is reaching 20-30%, in contrast to human sperm, that only 1-8% have an abnormal chromosomal content. Meiotic aneuploidy can occur from MI non-disjunction, MII non-disjunction and MI or MII pre-division. Maternal age is the major critical factor related to aneuploidy; 50% of the oocytes from advanced age women (≥ 40 years old) are aneuploid due to meiotic errors. Cohesive chromosome connections are weakened with increasing maternal age mainly due to very small amounts of a major cohesin component, the Rec8. Additionally, recombination failure, which varies between chromosomes, can also lead to meiotic aneuploidy. Genomic errors can also arise during post-fertilization mitotic divisions, resulting in embryonic mosaicism. The mechanisms leading to embryonic mosaicism during embryonic mitosis are; non-disjunction, anaphase lagging and endoreplication. Mitotic aneuploidies rise from 63% at the cleavage stage to 95% in blastocyst stage human embryos. Defects in mitotic spindle assembly checkpoint (SAC) can result to high chromosome missegregation levels both in vitro and in vivo. Furthermore, malfunction of cohesins, possibly due to inactivation of STAG2 and/or overexpression of seperase, leads in premature chromosome separation, while delay in their removal may result in non-disjunction. Finally, embryonic mitotic aneuploidy can be caused by extra-nuclear DNA formation (micronucleation) from lagging chromosomes with severe DNA damage and by severe paternal sperm defects. The high rate of chromosomal aneuploidies may arise mostly during the first or second meiotic divisions, especially in advanced maternal age women, but also can arise in the postzygotic stage during the mitotic divisions of cleavage stage and blastocyst embryos, resulting in mosaicism. Further work and analysis on the molecular mechanisms that lead to meiotic and mitotic aneuploidy in preimplantation embryos, can reveal improved clinical strategies to reduce the occurrence of aneuploidy and consequently improve the success rates of IVF.

Molecular aspects of aneuploidy in preimplantation human embryos: a mini-review

Aneuploidy is a major obstacle in achieving successful pregnancies in in vitro fertilization (IVF) procedures. In practice, more than 50% of preimplantation embryos are aneuploid and unable to achieve viable pregnancy. Analysis of human sperm and oocytes has showed that aneuploidy in preimplantation embryos is predominantly caused by an error-prone meiotic chromosome segregation mechanism in oocytes. In reproductive aged women, aneuploidy rate in human oocytes is reaching 20–30%, in contrast to human sperm, that only 1–8% have an abnormal chromosomal content. Meiotic aneuploidy can occur from meiosis I (MI) non-disjunction, meiosis II (MII) non-disjunction and MI or MII pre-division. Multiple factors have been suggested to contribute to meiotic aneuploidy including maternal age and impaired cohesin complex formation. Maternal age is the major critical factor related to aneuploidy; 50% of the oocytes from advanced age women (≥40 years old) are aneuploid due to meiotic errors. The relationship between maternal age and altered recombination, which is entirely dependent on the context of chromosomes, can also contribute to development of aneuploidy. Genomic errors can also arise during post-fertilization mitotic divisions, resulting in embryonic mosaicism. The mechanisms leading to embryonic mosaicism during embryonic mitosis are; non-disjunction, anaphase lagging and endoreplication. Mosaicism exists in ~15–90% of all cleavage stage human embryos and in general, mitotic aneuploidies rise from 63% at the cleavage stage to 95% in blastocyst stage. Relaxation or absence of cell cycle checkpoints are possible mechanisms that have been hypothesized to account for mitotic aneuploidy in early human preimplantation embryos. Specifically, defects in spindle assembly checkpoint (SAC) and malfunction of cohesion complexes, can lead to premature chromosome separation, while delay in their removal may result in non-disjunction. Furthermore, extra-nuclear DNA formation generated from lagging chromosomes with severe DNA damage (i.e., micronucleation), may be a major mechanism of mitotic aneuploidy. Once source of aneuploidy involves paternal factor is related to mitotic aneuploidy, as severe sperm defects and advanced paternal age can increase the percentage of mitotic abnormalities in embryos. Further work and analysis into the molecular mechanisms that lead to meiotic and mitotic aneuploidy in preimplantation embryos, could inspire clinical strategies to reduce the occurrence of aneuploidy and consequently improve the success rates of IVF.

Identification of a variant-specific phosphorylation of TH2A during spermiogenesis

Tissue-specific histone variant incorporation into chromatin plays dynamic and important roles in tissue development. Testis is one such tissue, and a number of testis-specific histone variants are expressed that have unique roles. While it is expected that such variants acquire post-transcriptional modifications to be functional, identification of variant-specific histone modifications is challenging because of the high similarity of amino acid sequences between canonical and variant versions. Here we identified a novel phosphorylation on TH2A, a germ cell-specific histone H2A variant. TH2A-Thr127 is unique to the variant and phosphorylated concomitant with chromatin condensation including spermiogenesis and early embryonic mitosis. In sperm chromatin, phosphorylated TH2A-Thr127 (=pTH2A) is co-localized with H3.3 at transcriptional starting sites of the genome, and subsequently becomes absent from the paternal genome upon fertilization. Notably, pTH2A is recurrent and accumulated in the pericentromeric heterochromatin of both paternal and maternal chromosomes in the first mitosis of embryos, suggesting its unique regulation during spermiogenesis and early embryogenesis.

A \u2018selfish\u2019 B chromosome induces genome elimination by disrupting the histone code in the jewel wasp Nasonia vitripennis

Intragenomic conflict describes a phenomenon in which genetic elements act ‘selfishly’ to gain a transmission advantage at the expense of the whole genome. A non-essential, selfish B chromosome known as Paternal Sex Ratio (PSR) induces complete elimination of the sperm-derived hereditary material in the jewel wasp Nasonia vitripennis. PSR prevents the paternal chromatin from forming chromosomes during the first embryonic mitosis, leading to its loss. Although paternally transmitted, PSR evades self-elimination in order to be inherited. We examined important post-translational modifications to the DNA packaging histones on the normal genome and the PSR chromosome in the fertilized embryo. Three histone marks – H3K9me2,3, H3K27me1, and H4K20me1 – became abnormally enriched and spread to ectopic positions on the sperm’s chromatin before entry into mitosis. In contrast, other histone marks and DNA methylation were not affected by PSR, suggesting that its effect on the paternal genome is specific to a subset of histone marks. Contrary to the paternally derived genome, the PSR chromosome was visibly devoid of the H3K27me1 and H4K20me1 marks. These findings strongly suggest that PSR causes paternal genome elimination by disrupting at least three histone marks following fertilization, while PSR avoids self-elimination by evading two of these marks.

Expression of the novel maternal centrosome assembly factor Wdr8 is required for vertebrate embryonic mitoses

The assembly of the first centrosome occurs upon fertilisation when male centrioles recruit pericentriolar material (PCM) from the egg cytoplasm. The mechanisms underlying the proper assembly of centrosomes during early embryogenesis remain obscure. We identify Wdr8 as a novel maternally essential protein that is required for centrosome assembly during embryonic mitoses of medaka (Oryzias latipes). By CRISPR–Cas9-mediated knockout, maternal/zygotic Wdr8-null (m/zWdr8−/−) blastomeres exhibit severe defects in centrosome structure that lead to asymmetric division, multipolar mitotic spindles and chromosome alignment errors. Via its WD40 domains, Wdr8 interacts with the centriolar satellite protein SSX2IP. Combining targeted gene knockout and in vivo reconstitution of the maternally essential Wdr8–SSX2IP complex reveals an essential link between maternal centrosome proteins and the stability of the zygotic genome for accurate vertebrate embryogenesis. Our approach provides a way of distinguishing maternal from paternal effects in early embryos and should contribute to understanding molecular defects in human infertility.

Maternal MEMI Promotes Female Meiosis II in Response to Fertilization in Caenorhabditis elegans

In most animals, female meiosis completes only after fertilization. Sperm entry has been implicated in providing a signal for the initiation of the final meiotic processes; however, a maternal component required for this process has not been previously identified. We report the characterization of a novel family of three highly similar paralogs (memi-1, memi-2, memi-3) that encode oocyte-specific proteins. A hyper-morphic mutation memi-1(sb41) results in failure to exit female meiosis II properly; however, loss of all three paralogs results in a "skipped meiosis II" phenotype. Mutations that prevent fertilization, such as fer-1(hc1), also cause a skipped meiosis II phenotype, suggesting that the MEMI proteins represent a maternal component of a postfertilization signal that specifies the meiosis II program. MEMI proteins are degraded before mitosis and sensitive to ZYG-11, a substrate-specific adapter for cullin-based ubiquitin ligase activity, and the memi-1(sb41) mutation results in inappropriate persistence of the MEMI-1 protein into mitosis. Using an RNAi screen for suppressors of memi-1(sb41), we identified a sperm-specific PP1 phosphatase, GSP-3/4, as a putative sperm component of the MEMI pathway. We also found that MEMI and GSP-3/4 proteins can physically interact via co-immunoprecipitation. These results suggest that sperm-specific PP1 and maternal MEMI proteins act in the same pathway after fertilization to facilitate proper meiosis II and the transition into embryonic mitosis.

From meiosis to mitosis – the sperm centrosome defines the kinetics of spindle assembly after fertilization in Xenopus

Bipolar spindle assembly in the vertebrate oocyte relies on a self-organization chromosome-dependent pathway. Upon fertilization, the male gamete provides a centrosome, and the first and subsequent embryonic divisions occur in the presence of duplicated centrosomes that act as dominant microtubule organizing centres (MTOCs). The transition from meiosis to embryonic mitosis involves a necessary adaptation to integrate the dominant chromosome-dependent pathway with the centrosomes to form the bipolar spindle. Here, we took advantage of the Xenopus laevis egg extract system to mimic in vitro the assembly of the first embryonic spindle and investigate the respective contributions of the centrosome and the chromosome-dependent pathway to the kinetics of the spindle bipolarization. We found that centrosomes control the transition from the meiotic to the mitotic spindle assembly mechanism. By defining the kinetics of spindle bipolarization, the centrosomes ensure their own positioning to each spindle pole and thereby their essential correct inheritance to the two first daughter cells of the embryo for the development of a healthy organism.

From meiosis to mitosis - the sperm centrosome defines the kinetics of spindle assembly after fertilization in Xenopus.

Bipolar spindle assembly in the vertebrate oocyte relies on a self-organization chromosome-dependent pathway. Upon fertilization, the male gamete provides a centrosome, and the first and subsequent embryonic divisions occur in the presence of duplicated centrosomes that act as dominant microtubule organizing centres (MTOCs). The transition from meiosis to embryonic mitosis involves a necessary adaptation to integrate the dominant chromosome-dependent pathway with the centrosomes to form the bipolar spindle. Here, we took advantage of the Xenopus laevis egg extract system to mimic in vitro the assembly of the first embryonic spindle and investigate the respective contributions of the centrosome and the chromosome-dependent pathway to the kinetics of the spindle bipolarization. We found that centrosomes control the transition from the meiotic to the mitotic spindle assembly mechanism. By defining the kinetics of spindle bipolarization, the centrosomes ensure their own positioning to each spindle pole and thereby their essential correct inheritance to the two first daughter cells of the embryo for the development of a healthy organism.