The mitotic spindle has a crucial role in ensuring the accurate segregation of chromosomes into the two daughter cells during cell division, which is paramount for maintaining genome integrity. 1 It is a self-organized and dynamic macromolecular structure that is constructed from microtubules, microtubule-associated proteins and motor proteins. Thirty years of research have led to the identification of centrosome-, chromatin- and microtubule-mediated microtubule nucleation pathways that each contribute to mitotic spindle assembly. Far from being redundant pathways, data are now emerging regarding how they function together to ensure the timely completion of mitosis. We are also beginning to comprehend the multiple mechanisms by which cells regulate spindle scaling. Together, this research has increased our understanding of how cells coordinate hundreds of proteins to assemble the dynamic, precise and robust structure that is the mitotic spindle.
The assembly of a bipolar spindle is essential for the accurate segregation of chromosomes during both meiosis and mitosis. The mechanisms of meiotic and mitotic spindle assembly differ to some extent; Mitotic spindle assembly is dependent on the tightly regulated nucleation of microtubules, which form the major structural component of the mitotic spindle. Microtubules are assembled from dimers of α- and β-tubulin, a process that is initiated from γ-tubulin ring complexes (γTuRCs). These complexes have a 13-fold symmetry that functions as a template for the assembly of the ring of 13 protofilaments that make up a growing microtubule. The γTuRC also serves as a cap for the microtubule minus end, whereas tubulin dimers are mostly added to the microtubule plus end. Microtubules continuously polymerize and depolymerize, undergoing rapid cycles of growth and shrinkage before ultimately disassembling. This process, termed dynamic instability, is important for the rapid remodelling of the interphase cytoskeleton as cells enter mitosis and for spindle assembly. Mitotic spindle assembly results in an antiparallel, bipolar microtubule array that consists of three broad categories of microtubules (MTs): kinetochore MTs (K-MTs), astral MTs (A-MTs) and non-kinetochore MTs (nK-MTs)5 (FIG. 1).