Abstract
ABSTRACTSpindle length varies dramatically across species and during early development to segregate chromosomes optimally. Both intrinsic factors, such as regulatory molecules, and extrinsic factors, such as cytoplasmic volume, determine spindle length scaling. However, the properties that govern spindle shape and whether these features can be modulated remain unknown. Here, we analyzed quantitatively how the molecular players which regulate microtubule dynamics control the kinetics of spindle formation and shape. We find that, in absence of Clasp1 and Clasp2, spindle assembly is biphasic due to unopposed inward pulling forces from the kinetochore-fibers and that kinetochore-fibers also alter spindle geometry. We demonstrate that spindle shape scaling is independent of the nature of the molecules that regulate dynamic microtubule properties, but is dependent on the steady-state metaphase spindle length. The shape of the spindle scales anisotropically with increasing length. Our results suggest that intrinsic mechanisms control the shape of the spindle to ensure the efficient capture and alignment of chromosomes independently of spindle length.
Highlights
The self-organization and maintenance of a bipolar spindle is critical to ensure chromosome alignment and the equal distribution of genetic material to the daughter cells during mitosis
We find that the regulators of microtubule dynamics Clasp1, Clasp2, the chromokinesin Kid, and the kinesin-8 Kif18a contribute to the kinetics of bipolar spindle formation and spindle geometry
To probe how spindle length and shape is set during spindle elongation, we analyzed the dynamics of spindle geometry formation
Summary
The self-organization and maintenance of a bipolar spindle is critical to ensure chromosome alignment and the equal distribution of genetic material to the daughter cells during mitosis. Upon depletion of Clasp1, Clasp2, or Clasp1/Clasp2 codepletion, the steady-state spindle length was shorter following STLC washout than in control cells (Fig. 1B,C; supplementary material Fig. S1C). This elongation phase was followed by a contraction phase to a steady-state length that was significantly shorter than control cells (8.7 6 1.1 mm, 9.3 6 1.2 mm, and 6.7 6 0.9 mm for Clasp1, Clasp2, and Clasp1/ Clasp2 depletion, respectively, supplementary material Table S1).
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