Abstract
Asymmetric division of the C. elegans zygote is due to the posterior-directed movement of the mitotic spindle during metaphase and anaphase. During this movement along the anterior-posterior axis, the spindle oscillates transversely. These motions are thought to be driven by a force-generating complex-possibly containing the motor protein cytoplasmic dynein-that is located at the cell cortex and pulls on microtubules growing out from the spindle poles. A theoretical analysis indicates that the oscillations might arise from mechanical coordination of the force-generating motors, and this coordination is mediated by the load dependence of the motors' detachment from the microtubules. The model predicts that the motor activity must exceed a threshold for oscillations to occur. We have tested the existence of a threshold by using RNA interference to gradually reduce the levels of dynein light intermediate chain as well as GPR-1 and GPR-2 that are involved in the G protein-mediated regulation of the force generators. We found an abrupt cessation of oscillations as expected if the motor activity dropped below a threshold. Furthermore, we can account for the complex choreography of the mitotic spindle-the precise temporal coordination of the buildup and die-down of the transverse oscillations with the posterior displacement-by a gradual increase in the processivity of a single type of motor machinery during metaphase and anaphase. The agreement between our results and modeling suggests that the force generators themselves have the intrinsic capability of generating oscillations when opposing forces exceed a threshold.
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