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Regulation of stem cell self-renewal versus differentiation is critical for embryonic development and adult tissue homeostasis.  Drosophila  larval neuroblasts divide asymmetrically to self-renew, and are a model system for studying stem cell self-renewal. Here we identify three mutations showing increased brain neuroblast numbers that map to the  aurora-A  gene, which encodes a conserved kinase implicated in human cancer. Clonal analysis and time-lapse imaging in  aurora-A  mutants show single neuroblasts generate multiple neuroblasts (ectopic self-renewal). This phenotype is due to two independent neuroblast defects: abnormal atypical protein kinase C (aPKC)/Numb cortical polarity and failure to align the mitotic spindle with the cortical polarity axis.  numb  mutant clones have ectopic neuroblasts, and Numb overexpression partially suppresses  aurora-A  neuroblast overgrowth (but not spindle misalignment). Conversely, mutations that disrupt spindle alignment but not cortical polarity have increased neuroblasts. We conclude that Aurora-A and Numb are novel inhibitors of neuroblast self-renewal and that spindle orientation regulates neuroblast self-renewal.

Drosophila Aurora-A kinase inhibits neuroblast self-renewal by regulating aPKC/Numb cortical polarity and spindle orientation