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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 Küller2

  • 1Animal Sciences Research Center, University of Missouri, Columbia, MO 65211, USA.

Biorxiv : the Preprint Server for Biology
|July 14, 2025
PubMed

Insights

F-actin, not just microtubules, organizes spindle poles in mammalian oocytes. This actin structure is crucial for preventing chromosome segregation errors and aneuploidy during meiosis.

Area of Science:

  • Cell Biology
  • Reproductive Biology
  • Cytoskeleton Dynamics

Background:

  • Mammalian oocytes are prone to aneuploidy due to chromosome segregation errors.
  • The meiotic spindle, essential for chromosome segregation, lacks centrioles in mammalian oocytes.
  • Spindle assembly relies on organizing acentriolar microtubule organizing centers into polar MTOCs.

Purpose of the Study:

  • To investigate the role of F-actin in the organization of polar MTOCs in mammalian oocytes.
  • To identify novel cytoskeletal components involved in meiotic spindle assembly.
  • To understand the mechanisms preventing chromosome missegregation in oocytes.

Main Methods:

  • Identification of F-actin localization around polar MTOCs, forming cage-like structures.
  • Demonstration of F-actin dependence on unconventional myosins X and VIIb for spindle localization.
  • Selective disruption of spindle F-actin using myosin knockdown and Optojasp-1.

Main Results:

  • A novel F-actin pool associated with polar MTOCs was discovered.
  • Myosins X and VIIb mediate F-actin recruitment to the meiotic spindle.
  • Disruption of spindle F-actin led to perturbed polar MTOC organization, unfocused poles, and chromosome missegregation.

Conclusions:

  • F-actin plays a critical, previously unrecognized role in regulating polar MTOC organization.
  • This F-actin function is essential for proper meiotic spindle formation and chromosome segregation fidelity.
  • The findings challenge the traditional view of microtubules as the sole regulators of spindle assembly in oocytes.
Keywords:
AneuploidyF-actinMTOCMeiosisOocyteSpindle

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