title: Drosophila Aurora-A kinase inhibits neuroblast self-renewal by regulating aPKC/Numb cortical polarity and spindle orientation.
abstract: 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.
authors.affiliation: Institutes of Neuroscience and Molecular Biology, Howard Hughes Medical Institute, University of Oregon, Eugene, Oregon 97403, USA.
authors.forename: Cheng-Yu
authors.initials: CY
authors.lastname: Lee
authors.forename: Ryan O
authors.initials: RO
authors.lastname: Andersen
authors.forename: Clemens
authors.initials: C
authors.lastname: Cabernard
authors.forename: Laurina
authors.initials: L
authors.lastname: Manning
authors.forename: Khoa D
authors.initials: KD
authors.lastname: Tran
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Lanskey
authors.forename: Arash
authors.initials: A
authors.lastname: Bashirullah
authors.forename: Chris Q
authors.initials: CQ
authors.lastname: Doe
mesh_terms: D000818:Animals; D064127:Aurora Kinases; D001921:Brain / Q000166:cytology / Q000196:embryology; D018797:Cell Cycle Proteins / Q000502:physiology; D002454:Cell Differentiation; D016764:Cell Polarity / Q000502:physiology; D004330:Drosophila / Q000166:cytology* / Q000254:growth & development; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D007605:Juvenile Hormones / Q000502:physiology*; D007814:Larva / Q000033:anatomy & histology / Q000166:cytology / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D008941:Spindle Apparatus / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology
chemical_list: D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D007605:Juvenile Hormones; C060606:numb protein, Drosophila; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases