Get access

Effects of FAK ablation on cerebellar foliation, Bergmann glia positioning and climbing fiber territory on Purkinje cells

Authors

  • Fumihiro Watanabe,

    1. Department of Molecular Neurobiology and Pharmacology, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan
    Search for more papers by this author
    • *

      F.W. and T.M. contributed equally to this work.

  • Taisuke Miyazaki,

    1. Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan
    Search for more papers by this author
    • *

      F.W. and T.M. contributed equally to this work.

  • Tomonori Takeuchi,

    1. Department of Molecular Neurobiology and Pharmacology, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan
    Search for more papers by this author
  • Masahiro Fukaya,

    1. Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan
    Search for more papers by this author
  • Takanori Nomura,

    1. Department of Molecular Neurobiology and Pharmacology, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan
    Search for more papers by this author
  • Shigeru Noguchi,

    1. Pharmaceutical Development Department, Meiji Dairies Corporation, 540 Naruda Odawara, Kanagawa 250-0862, Japan
    Search for more papers by this author
  • Hisashi Mori,

    1. Department of Molecular Neurobiology and Pharmacology, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan
    Search for more papers by this author
    • Present address: Department of Molecular Neuroscience, Graduate School of Medicine, University of Toyama, Toyama 930-0194, Japan.

  • Kenji Sakimura,

    1. Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan
    Search for more papers by this author
  • Masahiko Watanabe,

    1. Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan
    Search for more papers by this author
  • Masayoshi Mishina

    1. Department of Molecular Neurobiology and Pharmacology, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan
    Search for more papers by this author

Dr M. Watanabe and Dr M. Mishina, as above.
E-mail: watamasa@med.hokudai.ac.jp and mishina@m.u-tokyo.ac.jp

Abstract

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that is widely expressed in the brain, and plays key roles in various cellular processes in response to both extracellular and intracellular stimuli. Here, we explored the role of FAK in cerebellar development. In the mouse cerebellum, FAK was found to be distributed as tiny cytoplasmic aggregates in various neuronal and glial elements, including Purkinje cells (PCs), Bergmann glia (BG), parallel fiber (PF)-terminals and climbing fiber (CF)-terminals. The neuron/glia-specific ablation of FAK impaired cerebellar foliation, such as variable decreases in foliation sizes and the lack of intercrural and precentral fissures. Some of the BG cells became situated ectopically in the molecular layer. Furthermore, the FAK ablation altered the innervation territories of CFs and PFs on PCs. CF innervation regressed to the basal portion of proximal dendrites and somata, whereas ectopic spines protruded from proximal dendrites and PFs expanded their territory by innervating the ectopic spines. Furthermore, the persistence of surplus CFs innervating PC somata caused multiple innervation. When FAK was selectively ablated in PCs, diminished dendritic innervation and persistent somatic innervation by CFs were observed, whereas cerebellar foliation and cell positioning of BG were normally retained. These results suggest that FAK in various neuronal and glial elements is required for the formation of normal histoarchitecture and cytoarchitecture in the cerebellum, and for the construction of proper innervation territory and synaptic wiring in PCs.

Ancillary