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Jacques Pecreaux — Doing the spindle rock. Mitotic spindle motion in C elegans one-cell embryo.

Speaker :

Jacques Pecreaux, Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany

When :

Monday 15 February at 11h

Where :

C023 (RDC LR6 côté Centre Blaise Pascal)

Title :

Doing the spindle rock. Mitotic spindle motion in C elegans one-cell embryo.

Abstract :

During asymmetric division of the C. elegans zygote, the mitotic spindle is first centered and, only in late metaphase, displaced towards the posterior of the cell in response to polarity cues. 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. Combining a semi-microscopic model and an accurate tracking of the centrosomes, we could account for the posterior displacement of the spindle and its anaphase oscillations. We validated the model observing that a threshold number of force generators is required to create spindle oscillations. Having characterized these oscillations, we used them as a tool to investigate spindle mechanics ; we showed that the precise temporal coordination of the build-up and die-down of the oscillations, together with posterior displacement, can be accounted for by a gradual increase of cortical force generators persistence (processivity). Combining modeling of oscillations and molecular biology approach, we showed that the actin-myosin cortex plays a novel role as a stiff platform to anchor the microtubule machinery required for mitosis. We also characterized the membrane tubes dependent on force generators, which are pulled from the plasma membrane into the cell when weakening actin-myosin cortex. These tubes offers a “tube assay” that reveals the positions and numbers of the force generating complexes ; using this assay, we suggested that spindle centering is achieved independently of pulling forces responsible of posterior displacement of the spindle. These results are not consistent with the commonly held belief that centering is due to pulling. Furthermore, the positioning of the spindle is remarkably precise within a cell and remarkably similar from cell to cell. Indeed, measurement revealed typically a 0.5 % accuracy in positioning the spindle. We therefore propose that there must be feedback between spindle position and microtubule dynamics that increases the fidelity of positioning. A Fourier analysis of the positional fluctuation showed a mechanism equivalent to a spring and a dashpot, suggesting that centering may be due to pushing of microtubules against the cell cortex. These studies show the relevance of biophysics modeling combined to advanced image processing to investigate spindle positioning and pave the way to a broader modeling of cell division aiming to decipher the molecular mechanism at work.

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