TY - JOUR T1 - The c-Jun N-Terminal Kinase Activator Dual Leucine Zipper Kinase Regulates Axon Growth and Neuronal Migration in the Developing Cerebral Cortex JF - The Journal of Neuroscience JO - J. Neurosci. SP - 11992 LP - 12002 DO - 10.1523/JNEUROSCI.2272-06.2006 VL - 26 IS - 46 AU - Syu-ichi Hirai AU - De Feng Cui AU - Takaki Miyata AU - Masaharu Ogawa AU - Hiroshi Kiyonari AU - Yoko Suda AU - Shinichi Aizawa AU - Yumi Banba AU - Shigeo Ohno Y1 - 2006/11/15 UR - http://www.jneurosci.org/content/26/46/11992.abstract N2 - Mammalian corticogenesis substantially depends on migration and axon projection of newborn neurons that are coordinated by a yet unidentified molecular mechanism. Dual leucine zipper kinase (DLK) induces activation of c-Jun N-terminal kinase (JNK), a molecule that regulates morphogenesis in various organisms. We show here, using gene targeting in mice, that DLK is indispensable for establishing axon tracts, especially those originating from neocortical pyramidal neurons of the cerebrum. Direct and quantitative analysis of radial migration of pyramidal neurons using slice culture and a time-lapse imaging system revealed that acceleration around the subplate was affected by DLK gene disruption and by administration of a JNK inhibitor. Phosphorylation of JNK substrates, including c-Jun and doublecortin, and of JNK itself at the activation loop were partially affected in brains of DLK-deficient mouse embryos. These data suggest that DLK plays a significant role in the coordinated regulation of radial migration and axon projection by modulating JNK activity. ER -