Cyclin-dependent kinase 5 is required for normal cerebellar development

A. Kumazawa, N. Mita, M. Hirasawa, T. Adachi, H. Suzuki, N. Shafeghat, A. B. Kulkarni, K. Mikoshiba, Takafumi Inoue, Toshio Ohshima

    Research output: Contribution to journalArticle

    18 Citations (Scopus)

    Abstract

    Cyclin-dependent kinase 5 (Cdk5) is a serine/threonine kinase, and its kinase activity is dependent upon its association with either of the activating subunits p35 or p39, which are mainly expressed in neurons. We previously reported that Cdk5 knockout (KO) mice exhibit perinatal lethality, defective neuronal migration, and abnormal positioning of neurons in the facial motor nucleus and inferior olive in the hindbrain and Purkinje cells (PCs) in the cerebellum. In this study, we focused on the analysis of the role of Cdk5 in cerebellar development. For this purpose we generated midbrain-hindbrain-specific Cdk5 conditional knockout (MHB-Cdk5 KO) mice because the cerebellum develops postnatally, whereas Cdk5 KO mice die perinatally. Histological analysis of the MHB-Cdk5 KO mice revealed a significant size reduction of the cerebellum. In addition, profound disturbance of inward migration of granule cells (GC) was observed in the developing cerebellum. A normal dendritic development of the Purkinje cells (PCs) was disturbed in MHB-Cdk5 KO mice. Cultured Cdk5-null PCs showed similar dendritic abnormalities. These results indicate that Cdk5/p35 plays an important role in neuronal migration of PCs and GCs and dendrite formation of PCs in cerebellar development.

    Original languageEnglish
    Pages (from-to)97-105
    Number of pages9
    JournalMolecular and Cellular Neuroscience
    Volume52
    DOIs
    Publication statusPublished - 2013 Jan

    Fingerprint

    Cyclin-Dependent Kinase 5
    Purkinje Cells
    Rhombencephalon
    Knockout Mice
    Cerebellum
    Mesencephalon
    Neurons
    Null Lymphocytes
    Protein-Serine-Threonine Kinases
    Dendrites
    Cell Movement
    Phosphotransferases

    Keywords

    • Cdk5
    • Conditional KO
    • Dendrite
    • Midbrain-hindbrain
    • Neuronal migration

    ASJC Scopus subject areas

    • Molecular Biology
    • Cellular and Molecular Neuroscience
    • Cell Biology

    Cite this

    Cyclin-dependent kinase 5 is required for normal cerebellar development. / Kumazawa, A.; Mita, N.; Hirasawa, M.; Adachi, T.; Suzuki, H.; Shafeghat, N.; Kulkarni, A. B.; Mikoshiba, K.; Inoue, Takafumi; Ohshima, Toshio.

    In: Molecular and Cellular Neuroscience, Vol. 52, 01.2013, p. 97-105.

    Research output: Contribution to journalArticle

    Kumazawa, A, Mita, N, Hirasawa, M, Adachi, T, Suzuki, H, Shafeghat, N, Kulkarni, AB, Mikoshiba, K, Inoue, T & Ohshima, T 2013, 'Cyclin-dependent kinase 5 is required for normal cerebellar development', Molecular and Cellular Neuroscience, vol. 52, pp. 97-105. https://doi.org/10.1016/j.mcn.2012.10.007
    Kumazawa, A. ; Mita, N. ; Hirasawa, M. ; Adachi, T. ; Suzuki, H. ; Shafeghat, N. ; Kulkarni, A. B. ; Mikoshiba, K. ; Inoue, Takafumi ; Ohshima, Toshio. / Cyclin-dependent kinase 5 is required for normal cerebellar development. In: Molecular and Cellular Neuroscience. 2013 ; Vol. 52. pp. 97-105.
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