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(In Japanese)脳を知る 脳神経系を構成する細胞の多様性の形成機構

Research report code R990004306
Posted date Feb 6, 2001
  • (In Japanese)岡野 栄之
  • (In Japanese)大阪大学大学院医学系研究科
Research organization
  • (In Japanese)大阪大学大学院医学系研究科
Report name (In Japanese)脳を知る 脳神経系を構成する細胞の多様性の形成機構
Technology summary (In Japanese)この研究は、脳・神経系の高次機能の基盤となる細胞の多様性の形成機構につき、既存技術の高度な統合駆使と、独創的な新技術開発をも行いつつ、戦略的に解明することを目指すものである。アプローチとして、神経発生の初期過程を制御する遺伝子産物が無脊椎動物から脊椎動物まで広く保存されていることを利用し、ショウジョウバエの神経発生過程における細胞の運命決定を制御する遺伝子産物を同定・解析することを出発点として、これで同定された遺伝子産物の哺乳類相同分子を単離してその機能解析を行って、哺乳類神経系を構成する細胞の多様性形成メカニズムを追求せんとした。また、得た基本的知見の治療法開発などへの応用も将来視野に据えた。これら目的を達成すべく、神経幹細胞やNotch情報伝達系や線虫など、8項目のプロジェクトを遂行し、幾つかの成果を上げている。これらプロジェクトは何れも神経発生過程での細胞運命決定や神経機能形成の関する機能解析と応用に関するものである。

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Research field
  • Research methods in biological sciences in general
  • Research methods in genetics
  • Gene expression
  • Cell physiology in general
  • Function of cell components
Published papers related (In Japanese)(1)Sawamoto, K., Taguchi, A., Jin, M., Yamada, C. and Okano, H.: Argos induces programmed cell death in the developing Drosophila eye by inhibition of the Ras pathway. Cell Death and Differentiation, 5, 262-270 (1998)
(2)Hamada, S., Senzaki, K., Hamaguchi-Hamada, K., Tabuchi, K., Yamamoto, H., Yamamoto, T., Yoshikawa, S., Okano, H. and Okado, N.: Localization of 5-HT2A receptor in rat cerebral cortex and olfactory system revealed by immunohistochemistry using two antibodies raised in rabbit and chicken. Mol. Brain Res., 54, 199-211 (1998)
(3)Hisahara, S., Shoji, S., Yoshikawa, S., Okano, H. and Miura, M.: Functional expression of bcl-2 family gene in Drosophila cells. J. Cell Sci., 111, 667-673 (1998)
(4)Pincus, D.W., Keyoung, H., Restelli, C., Goodman, R.R., Fraser, R.A.R., Edgar, M., Sakakibara, S., Okano, H., Nedergaard, M. and Goldman, S.A.: FGF2/BDNF-responsive neuronal progenitor cells in the adult human subependyma. Annals of Neurology, 43, 576-585 (1998)
(5)Saito, T., Sawamoto, K., Okano, H., Anderson, D.J., and Mikoshiba, K.: Mammalian BarH homolog is a regulatory switch of proneural genes to establish neuromere identities. Dev. Biol., 199, 216-225 (1998)
(6)Good, P., Yoda, A., Sakakibara, S., Yamamoto, A., Imai, T., Sawa, H., Ikeuchi, T., Tsuji, S., Satoh, H. and Okano, H.: The Human Musashi homolog1 (MSI1) gene encoding the homologue of Musashi/Nrp-1, a neural RNA-binding protein putatively expressed in CNS stem cells and neural progenitor cells. Genomics, 52, 382-384 (1998)
(7)Tabuchi, K. Yoshikawa, S., Yuasa, Y., Sawamoto, K. and Okano, H.: Isolation and characterization of a novel Drosophila paired-like homeobox gene related to Caenorhabditis elegans unc-4 and expressed in the subsets of developing neurons and epidermis. Neurosci. Lett., 257, 49-52 (1998)
(8)Kanuka, H., Hisahara, S., Sawamoto, K., Shoji, S., Okano, H. and Miura, M.: Execution of programmed cell death in Drosophila by C. elegans Cell death gene ced-4. Proc. Natl. Acad. Sci. USA, 96, 145-150 (1999)
(9)Yoshihara, Y., Mizuno, T., Nakahira, M., Kawasaki, M., Watanabe, Y., Kagamiyama, H., Jishage, K., Ueda, O., Suzuki, H., Tabuchi, K., Sawamoto, K., Okano, H., Noda, T. and Mori, K.: Multi-synaptic neural pathways visualized with plant lectin transgenes. Neuron, 22, 33-41 (1999)
(10)Umemori, H., Kadowaki, Y., Hirosawa, K., Okano, H. and Yamamoto, T.: Stimulation of myelin basic protein gene transcription by Fyn tyrosine kinase for myelination. J. Neurosci., 19, 1393-1397 (1999)
(11)Sawamoto, K., Yamada, C., Kisida, S., Hirota, Y. Kikuchi, Y. and Okano, H.: Ectopic expression of mutationally-activated Ral GTPase inhibits cell shape changes during Drosophila eye development. Oncogene, 18, 1967-1974 (1999)
(12)Nagata, T., Kanno, R., Kurihara, Y., Uesugi, S., Imai, T., Sakakibara, S., Okano, H. and Katahira, M.: Structure, backbone dynamics and interation with RNA of RNA-binding domain of a mouse neural RNA-binding protein, Musashi-1. J. Mol. Biol., 287, 314-330 (1999)
(13)Araki, T., Saruta, T., Okano, H. and Miura, M.: Caspase activity is required for nephrogenesis in the developing mouse metanephros. Exp. Cell Res., 248, 423-429 (1999)
(14)Nakamura, M., Okano, H., Blendy, J. and Montell, C.: MUSASHI, a neural RNA-binding protein required for Drosophila adult external sensory organ development. Neuron 13, 67-81 (1994)
(15)Sakakibara, S., Imai, T., Aruga, J., Nakajima, K., Yasutomi, D., Nagata, T., Kurihara, Y., Uesugi, S., Miyata, T., Ogawa, M. Mikoshiba, K. and Okano. H. : Mouse-Musashi-1, a Neural RNA-Binding Protein Highly Enriched in the Mammalian CNS Stem Cell. Dev. Biol. 176, 230-242 (1996)
(16)Sakakibara, S. and Okano, H.: Expression of neural RNA-binding proteins in the post-natal CNS: Implication of their roles in neural and glial cells development. J. Neurosci. 17, 8300-8312 (1997)
(17)Pincus, D.W., Keyoung, H., Restelli, C., Goodman, R.R., Fraser, R.A.R., Edgar, M., Sakakibara, S., Okano, H., Nedergaard, M. and Goldman, S.A.: FGF2/BDNF-responsive neuronal progenitor cells in the adult human subependyma. Annals of Neurology 43, 576-585 (1998)
(18)Akamatsu, W., Okano, H.J., Osumi, N., Inoue, T., Nakamura, S., Sakakibara, S., Miura, M., Matsuo, N., Darnell, R.B. and Okano, H.: Mammalian ELAV-like neuronal RNA binding proteins HuB and HuC are involved in the neuronal differentiation of both central and peripheral nervous systems. Proc. Natl. Acad. Sci. USA 96. 9885-9890 (1999)
(19)Kaneko, Y., Sakakibara, S., Imai, T., Suzuki, A., Nakamura, Y., Sawamoto, K., Ogawa, Y., Toyama, Y., Miyata, T. and Okano, H.: Musashi1: an evolutionally conserved marker for CNS progenitor cells including neural stem cells. Dev. Neurosci. 22, 139-153 (2000)
(20)Nakamura, Y., Sakakibara, S., Miyata, T., Ogawa, M., Shimazaki, T., Weiss, S., Kageyama, R. and Okano, H.: the bHLH gene Hes1 as a repressor of neuronal commitment of the CNF stem cells. J. Neurosci. 20, 283-293 (2000)
(21)Roy, N.S., Benraiss, A., Wang, S., Fraser, R.A.R., Goodman, R., Couldwell, W.T., Nedergaard, M., Kawaguchi, A., Okano, H. and Goldman, S.A.: Promoter-targeted selection and isolation of neural progenitor cells from the adult human ventricular zone. J. Neurosci. Res. 59, 321-331 (2000)
(22)Roy, N.S., Wand, S., Jiang, L., Kang J., Restelli, C., Fraser, R.A.R., Couldwell, W.T., Kawaguchi, A., Okano, H. Nedergaard, M. and Goldman, S.A.: In vitro neurogenesis by neural progenitor cells isolated from the adult human hippocampus. Nature Medicine 6, 271-278 (2000)
(23)Ohtani, T., Ishihara, K., Atsumi, T., Nishida, K., Kaneko, Y., Miyata, T., Itoh, S., Narimatsu, M., Maeda, H., Fukada, T., Itoh, M., Okano, H., Hibi, T. and Hirano, T.: Dissection of signaling cascade through gp130 in vivo: Reciprocal roles for STAT3-and SHP2-mediated signals in cytokine and immunoglobulin production. Immunity 12, 95-105 (2000)
(24)Kawaguchi, A., Miyata, T., Sawamoto, K., Takashita, N., Akamatsu, W., Okabe, M., Tano, Y., Goldman, S.A. and Okano, H,: EGFP-mediated live monitoring of stem cell activities in mammalian CNS. Submitted
(25)Sawamoto, K., Yamamoto, A., Kawaguchi, A., Yamaguchi, M., Goldman, S., and Okano, H.,: Dual-color flow cytometric detection of fluorescent proteins driven by the T α1-tubulin and Nestin gene promoters identify neuronal progenitor cells in the mouse embryonic central nervous system. In preparation
(26)Sawamoto, K., Nakao, N., Kakishita, K., Matsushita, M., Ogawa, Y., Yamamoto, A., Miyata, T., Yamaguchi, M., Terashima, T., Kobayashi K., Itakura, T. and Okano, H.,: Direct isolation and characterization of murine mesencephalic progenitor cells and doparminergic neurons. In preparation
Research project
  • Core Research for Evolutional Science and Technology;Understanding the Brain
Information research report
  • (In Japanese)岡野 栄之. 脳を知る 脳神経系を構成する細胞の多様性の形成機構. 戦略的基礎研究推進事業 平成10年度 研究年報,1999. p.601 - 606.