Although force-balance ideas had previously been proposed to explain metaphase chromosome positioning ( 9, 10), Saunders and Hoyt’s work appears to be the first force-balance model of the spindle structure. After the discovery that kinesin-14s appear to contribute counteracting forces that pull spindle poles together ( 8), Saunders and Hoyt ( 8) proposed the “force-balance model,” in which spindle bipolarity arises from the coordination between outward-directed forces from sliding of interpolar MTs that separate spindle poles and inward-directed forces that pull the poles together. Hagan and Yanagida ( 6) noted that kinesin-5s in fission yeast contribute both to spindle pole separation and to antiparallel interdigitation of MTs that are initially predominantly parallel, an essential structural transition for the establishment of a bipolar spindle in organisms with closed mitosis. Kinesin-5 motors, which push spindle poles apart and generate a bipolar spindle, were discovered in yeasts ( 4– 7). Our model can guide the identification of new, multifaceted strategies to induce mitotic catastrophes these would constitute novel strategies for cancer chemotherapy. We also identify characteristic failed states of spindle assembly-the persistent monopole, X spindle, separated asters, and short spindle, which are avoided by the creation and maintenance of antiparallel microtubule overlaps. When kinesin-5 motors are present, their bidirectionality is essential, but spindles can form in the presence of passive cross-linkers alone. By varying the features of our model, we identify a set of functions essential for the generation and stability of spindle bipolarity. Our model results agree quantitatively with our experiments in fission yeast, thereby establishing a minimal system with which to interrogate collective self-assembly. We began with physical properties of fission-yeast spindle pole body size and microtubule number, kinesin-5 motors, kinesin-14 motors, and passive cross-linkers. We describe a physical model that exhibits de novo bipolar spindle formation. Microtubules, motors, and cross-linkers are important for bipolarity, but the mechanisms necessary and sufficient for spindle assembly remain unknown. Bipolar spindles form from a monopolar initial condition this is the most fundamental construction problem that the spindle must solve. Ultimately, expanding this to other core cellular systems and experimentally interrogating such systems in organisms from all major lineages may start outlining the routes to and eventual manifestation of the cellular diversity of eukaryotic life.Mitotic spindles use an elegant bipolar architecture to segregate duplicated chromosomes with high fidelity. We illustrate how the interpretation of divergent SAC systems in eukaryotic species is facilitated by combining detailed molecular knowledge of the SAC and extensive comparative genome analyses. Here, we review the evolutionary dynamics of the spindle assembly checkpoint (SAC), a signaling network that guards fidelity of chromosome segregation. Deep understanding of these modifications will not only explain cellular diversity, but will also uncover different ways to execute similar processes and expose the evolutionary ‘rules’ that shape the molecular networks. The tremendous diversity in eukaryotic life forms can ultimately be traced back to evolutionary modifications at the level of molecular networks.
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