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Spindle assembly checkpoint acquisition at the mid-blastula transition.

Maomao Zhang1, Priyanka Kothari2, Michael A Lampson1

  • 1Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America; Cell and Molecular Biology Graduate Group, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.

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Summary

The spindle assembly checkpoint (SAC) is maternally programmed, not dependent on transcription or cell cycle changes. Zebrafish studies reveal a developmental timer regulates SAC acquisition during early embryogenesis.

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Area of Science:

  • Cell Biology
  • Developmental Biology
  • Genetics

Background:

  • The spindle assembly checkpoint (SAC) ensures accurate chromosome segregation during mitosis.
  • Functional checkpoints, including the SAC, are typically acquired during the mid-blastula transition (MBT) in metazoan embryos.
  • The precise mechanisms governing SAC acquisition at the MBT remain largely unknown.

Purpose of the Study:

  • To investigate the regulatory mechanisms underlying spindle assembly checkpoint (SAC) acquisition during early zebrafish embryogenesis.
  • To test proposed models for SAC acquisition, including dependence on zygotic transcription, Chk1 kinase activity, nuclear to cytoplasmic ratio, or a developmental timer.

Main Methods:

  • Utilized zebrafish embryos as a model system.
  • Investigated SAC acquisition independently of zygotic transcription.
  • Experimentally manipulated cell cycle length and Chk1 kinase activity.
  • Assessed the relationship between SAC acquisition and the nuclear to cytoplasmic (N:C) ratio.

Main Results:

  • SAC acquisition at the MBT was found to be independent of zygotic transcription, suggesting maternal programming.
  • Precocious cell cycle lengthening and Chk1 kinase activation were insufficient to trigger SAC acquisition.
  • SAC acquisition was demonstrated to be uncoupled from the nuclear to cytoplasmic (N:C) ratio thresholds.

Conclusions:

  • The spindle assembly checkpoint (SAC) acquisition during the mid-blastula transition is not dependent on zygotic transcription, Chk1 activity, or N:C ratio.
  • Findings strongly support a model where SAC acquisition is regulated by a maternally programmed developmental timer, independent of other MBT events.