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The Journal of Neuroscience, October 24, 2007, 27(43):11769-11775; doi:10.1523/JNEUROSCI.1938-07.2007

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Brief Communications
LKB1 Regulates Neuronal Migration and Neuronal Differentiation in the Developing Neocortex through Centrosomal Positioning

Naoyuki Asada,^1 * Kamon Sanada,^2,3 * and Yoshitaka Fukada¹

¹Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Bunkyo-Ku, Tokyo 113-0033, Japan, ²Department of Developmental Neuroscience, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan, and ³Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan

Correspondence should be addressed to either of the following: Dr. Kamon Sanada, Department of Developmental Neuroscience, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan, Email: kamon_sanada{at}mac.com; or Dr. Yoshitaka Fukada, Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Hongo 7-3-1, Bunkyo-Ku, Tokyo 113-0033, Japan, Email: sfukada{at}mail.ecc.u-tokyo.ac.jp

The cerebral cortex is formed through the coordination of highly organized cellular processes such as neuronal migration and neuronal maturation. Polarity establishment of neurons and polarized regulation of the neuronal cytoskeleton are essential for these events. Here we find that LKB1, the closest homolog of the Caenorhabditis elegans polarity protein Par4, is expressed in the developing neocortex. Knock-down of LKB1 in migrating immature neurons impairs neuronal migration, with alteration of the centrosomal positioning and with uncoupling between the centrosome and nucleus. Furthermore, impairment of LKB1 in differentiating neurons within the cortical plate induces malpositioning of the centrosome at the basal side of the nucleus, instead of the normal apical positioning. This is accompanied with the disruption of axonal and dendritic polarity, resulting in reversed orientation of differentiating neurons. Moreover, LKB1 specifies axon and dendrites identity in vitro. Together, these observations indicate that LKB1 plays a critical role in neuronal migration and neuronal differentiation. Furthermore, we propose that proper neuronal migration and differentiation are intimately coupled to the precise control of the centrosomal positioning/movement directed by LKB1.

Key words: polarity; neuronal migration; LKB1; neuronal differentiation; axon specification; centrosome

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Received April 29, 2007; revised Sept. 14, 2007; accepted Sept. 14, 2007.

Correspondence should be addressed to either of the following: Dr. Kamon Sanada, Department of Developmental Neuroscience, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan, Email: kamon_sanada{at}mac.com; or Dr. Yoshitaka Fukada, Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Hongo 7-3-1, Bunkyo-Ku, Tokyo 113-0033, Japan, Email: sfukada{at}mail.ecc.u-tokyo.ac.jp

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