Self-organization of MTOCs Replaces Centrosome Function During Acentrosomal Spindle Assembly in Live Mouse Oocytes

Cell. 2007 Aug 10;130(3):484-98. doi: 10.1016/j.cell.2007.06.025.

Abstract

Chromosome segregation in mammalian oocytes is driven by a microtubule spindle lacking centrosomes. Here, we analyze centrosome-independent spindle assembly by quantitative high-resolution confocal imaging in live maturing mouse oocytes. We show that spindle assembly proceeds by the self-organization of over 80 microtubule organizing centers (MTOCs) that form de novo from a cytoplasmic microtubule network in prophase and that functionally replace centrosomes. Initially distributed throughout the ooplasm, MTOCs congress at the center of the oocyte, where they contribute to a massive, Ran-dependent increase of the number of microtubules after nuclear envelope breakdown and to the individualization of clustered chromosomes. Through progressive MTOC clustering and activation of kinesin-5, the multipolar MTOC aggregate self-organizes into a bipolar intermediate, which then elongates and thereby establishes chromosome biorientation. Finally, a stable barrel-shaped acentrosomal metaphase spindle with oscillating chromosomes and astral-like microtubules forms that surprisingly exhibits key properties of a centrosomal spindle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Polarity / physiology
  • Cells, Cultured
  • Centrosome / metabolism*
  • Centrosome / physiology
  • Female
  • Interphase / physiology
  • Mice
  • Mice, Inbred C57BL
  • Microtubule-Organizing Center / metabolism*
  • Microtubule-Organizing Center / physiology
  • Microtubules / physiology
  • Oocytes / metabolism*
  • Spindle Apparatus / metabolism*