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Spindle-localized F-actin regulates polar MTOC organization and the fidelity of meiotic spindle formation

Edgar J Soto-Moreno1, Nourhan N Ali1, Florian Küllmer2

  • 1Division of Animal Sciences, University of Missouri, Columbia, MO, USA.

Nature Communications
|September 19, 2025
PubMed

Insights

Mammalian oocytes have a newly discovered F-actin structure crucial for organizing the meiotic spindle. This F-actin network ensures proper chromosome segregation, preventing aneuploidy during cell division.

Area of Science:

  • Cell Biology
  • Reproductive Biology
  • Cytoskeleton Dynamics

Background:

  • Mammalian oocytes frequently experience chromosome segregation errors, resulting in aneuploidy.
  • The meiotic spindle, essential for accurate chromosome segregation, lacks centrioles in mammalian oocytes.
  • Spindle assembly in these oocytes relies on acentriolar microtubule organizing centers (MTOCs) forming two poles (pMTOCs).

Purpose of the Study:

  • To investigate the role of cytoskeletal components beyond microtubules in mammalian oocyte spindle organization.
  • To identify novel structures regulating polar microtubule organizing centers (pMTOCs) and meiotic spindle formation.

Main Methods:

  • Identification and localization of F-actin structures associated with pMTOCs in mouse oocytes.
  • Functional disruption of spindle-localized F-actin using myosin X/VIIb knockdown and Optojasp-1.
  • Analysis of pMTOC organization, spindle pole focusing, and chromosome segregation fidelity.

Main Results:

  • A previously unrecognized F-actin pool forms cage-like structures surrounding pMTOCs.
  • Spindle-localized F-actin is dependent on unconventional myosins X and VIIb.
  • Disruption of F-actin cages leads to perturbed pMTOC organization, unfocused spindle poles, and chromosome missegregation.

Conclusions:

  • Spindle-localized F-actin plays a critical role in regulating pMTOC organization during meiosis in mammalian oocytes.
  • This F-actin network is essential for ensuring the fidelity of meiotic spindle formation and proper chromosome segregation.
  • Unconventional myosins X and VIIb are key regulators of this F-actin function.

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