The spindle assembly checkpoint and the spatial activation of Polo kinase determine the duration of cell division and prevent tumor formation

Author summaryStem cells divide asymmetrically and exist in limited numbers in tissues to ensure their development and repair. To do so, stem cells ensure a rigorous progression of mitotic events to avoid chromosome segregation errors during cell division, and formation of aneuploid daughter cells with impaired proliferative capacities. Moreover, during mitosis, these stem cells are characterized by their polarization along an apical-basal axis. The orientation of the mitotic spindle along this axis allows the asymmetric distribution of cell fate determinants after cell division. This differential segregation is required to contain stem cell amplification and tumor formation. How mitotic progression is coupled to cell polarization at the molecular level during stem cell asymmetric division is therefore a critical question. We show here that the levels of active Polo kinase regulate the duration of cell division. Polo activation is regulated via a direct activating phosphorylation by Aurora A and Aurora B kinases. Moreover, activation of Polo kinase by Aurora A is essential to maintain polarization of mitotic stem cells and consequently to prevent tumor formation. Altogether, our results strongly suggest that an Aurora-dependent phosphorylation cascade leading to the activation of Polo kinase regulates the coupling between mitotic progression and tissue homeostasis. The maintenance of a restricted pool of asymmetrically dividing stem cells is essential for tissue homeostasis. This process requires the control of mitotic progression that ensures the accurate chromosome segregation. In addition, this event is coupled to the asymmetric distribution of cell fate determinants in order to prevent stem cell amplification. How this coupling is regulated remains poorly described. Here, using asymmetrically dividing Drosophila neural stem cells (NSCs), we show that Polo kinase activity levels determine timely Cyclin B degradation and mitotic progression independent of the spindle assembly checkpoint (SAC). This event is mediated by the direct phosphorylation of Polo kinase by Aurora A at spindle poles and Aurora B kinases at centromeres. Furthermore, we show that Aurora A-dependent activation of Polo is the major event that promotes NSC polarization and together with the SAC prevents brain tumor growth. Altogether, our results show that an Aurora/Polo kinase module couples NSC mitotic progression and polarization for tissue homeostasis.