The role of the spindle midzone during chromosome segregation

Abstract

The faithful segregation of chromosomes during mitosis is essential for the health and survival of any eukaryotic organisms. Any failure in this process has detrimental consequences such as developmental abnormalities and cancer. ­­­­­During mitosis microtubules assemble into a bipolar spindle that segregates the sister chromatids in anaphase. Recent publications have high-lighted the importance of the spindle midzone, the region between the chromosomes, for the process of chromosome segregation. A number of publications have led to a model of midzone formation and function that relies on a combination of microtubule organization by bundling, regulation of microtubule growth dynamics and motor driven microtubule sliding (Fig.1A). In contrast, other publications have proposed an opposing model, in which microtubule polymerization in the midzone, independent of motor proteins, generates the force to segregate chromosomes (Fig. 1B). This shows that we still have a limited understanding of the mechanisms of the spindle midzone, in particular the role of microtubule dynamics in this process. Combining a detailed 3D structural analysis by electron tomography with state-of-the art light microscopy we have found that the spindle midzone in C. elegans as well as in mammalian cells is composed of different microtubule subclasses that differ in their dynamics. Thus, suggesting a possible regulation of microtubule growth during anaphase. In addition, we found that while microtubules of the midzone move polewards, the length of the antiparallel Microtubule overlap zone in the spindle midzone is constant throughout anaphase and independent of cortical pulling forces. This observation strongly suggests a role for microtubule polymerization in the midzone. Using a combination of genetic approaches and mathematical modeling we will determine the molecular basis by which midzone MTs are organized and their dynamics are controlled to generate a sliding force that segregates chromosomes.