Activation of Aurora-A is essential for neuronal migration via modulation of microtubule organization

Takako Takitoh, Kanako Kumamoto, Chen Chi Wang, Makoto Sato, Shiori Toba, Anthony Wynshaw-Boris, Shinji Hirotsune

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Neuronal migration is a critical feature to ensure proper location and wiring of neurons during cortical development. Postmitotic neurons migrate from the ventricular zone into the cortical plate to establish neuronal lamina in an "inside-out" gradient of maturation. Here, we report that the mitotic kinase Aurora-A is critical for the regulation of microtubule organization during neuronal migration via an Aurora-A-NDEL1 pathway in the mouse. Suppression of Aurora-A activity by inhibitors or siRNA resulted in severe impairment of neuronal migration of granular neurons. In addition, in utero injection of the Aurora-A kinase-dead mutant provoked defective migration of cortical neurons. Furthermore, we demonstrated that suppression of Aurora-A impaired microtubule modulation in migrating neurons. Interestingly, suppression of CDK5 by an inhibitor or siRNA reduced Aurora-A activity and NDEL1 phosphorylation by Aurora-A, which led to defective neuronal migration. We found that CDK5RAP2 is a key molecule that mediates functional interaction and is essential for centrosomal targeting of Aurora-A. Our observations demonstrated novel and surprising cross talk between Aurora-A and CDK5 during neuronal migration.

Original languageEnglish
Pages (from-to)11050-11066
Number of pages17
JournalJournal of Neuroscience
Volume32
Issue number32
DOIs
Publication statusPublished - 08-08-2012

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All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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