Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany; Center for Systems Biology Dresden, Dresden, Germany; Max Planck Institute for the Physics of Complex Systems, Dresden, Germany
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany; Center for Systems Biology Dresden, Dresden, Germany; Max Planck Institute for the Physics of Complex Systems, Dresden, Germany
Benjamin Dalton
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany; Center for Systems Biology Dresden, Dresden, Germany; Max Planck Institute for the Physics of Complex Systems, Dresden, Germany
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany; Center for Systems Biology Dresden, Dresden, Germany; Max Planck Institute for the Physics of Complex Systems, Dresden, Germany
Regulation of size and growth is a fundamental problem in biology. A prominent example is the formation of the mitotic spindle, where protein concentration gradients around chromosomes are thought to regulate spindle growth by controlling microtubule nucleation. Previous evidence suggests that microtubules nucleate throughout the spindle structure. However, the mechanisms underlying microtubule nucleation and its spatial regulation are still unclear. Here, we developed an assay based on laser ablation to directly probe microtubule nucleation events in Xenopus laevis egg extracts. Combining this method with theory and quantitative microscopy, we show that the size of a spindle is controlled by autocatalytic growth of microtubules, driven by microtubule-stimulated microtubule nucleation. The autocatalytic activity of this nucleation system is spatially regulated by the limiting amounts of active microtubule nucleators, which decrease with distance from the chromosomes. This mechanism provides an upper limit to spindle size even when resources are not limiting.
