Laboratory for Molecular Neurogenesis
Laboratory Head
Teiichi FURUICHI (Ph.D.)
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 projects.
Project 1: 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.
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 secretion [BDNF & catecholamine secretion], very-KIND (MAP2-binding RasGEF), p130Cas (an adaptor protein for the Src tyrosine kinase signaling pathway), Cupidin/Homer2 (a scaffold protein in postsynaptic density), Opalin (a sialylglycoprotein in the central myelin loop membrane), and PLD4 (microglia-specific phospholipase D member, without PLD activity).
Project 3: 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
- 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
- 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 (a scaffold protein in postsynaptic density), Opalin (a sialylglycoprotein in the central myelin loop membrane), and PLD4 (a microglia-specific phospholipase D member without PLD activity)
- Systematization of brain development gene expression: Cerebellar development transcriptome database (CDT-DB) project
- RIKEN Brain Science Institute Website_Laboratories Page
- Individual Website Laboratory Page
- Cerebellar Development Transcriptome Database (CDT-DB) Page
- Decemver 21, 2010
- CAPS2 enhances secretion of neurotrophic factor BDNF and ensures normal development of brain circuit.
- March 23, 2007
- Molecular Neurogenesis of BSI disclosed that gene impairment in CADPS2, which regulates the secretion of neurotrophic factor for neuronal growth and differentiation, was highly associated with autism onset in mice.
- Shinoda, Y., Sadakata, T., Nakao, K., Katoh-Semba, R., Kinameri, E., Furuya, A., Yanagawa, Y., Hirase, H., and Furuichi, T.
"Calcium-dependent activator protein for secretion 2 (CAPS2) promotes BDNF secretion and is critical for the development of GABAergic interneuron network."
Proc. Natl. Acad. Sci. U.S.A. 108:373-378 (2011). - Sadakata, T., Shinoda, Y., Sekine, Y., Saruta, C., Itakura, M., Takahashi, M., and Furuichi, T.
"Interaction of CAPS1 with the class II Arf small GTPases is required for dense-core vesicle trafficking in the trans-Golgi network."
J. Biol. Chem. 285:38710-38719 (2010). - Yoshikawa, F., Banno, Y., Otani, Y., Yamaguchi, Y., Nagakura-Takagi, Y., Morita, N., Sato, Y., Saruta, C., Nishibe, H., Sadakata, T., Shinoda, Y., Hayashi, K., Mishima, Y., Baba, H., and Furuichi, T.
"Phospholipase D family member 4, a transmembrane glycoprotein with no phospholipase D activity, expression in spleen and early postnatal microglia."
PLoS ONE 5 (11):e13932 (2010). - 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). - 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). - 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). - 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). - 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). - Shiraishi-Yamaguchi, Y. and Furuichi, T.
"The Homer family proteins."
Genome Biology 8:206.1-206.12 (2007) - 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).