Synergy between Multiple Microtubule-Generating Pathways Confers Robustness to Centrosome-Driven Mitotic Spindle Formation

• Published in: Developmental cell 2014-01, Vol.28 (1), p.81-93
• Main Authors: Hayward, Daniel, Metz, Jeremy, Pellacani, Claudia, Wakefield, James G.
• Format: Article
• Language: English
• Subjects: Animals; Centromere - metabolism; Drosophila; Drosophila - genetics; Drosophila - metabolism; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Microtubules - metabolism; Spindle Apparatus - metabolism
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2013.12.001

The mitotic spindle is defined by its organized, bipolar mass of microtubules, which drive chromosome alignment and segregation. Although different cells have been shown to use different molecular pathways to generate the microtubules required for spindle formation, how these pathways are coordinated within a single cell is poorly understood. We have tested the limits within which the Drosophila embryonic spindle forms, disrupting the inherent temporal control that overlays mitotic microtubule generation, interfering with the molecular mechanism that generates new microtubules from preexisting ones, and disrupting the spatial relationship between microtubule nucleation and the usually dominant centrosome. Our work uncovers the possible routes to spindle formation in embryos and establishes the central role of Augmin in all microtubule-generating pathways. It also demonstrates that the contributions of each pathway to spindle formation are integrated, highlighting the remarkable flexibility with which cells can respond to perturbations that limit their capacity to generate microtubules. [Display omitted] •Chromosome-driven MT generation exists in embryos and is dependent on D-HURP•Centrosome disruption results in cytoplasmic aMTOCs, driving spindle formation•Augmin generates MTs from centrosomal, chromatin, and aMTOC MTs indiscriminately•Reducing one pathway synergistically increases MT growth of the remaining pathways Hayward et al. explore the limits within which Drosophila embryonic mitotic spindles can form. By disrupting temporal control of microtubule generation and interfering with microtubule generation pathways, they uncover complementary routes to spindle formation, demonstrating that removal of one microtubule-generating pathway results in a compensatory increase from the others.