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

Soto-Moreno, Edgar J.; Ali, Nourhan N.; Küllmer, Florian; Nasufovic, Veselin; Frolikova, Michaela; Tepla, Olga; Masata, Jaromir; Trauner, Dirk; Patterson, Amanda A.; Arndt, Hans-Dieter; Komrskova, Katerina; Zernicka-Goetz, Magdalena; Glover, David M.; Balboula, Ahmed Z.

doi:10.1038/s41467-025-63586-w

Published September 19, 2025 | Version Published

Journal Article Open

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

1. University of Missouri
2. Friedrich Schiller University Jena
3. Institute of Biotechnology
4. General University Hospital in Prague
5. University of Pennsylvania
6. Charles University
7. California Institute of Technology

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, mouse meiotic spindle relies on the organization of numerous acentriolar microtubule organizing centers into two poles (polar microtubule organizing centers, pMTOCs). The traditional view is that, in mammalian oocytes, microtubules are the sole cytoskeletal component responsible for regulating pMTOC organization and spindle assembly. We identify a previously unrecognized F-actin pool that surrounds pMTOCs, forming F-actin cage-like structure. We demonstrate 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, perturbs pMTOC organization, leading to unfocused spindle poles and chromosome missegregation. Here, we unveil an important function of spindle-localized F-actin in regulating pMTOC organization, a critical process for ensuring the fidelity of meiotic spindle formation and proper chromosome segregation.

Copyright and License

© 2025, The Author(s). Open Access. This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

Acknowledgement

The authors would like to thank all members of the Glover lab and the Balboula lab for their valuable help and discussions. The authors would like to thank Melina Schuh for providing the MAP4-UtrCH-GFP and Cep192-mCherry constructs. We thank Samantha Bosland, University of Missouri, for creating the schematic illustrations. We thank Alexander Jurkevich (the Molecular Cytology Core, University of Missouri) and Ivan Novotny (Light Microscopy Core Facility, Institute of Molecular Genetics of the Czech Academy of Sciences) for their support with the STED super-resolution imaging. This research was funded by the NIH (R35 GM142537) to A.Z.B. This research was further supported by Marie Sklodowska-Curie Fellowship 706170 (Horizon 2020, European Commission) to D.M.G. and A.Z.B., Czech Grant Agency (GA22-30494S and GA25-173155) to K.K., Czech Health Research Council (NW24-08-00048), BIOCEV (CZ.1.05/1.1.00/02.0109) to K.K. and J.M., and Institute of Biotechnology of the Czech Academy of Sciences (RVO 86652036) to K.K. and J.M., and Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany´s Excellence Strategy – EXC 2051 – Project-ID 390713860 to HAD, and the Light Microscopy Core Facility, IMG, Prague, Czech Republic, supported by MEYS – LM2023050 and RVO – 68378050-KAV-NPUI.

Data Availability

No sequence or proteomic data has been generated in this study. All the data can be found in either the main text or the supplementary materials. All raw image data are available from the corresponding author upon request. Source data are provided in this paper.

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