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

Lee, Cheng-Yu and Andersen, Ryan O. and Cabernard, Clemens and Manning, Laurina and Tran, Khoa D. and Lanskey, Marcus J. and Bashirullah, Arash and Doe, Chris Q.. (2006) Drosophila Aurora-A kinase inhibits neuroblast self-renewal by regulating aPKC/Numb cortical polarity and spindle orientation. Genes & development, Vol. 20, H. 24. pp. 3464-3474.

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Official URL: http://edoc.unibas.ch/dok/A5844123

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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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Growth and Development (Cabernard)
UniBasel Contributors:Cabernard, Clemens
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Cold Spring Harbor Laboratory
ISSN:0890-9369
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:08 Jun 2012 06:55
Deposited On:08 Jun 2012 06:45

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