JNK activator DLK regulates axon growth and neuronal migration in the developing cerebral cortex　理化学研究所多細胞システム形成研究センター（CDB）

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Category	CDBセミナー
Date and Time	2006-11-10 17:00 - 18:00
Venue	Auditorium C1F
Speaker	Syu-ichi Hirai
Affiliation	Department of Molecular Biology, Yokohama City University Gradutate School of Medical Science
Title	JNK activator DLK regulates axon growth and neuronal migration in the developing cerebral cortex
Host	Shinichi Aizawa
Summary	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 DCX, 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.