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Publication : LKB1 regulates neuronal migration and neuronal differentiation in the developing neocortex through centrosomal positioning.

First Author  Asada N Year  2007
Journal  J Neurosci Volume  27
Issue  43 Pages  11769-75
PubMed ID  17959818 Mgi Jnum  J:127036
Mgi Id  MGI:3762698 Doi  10.1523/JNEUROSCI.1938-07.2007
Citation  Asada N, et al. (2007) LKB1 regulates neuronal migration and neuronal differentiation in the developing neocortex through centrosomal positioning. J Neurosci 27(43):11769-75
abstractText  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.
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