嗅球の誘導の分子機構

• Project/Area Number: 10220208
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The University of Tokyo (1999-2003); The Institute of Physical and Chemical Research (1998)
• Principal Investigator: 山口 正洋 (2002-2003) 東京大学, 大学院・医学系研究科, 講師 (60313102); 森 憲作 (1998-2001) 東京大学, 大学院・医学系研究科, 教授 (60008563)
• Co-Investigator(Kenkyū-buntansha): 長尾 伯 東京大学, 大学院・医学系研究科, 助手 (50281647) ; 森 憲作 東京大学, 大学院・医学系研究科, 教授 (60008563) ; 山口 正洋 東京大学, 大学院・医学系研究科, 講師 (60313102) ; 杉野 英彦 理化学研究所, 機能分子研究チーム, 研究員 (70270577) ; 中川 リリア 理化学研究所, 機能分子研究チーム, 研究員 (80300888)
• Project Period (FY): 1998 – 2003
• Project Status: Completed (Fiscal Year 2003)
• Budget Amount: ¥50,000,000 (Direct Cost: ¥50,000,000); Fiscal Year 2003: ¥8,000,000 (Direct Cost: ¥8,000,000); Fiscal Year 2002: ¥8,000,000 (Direct Cost: ¥8,000,000); Fiscal Year 2001: ¥9,700,000 (Direct Cost: ¥9,700,000); Fiscal Year 2000: ¥9,600,000 (Direct Cost: ¥9,600,000); Fiscal Year 1999: ¥7,200,000 (Direct Cost: ¥7,200,000); Fiscal Year 1998: ¥7,500,000 (Direct Cost: ¥7,500,000)
• Keywords: 嗅球 / 細胞接着分子 / 顆粒細胞 / 神経新生 / 神経回路 / 匂い地図 / Sema3A / 軸索ガイダンス / セマフォリン / ニューロピリン / 糸球 / 副嗅球 / フェロモン地図 / 内因性信号の光学測定 / 匂いマップ / フェロモンマップ / 感覚細胞 / 誘導 / OCAM / 神経幹細胞 / ニューロンの新生

Research Abstract

1.嗅球神経回路の誘導および形成に関わる機能分子の探索
プロテオミクス解析で得たマウス嗅球の嗅神経層、糸球体層、外叢状層に存在する細胞膜蛋白分子群の発現パターンをスクリーニングし、細胞外にロイシンリッチリピートを持つ接着分子が嗅球の一部の介在神経細胞に発現していることを見出した。この分子は介在神経細胞の樹状突起上に豊富に分布しており、その樹状突起は外叢状層のなかの特定の層で多くの分枝を作っていた。また、この分子発現は個体の発達過程において、シナプス形成の時期に強く誘導されていた。以上より、この分子は嗅球内の特定の神経回路の形成に関わる重要な分子であると考えられた。
2.入力依存的な嗅球神経細胞および嗅球神経回路の誘導メカニズムの解析
嗅球では成体においても介在神経細胞(顆粒細胞および傍糸球細胞)が新生し、神経回路に組み込まれている。前年度に、新生顆粒細胞の生存は匂い入力の有無で調節されていること、新生顆粒細胞の生存が匂い入力に左右される特定の時期(臨界期)が存在することを示した。本年度は、匂い入力遮断で新生顆粒細胞が除去される際にはアポトーシス経路の活性化を伴っていること、アポトーシスに至る顆粒細胞は生まれてからある一定の日数を経た特定の細胞集団であることを見出した。さらに、匂い入力依存的な新生顆粒細胞の生存の臨界期は、薬剤投与によっても再現できることを見出した。これらの観察により、匂い入力依存的な嗅球新生神経細胞の生存調節および嗅球神経回路の再構成の分子メカニズムの、鍵となる分子を知ることができた。

Research Products

• [Publications] Yoshida, N.et al.: "Decrease in expression of alpha 5 beta 1 integrin during neuronal differentiation of cortical progenitor cells"Experimental Cell Research. 287. 262-271 (2003)
• [Publications] Fukuda, S.et al.: "Two distinct subpopulations of nestin-positive cells in adult mouse dentate gyrus"Journal of Neuroscience. 23. 9357-9366 (2003)
• [Publications] Kronenberg, G.et al.: "Subpopulations of proliferating cells of the adult hippocampus respond differently to physiologic neurogenic stimuli"Journal of Comparative Neurology. 467. 455-463 (2003)
• [Publications] Nagayama, S.et al.: "Mitral and tufted cells differ in the decording manner of odor maps in the rat olfactory bulb"Journal of Neurophysiology. In press.
• [Publications] Inaki, K., et al.: "Molecular-feature domains with posterodorsal-anteroventral polarity in the symmetrical sensory maps of the mouse olfactory bulb : mapping of odourant-induced Zif268 expression"European Journal of Neuroscience. 15(10). 1563-1574 (2002)
• [Publications] Sugitani, Y., et al.: "Brn-1 and Brn-2 share crucial roles in the production and positioning of mouse neocortical neurons"Genes and Development. 16(14). 1760-1765 (2002)
• [Publications] Nagao, H., et al.: "Grouping and representation of odorant receptors in domains of the olfactory bulb sensory map"Microscopy Research and Technique. 58(3). 168-175 (2003)
• [Publications] Kempermann, G., et al.: "Early determination and long-term persistence of adult-generated new neurons in the hippocampus of mice"Development. 130(2). 391-399
• [Publications] Taniguchi, M., et al.: "Distorted odor maps in the olfactory bulb of semaphorin 3A-deficient mice"Journal of Neuroscience. 23(4). 1390-1397 (2003)
• [Publications] Treloar, H.B., et al.: "Inverse expression of OCAM in a subset of olfactory axons and a subset of mitral/tufted cells in the developing rat olfactory bulb"Journal of Comparative Neurology. (in press).
• [Publications] Mori, K.: "Grouping of odourant receptors : odour maps in the mammalian olfactory bulb"Biochem.Soc.Trans.. 31. 134-136 (2003)
• [Publications] Filipov, V., et al.: "Subpopulation of nestin-expressing progenitor cells in the adult murine hippocampus shows electrophysiological and morphological characteristics of astrocytes"Molecular and Cellular Neuroscience. (in press).
• [Publications] Yoshihara Y., Nagao H., Mori, K.: "Sniffing out odors with multiple dendrites"Science. 291巻. 835-837 (2001)
• [Publications] Tatsura H., Nagao, H., Tamada, A., Sasaki, S., Kohri, K., Mori, K.: "Developing germ cells in mouse testis express pheromone receptors"FEBS letters. 488巻. 139-144 (2001)
• [Publications] Mizuno T., Kawasaki, M., Nakahira, M., Kagamiyama, H., et al.: "Molecular diversity in zebrafish NCAM family : three members with distinct VASE usage and distinct localization"Molecular and Cellular Neuroscience. 18巻. 119-130 (2001)
• [Publications] Sawamoto K, Yamamoto A, Kawaguchi A, Yamaguchi M, Mori K, et al.: "Direct isolation of committed neuronal progenitor cells from transgenic mice coexpressing spectrally distinct fluorescent proteins regulated by stage-snecific neural promoters"J Neurosci Res.. 65巻. 220-227 (2001)
• [Publications] Sawamoto K, Nakano N, Kakishita K, Ogawa Y, Toyama Y, et al.: "Generation of dopaminergic neurons in the adult brain from mesencephalic precursor cells labeled with a nestin-GFP transgene"J Neurosci.. 21巻. 3895-3903 (2001)
• [Publications] von Campenhansen H.,& Mori,K.: "Convergence of segregated neuronal pathways from the accessory olfactory bulb to the cortex in the mouse"Eur.J.of Neuroscience. 12巻. 33-46 (2000)
• [Publications] Uchida,N., 他: "Color Maps in the mammalian olfactory bulb : Domain Organization and colorant structural features"Nature Neuroscience. 3巻. 1035-1043 (2000)
• [Publications] Nagao,H., 他: "Two mirror-image sensory maps with domain organization in the mouse main olfactory bulb"Neuro Report. 11巻. 3023-3027 (2000)
• [Publications] Yamaguchi,M., 他: "Visualization of neurogenesis in the central nervous system using nestin promotor-GFP transgenic mice"Neuro Report. 11巻. 1991-1996 (2000)
• [Publications] Mori,K., 他: "Zonal organization of the mammalian main and accessory olfactory systems"Phil.Trans.R.Soc.Lond.B.. 355巻. 1801-1802 (2000)
• [Publications] Yoshihara,Y.,Nagao,H,& Mori,K.: "Snifting out colors with multiple dendrites"Science. 29巻. 835-837 (2001)
• [Publications] Mori, K. 他: "The olfactory bulb : coding and processing of odor molecule information"Science. 286. 711-715 (1999)
• [Publications] Yoshihara, Y. 他: "A genetic approach to visualization of multi-synaptic neuronal pathways using plant lectin transgene"Neuron. 22. 33-41 (1999)
• [Publications] Kashiwadani, H. 他: "Synchronized oscillatory discharges of mitral/tufted cells with different molecular receptive ranges in the rabbit olfactory bulb"J. Nuerophysiology. 82. 1786-1792 (1999)
• [Publications] Von Campenhausen, H. 他: "Convergence of segregated pheromonal patients from the accessory olfactory bulb to the cortex"Europian Journal of Nueroscience. (印刷中). (2000)
• [Publications] Mizuno, T. 他: "Neuronal adhesion molecule telencephalin induces rapid cell spreading of microglia"Brain Research. 849. 58-66 (1999)
• [Publications] Arii, N. 他: "Development of telencephalin in human cerebrum"Microscop. Res. Tech.. 46. 18-23 (1999)
• [Publications] Tamada, A.他: "Dendrite-associated cell adhesion molecule, telencephalin, promotes neurite outgrowth in mouse embryo." Neuroscience Letters. 240・3. 163-166 (1998)
• [Publications] Benson, D.他: "Polarized distribution and cell-type specific localization of telencephalin, an intercellular adhesion molecules." Journal of Neuroscience Research. 52. 43-53 (1998)
• [Publications] Sakurai, E.他: "Involvement of dendritic adhesion molecule telencephalin in hippocampal long-term potentiation." Neuro Report. 9. 881-886 (1998)
• [Publications] Mori, K.他: "Computation of molecular information in mammalian olfactory systems." Network:Computationin Neural Systems. 9・4. R79-R102 (1998)
• [Publications] Yoshihara, Y.他: "A genetic approach to visualization of multi-synaptic neural pathways using plant lectin transgene." Neuron. 22. 33-41 (1999)