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Publication : α2-chimaerin controls neuronal migration and functioning of the cerebral cortex through CRMP-2.

First Author  Ip JP Year  2011
Journal  Nat Neurosci Volume  15
Issue  1 Pages  39-47
PubMed ID  22138645 Mgi Jnum  J:180317
Mgi Id  MGI:5306092 Doi  10.1038/nn.2972
Citation  Ip JP, et al. (2012) alpha2-chimaerin controls neuronal migration and functioning of the cerebral cortex through CRMP-2. Nat Neurosci 15(1):39-47
abstractText  Disrupted cortical neuronal migration is associated with epileptic seizures and developmental delay. However, the molecular mechanism by which disruptions of early cortical development result in neurological symptoms is poorly understood. Here we report alpha2-chimaerin as a key regulator of cortical neuronal migration and function. In utero suppression of alpha2-chimaerin arrested neuronal migration at the multipolar stage, leading to accumulation of ectopic neurons in the subcortical region. Mice with such migration defects showed an imbalance between excitation and inhibition in local cortical circuitry and greater susceptibility to convulsant-induced seizures. We further show that alpha2-chimaerin regulates bipolar transition and neuronal migration through modulating the activity of CRMP-2, a microtubule-associated protein. These findings establish a new alpha2-chimaerin-dependent mechanism underlying neuronal migration and proper functioning of the cerebral cortex and provide insights into the pathogenesis of seizure-related neurodevelopmental disorders.
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