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Publication : Differential roles of cyclin-dependent kinase 5 in tangential and radial migration of cerebellar granule cells.

First Author  Umeshima H Year  2013
Journal  Mol Cell Neurosci Volume  52
Pages  62-72 PubMed ID  22995860
Mgi Jnum  J:203674 Mgi Id  MGI:5528453
Doi  10.1016/j.mcn.2012.08.005 Citation  Umeshima H, et al. (2013) Differential roles of cyclin-dependent kinase 5 in tangential and radial migration of cerebellar granule cells. Mol Cell Neurosci 52:62-72
abstractText  The cerebellar granule cell is a unique neuron which undergoes tangential migration along axonal tracts and radial migration along glial fibers sequentially during postnatal development. Little is known about molecular bases of the differential kinetics of tangential and radial migration. Here we developed a time-lapse imaging assay for tangential migration of cerebellar granule cells, and investigated comparative contributions of cyclin-dependent kinase 5 (CDK5), a key regulator of neuronal migration, in tangential and radial migration of granule cells in vivo and in organotypic cultures. Overexpression of a dominant-negative form of CDK5 severely disrupted cell morphology and somal movement during radial migration, while it only moderately affected tangential migration. Dominant-negative inhibition of CDK5 induced formation of ectopic radial processes in granule cells in vivo which aberrantly elongated into the white matter in the cerebellum. Live imaging of granule cell migration in cerebellar slices revealed that CDK5 regulates not only nuclear migration but also centrosome movement during radial migration. These findings suggest a mode-specific function of CDK5 in neuronal migration.
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