scholarly journals APCFZR1 prevents nondisjunction in mouse oocytes by controlling meiotic spindle assembly timing

2012 ◽  
Vol 23 (20) ◽  
pp. 3970-3981 ◽  
Author(s):  
Janet E. Holt ◽  
Simon I. R. Lane ◽  
Phoebe Jennings ◽  
Irene García-Higuera ◽  
Sergio Moreno ◽  
...  
Keyword(s):  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Mitotic Cell ◽  
Meiotic Spindle ◽  
Genome Integrity ◽  
Mitotic Cell Cycle ◽  
Anaphase Promoting Complex ◽  
Mouse Oocytes ◽  
M Phase ◽  
Chromosome Nondisjunction

FZR1 is an anaphase-promoting complex (APC) activator best known for its role in the mitotic cell cycle at M-phase exit, in G1, and in maintaining genome integrity. Previous studies also established that it prevents meiotic resumption, equivalent to the G2/M transition. Here we report that mouse oocytes lacking FZR1 undergo passage through meiosis I that is accelerated by ∼1 h, and this is due to an earlier onset of spindle assembly checkpoint (SAC) satisfaction and APCCDC20 activity. However, loss of FZR1 did not compromise SAC functionality; instead, earlier SAC satisfaction was achieved because the bipolar meiotic spindle was assembled more quickly in the absence of FZR1. This novel regulation of spindle assembly by FZR1 led to premature bivalent attachment to microtubules and loss of kinetochore-bound MAD2. Bivalents, however, were observed to congress poorly, leading to nondisjunction rates of 25%. We conclude that in mouse oocytes FZR1 controls the timing of assembly of the bipolar spindle and in so doing the timing of SAC satisfaction and APCCDC20 activity. This study implicates FZR1 as a major regulator of prometaphase whose activity helps to prevent chromosome nondisjunction.

scholarly journals EMB-30: An APC4 Homologue Required for Metaphase-to-Anaphase Transitions during Meiosis and Mitosis in Caenorhabditis elegans

2000 ◽  
Vol 11 (4) ◽  
pp. 1401-1419 ◽  
Author(s):  
Tokiko Furuta ◽  
Simon Tuck ◽  
Jay Kirchner ◽  
Bryan Koch ◽  
Roy Auty ◽  
...  
Keyword(s):  
Positional Cloning ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Class I ◽  
Meiotic Spindle ◽  
Anaphase Promoting Complex ◽  
Anaphase Onset ◽  
Polar Bodies ◽  
M Phase ◽  
Set Up

Here we show that emb-30 is required for metaphase-to-anaphase transitions during meiosis and mitosis inCaenorhabditis elegans. Germline-specificemb-30 mutant alleles block the meiotic divisions. Mutant oocytes, fertilized by wild-type sperm, set up a meiotic spindle but do not progress to anaphase I. As a result, polar bodies are not produced, pronuclei fail to form, and cytokinesis does not occur. Severe-reduction-of-function emb-30 alleles (class I alleles) result in zygotic sterility and lead to germline and somatic defects that are consistent with an essential role in promoting the metaphase-to-anaphase transition during mitosis. Analysis of the vulval cell lineages in these emb-30(class I) mutant animals suggests that mitosis is lengthened and eventually arrested when maternally contributed emb-30 becomes limiting. By further reducing maternal emb-30 function contributed to class I mutant animals, we show that emb-30 is required for the metaphase-to-anaphase transition in many, if not all, cells. Metaphase arrest in emb-30 mutants is not due to activation of the spindle assembly checkpoint but rather reflects an essential emb-30 requirement for M-phase progression. A reduction in emb-30 activity can suppress the lethality and sterility caused by a null mutation in mdf-1, a component of the spindle assembly checkpoint machinery. This result suggests that delaying anaphase onset can bypass the spindle checkpoint requirement for normal development. Positional cloning established thatemb-30 encodes the likely C. elegansorthologue of APC4/Lid1, a component of the anaphase-promoting complex/cyclosome, required for the metaphase-to-anaphase transition. Thus, the anaphase-promoting complex/cyclosome is likely to be required for all metaphase-to-anaphase transitions in a multicellular organism.

scholarly journals The spindle assembly checkpoint is not essential for CSF arrest of mouse oocytes

2004 ◽  
Vol 167 (6) ◽  
pp. 1037-1050 ◽  
Author(s):  
Chizuko Tsurumi ◽  
Steffen Hoffmann ◽  
Stephan Geley ◽  
Ralph Graeser ◽  
Zbigniew Polanski
Keyword(s):  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Dominant Negative ◽  
Meiotic Spindle ◽  
Anaphase Promoting Complex ◽  
Mouse Oocytes ◽  
Cytostatic Factor ◽  
C Complex ◽  
Meiosis I

In Xenopus oocytes, the spindle assembly checkpoint (SAC) kinase Bub1 is required for cytostatic factor (CSF)-induced metaphase arrest in meiosis II. To investigate whether matured mouse oocytes are kept in metaphase by a SAC-mediated inhibition of the anaphase-promoting complex/cyclosome (APC/C) complex, we injected a dominant-negative Bub1 mutant (Bub1dn) into mouse oocytes undergoing meiosis in vitro. Passage through meiosis I was accelerated, but even though the SAC was disrupted, injected oocytes still arrested at metaphase II. Bub1dn-injected oocytes released from CSF and treated with nocodazole to disrupt the second meiotic spindle proceeded into interphase, whereas noninjected control oocytes remained arrested at metaphase. Similar results were obtained using dominant-negative forms of Mad2 and BubR1, as well as checkpoint resistant dominant APC/C activating forms of Cdc20. Thus, SAC proteins are required for checkpoint functions in meiosis I and II, but, in contrast to frog eggs, the SAC is not required for establishing or maintaining the CSF arrest in mouse oocytes.

scholarly journals The Aurora kinase inhibitor ZM447439 accelerates first meiosis in mouse oocytes by overriding the spindle assembly checkpoint

Reproduction ◽  
2010 ◽  
Vol 140 (4) ◽  
pp. 521-530 ◽  
Author(s):  
Simon I R Lane ◽  
Heng-Yu Chang ◽  
Phoebe C Jennings ◽  
Keith T Jones
Keyword(s):  
Spindle Assembly Checkpoint ◽  
Kinase Inhibitor ◽  
Polar Body ◽  
Spindle Assembly ◽  
Aurora Kinase ◽  
Mitotic Cell ◽  
Cyclin B1 ◽  
Anaphase Promoting Complex ◽  
Mouse Oocytes ◽  
Polar Body Extrusion

Previous studies have established that when maturing mouse oocytes are continuously incubated with the Aurora inhibitor ZM447439, meiotic maturation is blocked. In this study, we observe that by altering the time of addition of the inhibitor, oocyte maturation can actually be accelerated by 1 h as measured by the timing of polar body extrusion. ZM447439 also had the ability to overcome a spindle assembly checkpoint (SAC) arrest caused by nocodazole and so rescue polar body extrusion. Consistent with the ability of the SAC to inhibit cyclin B1 degradation by blocking activation of the anaphase-promoting complex, we could also observe a rescue in cyclin B1 degradation when ZM447439 was added to nocodazole-treated oocytes. The acceleration of the first meiotic division by ZM447439, which has not been achieved previously, and its effects on the SAC are all consistent with the proposed mitotic role of Aurora B in activating the SAC. We hypothesize that Aurora kinase activity controls the SAC in meiosis I, despite differences to the mitotic cell cycle division in spindle architecture brought about by the meiotic mono-orientation of sister kinetochores.

scholarly journals CDC6 regulates both G2/M transition and metaphase-to-anaphase transition during the first meiosis of mouse oocytes

2019 ◽  
Author(s):  
Zi-Yun Yi ◽  
Tie-Gang Meng ◽  
Xue-Shan Ma ◽  
Jian Li ◽  
Chun-Hui Zhang ◽  
...  
Keyword(s):  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Time Lapse ◽  
Cyclin B1 ◽  
Meiotic Spindle ◽  
G2 Arrest ◽  
Mouse Oocytes ◽  
Summary Statement ◽  
Initiation Of Dna Replication ◽  
Oocyte Meiotic Maturation

AbstractCell division cycle protein CDC6 is essential for the initiation of DNA replication. CDC6 was recently shown to inhibit the microtubule-organizing activity of the centrosome. Here, we show that CDC6 is localized to the spindle from Pro-MI to MII stages of oocytes, and it plays important roles at two critical steps of oocyte meiotic maturation. CDC6 depletion facilitated the G2/M transition (GV breakdown, GVBD) through regulation of Cdh1 and cyclin B1 expression and CDK1 phosphorylation in a GVBD-inhibiting culture system containing milrinone. Furthermore, GVBD was significantly decreased after knockdown of cyclin B1 in CDC6-depleted oocytes, indicating that the effect of CDC6 loss on GVBD stimulation was mediated, at least in part, by raising cyclin B1. Knockdown of CDC6 also caused abnormal localization of γ-tubulin, resulting in defective spindles, misaligned chromosomes, cyclin B1 accumulation and spindle assembly checkpoint (SAC) activation, leading to significant Pro-MI/MI arrest and PB1 extrusion failure. These phenotypes were also confirmed by time-lapse live cell imaging analysis. The results indicate that CDC6 is indispensable for maintaining G2 arrest of meiosis and functions in G2/M checkpoint regulation in mouse oocytes. Moreover, CDC6 is also a key player regulating meiotic spindle assembly and metaphase-to-anaphase transition in meiotic oocytes.Summary statementWe show that CDC6 is indispensable for maintaining G2 arrest of mouse oocytes. Moreover, CDC6 is also a key player regulating meiotic spindle assembly and metaphase-to-anaphase transition in meiotic oocytes.

scholarly journals Kinetochore Fibers Are Not Involved in the Formation of the First Meiotic Spindle in Mouse Oocytes, but Control the Exit from the First Meiotic M Phase

1999 ◽  
Vol 146 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Stéphane Brunet ◽  
Angélica Santa Maria ◽  
Philippe Guillaud ◽  
Denis Dujardin ◽  
Jacek Z. Kubiak ◽  
...  
Keyword(s):  
Polar Body ◽  
Meiotic Spindle ◽  
Homologous Chromosomes ◽  
Mouse Oocytes ◽  
Sister Chromatids ◽  
M Phase ◽  
Continuous Presence ◽  
Set Up ◽  
Polar Body Extrusion ◽  
Reductional Division

During meiosis, two successive divisions occur without any intermediate S phase to produce haploid gametes. The first meiotic division is unique in that homologous chromosomes are segregated while the cohesion between sister chromatids is maintained, resulting in a reductional division. Moreover, the duration of the first meiotic M phase is usually prolonged when compared with mitotic M phases lasting 8 h in mouse oocytes. We investigated the spindle assembly pathway and its role in the progression of the first meiotic M phase in mouse oocytes. During the first 4 h, a bipolar spindle forms and the chromosomes congress near the equatorial plane of the spindle without stable kinetochore– microtubule end interactions. This late prometaphase spindle is then maintained for 4 h with chromosomes oscillating in the central region of the spindle. The kinetochore–microtubule end interactions are set up at the end of the first meiotic M phase (8 h after entry into M phase). This event allows the final alignment of the chromosomes and exit from metaphase. The continuous presence of the prometaphase spindle is not required for progression of the first meiotic M phase. Finally, the ability of kinetochores to interact with microtubules is acquired at the end of the first meiotic M phase and determines the timing of polar body extrusion.

scholarly journals DNA damage induces a meiotic arrest in mouse oocytes mediated by the spindle assembly checkpoint

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Josie K. Collins ◽  
Simon I. R. Lane ◽  
Julie A. Merriman ◽  
Keith T. Jones
Keyword(s):  
Dna Damage ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Meiotic Arrest ◽  
Mouse Oocytes
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