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Disease Mechanism Research Core

Laboratory for Molecular Neurogenesis

Tei-ichi FURUICHI, Ph.D.
Tei-ichi FURUICHI, Ph.D.
Laboratory Head
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Laboratory websiteLaboratory website
Laboratory websiteLaboratory website (CDT-DB)
PublicationMain Publications at RIKEN

Research Areas

Our laboratory aims to elucidate the molecular mechanisms underlying normal brain development and its disorders by systematic identification and functional analyses of brain development genes. We namely performed three research subjects.

Project 1: Systematization of brain development gene expression
We characterize the transcriptomic basis of mouse cerebellar circuit development by generating the Cerebellar Development Transcriptome Database (CDT-DB). *CDT-DB http://www.cdtdb.brain.riken.jp

Project 2: Molecular mechanisms of neural circuit development
We clarify the molecular mechanisms of neural circuit development (neuronal development and survival, axon and dendrite growth, development of spine morphology and function, and development of myelin loops) by analyzing the functional roles of brain development genes identified by data mining of the CDT-DB.　We focus on functional analyses of five genes: CAPS2 (a regulator for dense-core vesicle seceretion [BDNF & catecholamine secretion], very-KIND (MAP2-binding RasGEF), p130Cas (an adaptor protein for the Src tyrosine kinase signaling pathway), Cupidin/Homer2 (ascaffold protein in postsynaptic density), and Opalin (a sialylglycoprotein in the central myelin loop membrane).

Project 3: Molecular mechanism underlying susceptibility to developmental disorders
We analyze the implication of Ca2+-dependent activator protein for secretion 2 (CAPS2) in susceptibility to autism, a developmental disorder.


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Top: Cerebellar circuit and Cerebellar Development Transcriptome Database (CDT-DB). Our CDT-DB is an online database that contains spatio-temporal gene expression information in relation to the postnatal developmental stages of mouse cerebellum, and also has various search functions.
Bottom left: Cupidin is composed of the N-terminal domain for binding to its targets (mGluR1α /5, IP3R, Shank, Drebrin, etc.) and the C-terminal domain for self-assembly, and regulates crosslinks of these postsynaptic targets and the spine morphology. In the cerebellum, Cupidin is localized in postsynapses of granule cells (GC) connecting mossy fiber terminals (mft).
Bottom right: CAPS2 regulates Ca2+-dependent secretion of neurotrophins (NT-3 and BDNF) and is involved in neuronal differentiation and survival. In the cerebellum, CAPS2 is primarily concentrated at vesicular structures within parallel fiber (PF) terminals connecting Purkinje cell (PC) spines.

Research Subjects

  1. Systematization of brain development gene expression: Cerebellar development transcriptome database (CDT-DB) project
  2. Molecular mechanisms of neural circuit development: Functional analyses of CAPS2 (a regulator for dense-core vesicle seceretion [BDNF & catecholamine secretion], very-KIND (MAP2-binding RasGEF), p130Cas (an adaptor protein for the Src tyrosine kinase signaling pathway), Cupidin/Homer2 (ascaffold protein in postsynaptic density), and Opalin (a sialylglycoprotein in the central myelin loop membrane)
  3. Molecular mechanism underlying susceptibility to developmental disorders: Analysis and implication of Ca2+-dependent activator protein for secretion 2 (CAPS2) in susceptibility to autism, a developmental disorder

Selected Publications

  1. Sadakata, T., Washida, M., Iwayama, Y., Shoji, S., Sato, Y., Ohkura, T., Kato-Semba, R., Nakajima, M., Sekine, Y., Tanaka, M., Nakamura, K., Iwata, Y., Tsuchiya, K.J., Mori, N., Detera-Wadleigh, S.D., Ichikawa, H., Itohara, S., Yoshikawa, T., and Furuichi, T.:
    "Autistic-like phenotypes in CADPS2/CAPS2 knockout mice and aberrant CADPS2 splicing in autistic patients."
    J. Clin. Invest. 117:931-943 (2007).
  2. Sadakata, T., Kakegawa, W., Mizoguchi, A., Washida, M., Katoh-Semba, R., Shutoh, F., Okamoto, T., Nakashima, H., Kimura, K., Tanaka, M., Sekine, Y., Itohara, S., Yuzaki, M., Nagao, S., and Furuichi, T.:
    "Impaired cerebellar development and function in mice lacking CAPS2, a protein involved in neurotrophin release."
    J. Neurosci. 27:2472-2482 (2007).
  3. Sadakata, T., and Furuichi, T.:
    "Developmentally-regulated Ca2+-dependent activator protein for secretion 2 (CAPS2) is involved in BDNF release and is associated with autism susceptibility."
    The Cerebellum (2009) in press.
  4. Sato, A., Sekine, Y., Saruta, C., Nishibe, H., Morita, N., Sato, Y., Sadakata, T., Shinoda, Y., Kojima, T., and Furuichi, T.:
    "Cerebellar development transcriptome (CDT-DB): profiling of spatio-temporal gene expression during the postnatal development of mouse cerebellum."
    Neural Networks 21:1056-1069 (2008).
  5. Yoshikawa, F., Sato, Y., Tohyama, K., Akagi, T., Hashikawa, T., Nagakura-Takagi, Y., Sekine, Y., Morita, N., Baba, H., Suzuki, Y., Sugano, S., Sato, A., and Furuichi, T.:
    "Opalin, a transmembrane sialylglycoprotein located in the CNS myelin paranodal loop membrane."
    J. Biol. Chem. 283:20830-20840 (2008).
  6. Mizutani, A., Kuroda, Y., Futatsugi, A., Furuichi, T., and Mikoshiba, K.:
    "Phosphorylation of Homer3 by calcium/calmodulin-dependent kinase II regulates a coupling state of its target molecules in Purkinje cells."
    J. Neurosci. 28:5369-5382 (2008).
  7. Shiraishi-Yamaguchi, Y., and Furuichi, T.:
    "The Homer family proteins."
    Genome Biology 8:206.1-206.12 (2007)
  8. Kuwajima, M., Dehoff, MH., Furuichi, T., Worley, PF., Hall, RA., and Smith, Y.:
    "Localization and expression of group I metabotropic glutamate receptors in the mouse striatum, globus pallidus, and subthalamic nucleus: regulatory effects of MPTP treatment and constitutive Homer deletion."
    J. Neurosci. 27:6249-6260 (2007).
  9. Huang, J., Furuya, A., and Furuichi, T.:
    "Very-KIND, a KIND domain-containing RasGEF, controls dendrite growth by linking Ras small GTPases and MAP2."
    J. Cell Biol. 179:539-552 (2007).
  10. Huang, JH., Sakai, R., and Furuichi, T.:
    "The docking protein Cas links tyrosine phosphorylation signaling to elongation of cerebellar granule cell axons."
    Mol. Biol. Cell. 17:3187-3196 (2006).

Main Publications at RIKEN


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