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

Kodai Sasamoto, Jun Nagai, Takeru Nakabayashi, Xiaojuan He, Toshio Ohshima*

*この研究の対応する著者

    研究成果: Article査読

    1 被引用数 (Scopus)

    抄録

    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.

    本文言語English
    ジャーナルDevelopmental Neurobiology
    DOI
    出版ステータスAccepted/In press - 2016

    ASJC Scopus subject areas

    • 細胞および分子神経科学
    • 発達神経科学

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