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Evaluation of the Spindle Assembly Checkpoint Integrity in Mouse Oocytes
Published on: September 13, 2022
Spindle assembly checkpoint regulates mitotic cell cycle progression during preimplantation embryo development
Yanchang Wei1, Saima Multi, Cai-Rong Yang
1State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Plos One
|July 2, 2011
Summary
The spindle assembly checkpoint (SAC) is crucial for accurate chromosome segregation in early mouse embryos. Its depletion leads to aneuploidy, developmental delays, and implantation failure.
Area of Science:
- Developmental Biology
- Cell Biology
- Genetics
Background:
- Aneuploidy, resulting from chromosome segregation errors, leads to severe reproductive and developmental issues.
- The role of the spindle assembly checkpoint (SAC) in ensuring mitotic fidelity during early embryonic development remains largely unknown.
Purpose of the Study:
- To investigate the function of key spindle assembly checkpoint (SAC) components (Bub3, BubR1, Mad2) in mouse preimplantation embryos.
- To determine if SAC is essential for regulating mitotic cell cycle progression and preventing aneuploidy during early development.
Main Methods:
- Utilized overexpression and RNA interference (RNAi) to manipulate SAC component levels in mouse embryos.
- Assessed effects on cell cycle progression, chromosome segregation, aneuploidy, implantation, and development.
Main Results:
- Overexpression of SAC components halted metaphase-anaphase transition, inhibiting sister chromatid segregation.
- RNAi-mediated depletion of SAC components accelerated cell cycle progression, leading to chromosome misalignment, aneuploidy, and micronuclei formation.
- SAC-depleted embryos failed to arrest at metaphase when treated with nocodazole, indicating a loss of checkpoint function.
Conclusions:
- The spindle assembly checkpoint (SAC) is essential for regulating mitotic cell cycle progression in cleavage-stage mouse embryos.
- SAC plays a critical role in maintaining genomic stability and ensuring successful preimplantation development.
Related Concept Videos
02:19The Spindle Assembly Checkpoint
The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
02:19The Spindle Assembly Checkpoint
The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
02:50Spindle Assembly
Spindle assembly occurs through three, often coexisting, pathways – the centrosome-mediated pathway, the chromatin-mediated pathway, and the microtubule-mediated pathway – collectively contributing to form a robust spindle apparatus.
In most cells, centrosomes are the primary microtubule nucleation centers. In the centrosome-mediated pathway, the G2-prophase transition triggers centrosome maturation and increased microtubule nucleation. Progressive nucleation results in a microtubule array...
In most cells, centrosomes are the primary microtubule nucleation centers. In the centrosome-mediated pathway, the G2-prophase transition triggers centrosome maturation and increased microtubule nucleation. Progressive nucleation results in a microtubule array...
02:17Separation of Sister Chromatids
At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
At the onset of anaphase, separase, a proteolytic enzyme, is...
At the onset of anaphase, separase, a proteolytic enzyme, is...
02:15M-Cdk Drives Transition Into Mitosis
Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
02:15M-Cdk Drives Transition Into Mitosis
Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...