4.7 Article

A computational model predicts Xenopus meiotic spindle organization

Journal

JOURNAL OF CELL BIOLOGY
Volume 191, Issue 7, Pages 1239-1249

Publisher

ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201006076

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Funding

  1. National Institutes of Health [DP1 OD000818]
  2. Miller Institute for Basic Research in Science
  3. National Science Foundation
  4. Cancer Research Coordinating Committee
  5. BioMS (Center for Modeling and Simulation in the Biosciences)
  6. Volkswagenstiftung [HFSP RGY084]
  7. E.U.

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The metaphase spindle is a dynamic bipolar structure crucial for proper chromosome segregation, but how microtubules (MTs) are organized within the bipolar architecture remains controversial. To explore MT organization along the pole-to-pole axis, we simulated meiotic spindle assembly in two dimensions using dynamic MTs, a MT cross-linking force, and a kinesin-5-like motor. The bipolar structures that form consist of antiparallel fluxing MTs, but spindle pole formation requires the addition of a NuMA-like minus-end cross-linker and directed transport of MT depolymerization activity toward minus ends. Dynamic instability and minus-end depolymerization generate realistic MT lifetimes and a truncated exponential MT length distribution. Keeping the number of MTs in the simulation constant, we explored the influence of two different MT nucleation pathways on spindle organization. When nucleation occurs throughout the spindle, the simulation quantitatively reproduces features of meiotic spindles assembled in Xenopus egg extracts.

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