Mammalian oocytes are notoriously prone to chromosome segregation errors leading to aneuploidy. The spindle provides the machinery for accurate chromosome segregation during cell division. Mammalian oocytes lack centrioles and, therefore, the meiotic spindle relies on the organization of numerous acentriolar microtubule organizing centers into two poles (polar MTOCs, pMTOCs). The traditional view is that, in mammalian oocytes, microtubules are the sole cytoskeletal component responsible for regulating pMTOC organization and spindle assembly. We identified a novel F-actin pool that surrounds pMTOCs, forming F-actin cage-like structure. We demonstrated that F-actin localization on the spindle depends on unconventional myosins X and VIIb. Selective disruption of spindle-localized F-actin, using myosin X/VIIb knockdown oocytes or photoswitchable Optojasp-1, perturbed pMTOC organization, leading to unfocused spindle poles and chromosome missegregation. Here, we unveil an important function of F-actin in regulating pMTOC organization, a critical process for ensuring the fidelity of meiotic spindle formation and proper chromosome segregation.

Animal Sciences Research Center University of Missouri Columbia MO 65211 USA

Department of Chemistry University of Pennsylvania Philadelphia PA 19104 6323 USA

Department of Gynaecology Obstetrics and Neonatology 1st Faculty of Medicine Charles University and General University Hospital Prague Apolinarska 18 128 08 Prague Czech Republic

Department of Zoology Faculty of Science Charles University Vinicna 7 128 44 Prague Czech Republic

Division of Biology and Biological Engineering California Institute of Technology Pasadena CA USA

Friedrich Schiller Universität Institut für Organische Chemie und Makromolekulare Chemie Humboldtstr 10 07743 Jena Germany

Laboratory of Reproductive Biology Institute of Biotechnology of the Czech Academy of Sciences BIOCEV Prumyslova 595 252 50 Vestec Czech Republic

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Nat Commun. 2025 Sep 19;16(1):8323. doi: 10.1038/s41467-025-63586-w. PubMed

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