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Publication : Cdk5 is required for the positioning and survival of GABAergic neurons in developing mouse striatum.

First Author  Sasamoto K Year  2017
Journal  Dev Neurobiol Volume  77
Issue  4 Pages  483-492
PubMed ID  27480591 Mgi Jnum  J:261117
Mgi Id  MGI:6154500 Doi  10.1002/dneu.22424
Citation  Sasamoto K, et al. (2017) Cdk5 is required for the positioning and survival of GABAergic neurons in developing mouse striatum. Dev Neurobiol 77(4):483-492
abstractText  Cyclin-dependent kinase 5 (Cdk5) is a serine/threonine kinase, and its activity is dependent upon an association with a neuron-specific activating subunit. It was previously reported that Cdk5(-/-) mice exhibit perinatal lethality and defective neuronal positioning. In this study, they focused on the analysis of neuronal positioning of GABAergic neurons in the forebrain. Defective formation of the ventral striatum, nucleus accumbens, and olfactory tubercles was found in Cdk5(-/-) embryos. To further study this abnormal development, we generated and analyzed Dlx5/6-Cre p35 conditional KO (cKO); p39(-/-) mice in which forebrain GABAergic neurons have lost their Cdk5 kinase activity. Defective formation of the nucleus accumbens and olfactory tubercles as well as neuronal loss in the striatum of Dlx5/6-Cre p35cKO; p39(-/-) mice was found. Elevated levels of phosphorylated JNK were observed in neonatal striatal samples from Dlx5/6-Cre p35cKO; p39(-/-) mice, suggestive of neuronal death. These results indicate that Cdk5 is required for the formation of the ventral striatum in a cell-autonomous manner, and loss of the kinase activity of Cdk5 causes GABAergic neuronal death in the developing mouse forebrain. (c) 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 419-437, 2017.
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