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The Journal of Neuroscience, November 21, 2007, 27(47):12829-12838; doi:10.1523/JNEUROSCI.1014-07.2007

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Development/Plasticity/Repair
Cyclin-Dependent Kinase 5 Is Required for Control of Neuroblast Migration in the Postnatal Subventricular Zone

Yuki Hirota,^1,2,3 Toshio Ohshima,^4,5 Naoko Kaneko,^1,2,3 Makiko Ikeda,¹ Takuji Iwasato,⁶ Ashok B. Kulkarni,⁷ Katsuhiko Mikoshiba,⁵ Hideyuki Okano,^3,8 and Kazunobu Sawamoto^1,2,3

¹Department of Developmental and Regenerative Biology, Institute of Molecular Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan, ²Bridgestone Laboratory of Developmental and Regenerative Neurobiology and ³Department of Physiology, Keio University School of Medicine, Tokyo 160-8582, Japan, ⁴Department of Life Science and Medical Bio-Science, Waseda University, Tokyo 169-8555, Japan, ⁵Laboratory for Developmental Neurobiology and ⁶Laboratory for Behavioral Genetics, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan, ⁷Functional Genomics Section, Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, and ⁸Solution Oriented Research for Science and Technology, Japan Science and Technology Corporation, Saitaima 332-0012, Japan

Correspondence should be addressed to Kazunobu Sawamoto, Department of Developmental and Regenerative Biology, Institute of Molecular Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan. Email: sawamoto{at}med.nagoya-cu.ac.jp

At the lateral wall of the lateral ventricles in the adult rodent brain, neuroblasts form an extensive network of elongated cell aggregates called chains in the subventricular zone and migrate toward the olfactory bulb. The molecular mechanisms regulating this migration of neuroblasts are essentially unknown. Here, we report a novel role for cyclin-dependent kinase 5 (Cdk5), a neuronal protein kinase, in this process. Using in vitro and in vivo conditional knock-out experiments, we found that Cdk5 deletion impaired the chain formation, speed, directionality, and leading process extension of the neuroblasts in a cell-autonomous manner. These findings suggest that Cdk5 plays an important role in neuroblast migration in the postnatal subventricular zone.

Key words: Cdk5; neuroblast; migration; subventricular zone; rostral migratory stream; postnatal neurogenesis

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Received March 6, 2007; revised Oct. 1, 2007; accepted Oct. 3, 2007.

Correspondence should be addressed to Kazunobu Sawamoto, Department of Developmental and Regenerative Biology, Institute of Molecular Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan. Email: sawamoto{at}med.nagoya-cu.ac.jp

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