Microtubule organizing centers regulate spindle positioning in mouse oocytes

Dev Cell. 2022 Jan 24;57(2):197-211.e3. doi: 10.1016/j.devcel.2021.12.011. Epub 2022 Jan 13.

Abstract

During female meiosis I (MI), spindle positioning must be tightly regulated to ensure the fidelity of the first asymmetric division and faithful chromosome segregation. Although the role of F-actin in regulating these critical processes has been studied extensively, little is known about whether microtubules (MTs) participate in regulating these processes. Using mouse oocytes as a model system, we characterize a subset of MT organizing centers that do not contribute directly to spindle assembly, termed mcMTOCs. Using laser ablation, STED super-resolution microscopy, and chemical manipulation, we show that mcMTOCs are required to regulate spindle positioning and faithful chromosome segregation during MI. We discuss how forces exerted by F-actin on the spindle are balanced by mcMTOC-nucleated MTs to anchor the spindle centrally and to regulate its timely migration. Our findings provide a model for asymmetric cell division, complementing the current F-actin-based models, and implicate mcMTOCs as a major player in regulating spindle positioning.

Keywords: MTOC; cytoplasmic MTOC; meiosis; microtubule; oocyte; spindle migration; spindle positioning.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / physiology
  • Actins / physiology
  • Animals
  • Asymmetric Cell Division / physiology
  • Chromosome Segregation / physiology
  • Female
  • Meiosis / physiology
  • Mice
  • Mice, Inbred C57BL
  • Microtubule-Organizing Center / metabolism
  • Microtubule-Organizing Center / physiology*
  • Microtubules / metabolism
  • Microtubules / physiology
  • Oocytes / metabolism*
  • Oocytes / physiology
  • Spindle Apparatus / metabolism
  • Spindle Apparatus / physiology*

Substances

  • Actins