This differential segregation is required to contain stem cell amplification and tumor formation. The orientation of the mitotic spindle along this axis allows the asymmetric distribution of cell fate determinants after cell division. Moreover, during mitosis, these stem cells are characterized by their polarization along an apical-basal axis. To do so, stem cells are subjected to a rigorous progression of mitotic events to avoid chromosome segregation errors during cell division, and formation of aneuploid daughter cells with impaired proliferative capacities. Stem cells divide asymmetrically and exist in limited numbers in tissues to ensure their development and repair.
Altogether, our results show that an Aurora/Polo kinase module couples NSC mitotic progression and polarization for tissue homeostasis.
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. This event is mediated by the direct phosphorylation of Polo kinase by Aurora A at spindle poles and Aurora B kinases at centromeres. 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).
How this coupling is regulated remains poorly described. In addition, this event is coupled to the asymmetric distribution of cell fate determinants in order to prevent stem cell amplification. This process requires the control of mitotic progression that ensures the accurate chromosome segregation. The maintenance of a restricted pool of asymmetrically dividing stem cells is essential for tissue homeostasis.
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