NuMA assemblies organize microtubule asters to establish spindle bipolarity in acentrosomal human cells

In most animal cells, mitotic spindle formation is mediated by coordination of centrosomal and acentrosomal pathways. At the onset of mitosis, centrosomes promote spindle bipolarization. However, the mechanism through which the acentrosomal pathways facilitate the establishment of spindle bipolarity in early mitosis is not completely understood. In this study, we show the critical roles of nuclear mitotic apparatus protein (NuMA) in the generation of spindle bipolarity in acentrosomal human cells. In acentrosomal human cells, we found that small microtubule asters containing NuMA formed at the time of nuclear envelope breakdown. In addition, these asters were assembled by dynein and the clustering activity of NuMA. Subsequently, NuMA organized the radial array of microtubules, which incorporates Eg5, and thus facilitated spindle bipolarization. Importantly, in cells with centrosomes, we also found that NuMA promoted the initial step of spindle bipolarization in early mitosis. Overall, these data suggest that canonical centrosomal and NuMA‐mediated acentrosomal pathways redundantly promote spindle bipolarity in human cells. Synopsis Mitotic spindle formation in animal cells involves both centrosomal and acentrosomal pathways. Studies on acentrosomal human cells suggest that canonical centrosomal and NuMA/dynein‐mediated mechanisms may redundantly promote spindle biploarity early in mitosis. NuMA promotes spindle bipolarity in the absence of centrosomes. Dynein and the clustering activity of NuMA facilitate acentrosomal spindle pole organization. NuMA organizes the radial array of microtubules, which incorporates kinesin Eg5 to facilitate spindle bipolarization. NuMA also promotes the initial step of spindle bipolarization in cells with centrosomes. Graphical Abstract Studies on acentrosomal human cells suggest that canonical centrosomal and NuMA/dynein‐mediated mechanisms may redundantly promote establishment of bipolar mitotic spindles after nuclear envelope breakdown.