Journal
JOURNAL OF CELL BIOLOGY
Volume 167, Issue 2, Pages 245-256Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200406008
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Funding
- NIBIB NIH HHS [P41 EB002025] Funding Source: Medline
- NIGMS NIH HHS [R01 GM068966, R01 GM068966-02, R01 GM68966] Funding Source: Medline
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Regulation of the mitotic spindle's position is important for cells to divide asymmetrically. Here, we use Caenorhabditis elegans embryos to provide the first analysis of the temporal regulation of forces that asymmetrically position a mitotic spindle. We find that asymmetric pulling forces, regulated by cortical PAR proteins, begin to act as early as prophase and prometaphase, even before the spindle forms and shifts to a posterior position. The spindle does not shift asymmetrically during these early phases due to a tethering force, mediated by astral microtubules that reach the anterior cell cortex. We show that this tether is normally released after spindle assembly and independently of anaphase entry. Monitoring microtrubule dynamics by photobleaching segments of microtubules during anaphase revealed that spindle microtubules do not undergo significant poleward flux in C. elegans. Together with the known absence of anaphase A, these data suggest that the major forces contributing to chromosome separation during anaphase originate outside the spindle. We propose that the forces positioning the mitotic spindle asymmetrically are tethered until after the time of spindle assembly and that these same forces are used later to drive chromosome segregation at anaphase.
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