2000 Fiscal Year Annual Research Report

獲得性生体情報の構築・応答ならびにその異常と病態の研究

Research Project

Project/Area Number	12CE2006
Research Category	Grant-in-Aid for COE Research
Research Institution	Kyoto University
Principal Investigator	本庶佑京都大学, 医学研究科, 教授 (80090504)
Co-Investigator(Kenkyū-buntansha)	北徹京都大学, 医学研究科, 教授 (60161460) 湊長博京都大学, 生命科学研究科, 教授 (40137716) 中西重忠京都大学, 生命科学研究科, 教授 (20089105)
Keywords	クラススイッチ / 体細胞突然変異 / AID / PD-1 / PD-L / IMCT法 / パーキンソン / グルタミン酸受容体 / 立体構造
Research Abstract	平成12年度においては、COEプロジェクトとして開始一年目であるにもかかわらず、数々の特筆すべき成果を上げた。第一に、長らく不明であったクラススイッチ制御遺伝子としてAID(Activation-Induced cytidine Deaminase)がマウスとヒトにおいてクラススイッチおよび体細胞突然変異の両方に必須の因子であることを明かにした。第二に、PD-1遺伝子の欠失により拡張型心筋症が起こることを明かにした。また、第三に、代謝型グルタミン酸受容体の結晶化と三次構造を明かにし、構造に基づくdrug designの道を開いた。各グループの具体的成果を下記に記す。本庶は、クラススイッチ及び体細胞突然変異に不可欠な因子としてAIDを同定し、RNAエディティングが遺伝子DNA再構成に必須であるという極めて複雑精緻な免疫制御の機構を明かにした。また、同時にヒトの遺伝病高IgM血症二型がAIDの遺伝子の突然変異であるということをフランスのネッカー病院との共同研究で明かにし、アレルギー等、クラススイッチ制御のメカニズム解明に向けて大きな一歩を踏み出した。さらにはPD-1のリガンドPD-L1ならびにPD-L2を同定し、PD-1の免疫系の負の制御因子であることを確立した。さらにPD-1の遺伝子破壊マウスを作り、これがBALB/c系統のネズミでは拡張型心筋症を発症することを示した(湊との共同研究)。このネズミでは心臓特異的自己抗体を産生し、この沈着により病気が起こることを証明した。湊は、1.ヒトγδT細胞の代表的抗原であるピロ燐酸誘導体を多数合成し、その認識に必要な基本的化学構造を明らかにするとともに、結核菌由来抗原(イソペンテニル・ピロ燐酸)の100倍の比活性を持つ合成抗原を得た。またこの認識には、特定のγδTCR鎖(Vγ1Jγ1.2/Vδ2)とゲノムにコードされるJg1.2配列が必須であることを示した。2.低分子G蛋白Rap1が、インテグリンによる抗原提示細胞との免疫シナプス形成を介したT細胞活性化の主たる制御因子であること、SPA-1遺伝子破壊によるRap1の制御失調により、T細胞応答の異常(アナジーと免疫記憶障害)、自己抗体の出現、顕著な多臓器性随外造血などを伴うヒトの原因不明疾患である骨髄異形成症に酷似した病態が発生することを確認した。北は、動脈硬化の進展、プラークの破綻に重要な役割を担う酸化LDLのマクロファージにおける新たな受容体SR-PSOXをみいだした。この分子のリガンド特異性を明らかにすると共に、実際にヒトの動脈硬化病変にて強く発現されていることをみいだした。また、血小板活性化は動脈硬化の最終段階で血栓形成を惹起し、臨床的な血管障害の発症の成因となる。この分子機構を解明するため、形質膜透過型血小板を用いた顆粒放出測定系を確立し、α顆粒放出にsmall GTPase Rab4が必須であり、細胞質必須因子を精製した結果PKCと同定した。さらに透過型血小板凝集測定系を確立し、small GTPase Rhoが必須であることを見出した。中西は、中西は神経ネットワークの中の特定の神経細胞を除去する方法(IMCT法)を発展させ、1.基底核のコリン作働性神経細胞がドーパミン細胞と協調して運動のバランスを制御している事を明らかにし、パーキンソン病治療の改善にも関わる重要な事実を示した。2.同法を用い、網膜のstarburst細胞が視覚情報の方向選択性とその結果生じる眼振反射を決定しているという神経情報の新しい統合機構を明らかにした。3.興奮性神経伝達の中心的な受容体である代謝型グルタミン酸受容体のグルタミン酸結合部位の結晶化と三次構造を明らかにし、構造に基づくdrug designの道を開いた。

Research Products

(40 results)

All Other

All Publications (40 results)

[Publications] Latchman,Y.,(中略)Nishimura,H.,Honji,T.,Sharpe,A.and Freeman,G.: "PD-L2, a novel B7 homologue, is a second ligand for PD-1 and inhibits T cell activation."Nature Immunol.. (in press). (2001)
[Publications] Muramatsu,M.,and Honjo,T.: "Complex layers of genetic alteration in generation of antibody diversity."Immunol.Today. 22. 66-68 (2001)
[Publications] Nishimura,H.,Tanaka,Y.,Okazaki,T.,Nakatani,K.,Hara,M.,Matsumori,A.,Sasayama,S.,Hiai,H.,Minato,N.,and Honjo,T.: "Autoimmune dilated cardiomyopathy in PD-1 receptor deficient mice."Science. 291. 319-322 (2001)
[Publications] Tanigaki,K.,Nogaki,F.,Takahashi,J.,Tashiro,K.,Kurooka,H.,Honjo,T.: "Notch1 and Notch3 instructively restrict bFGF-responsive multipotent neural progenitor cells to an astroglial fate."Neuron. 29. 45-55 (2001)
[Publications] Watanabe,N.,Ikuta,K.,Fagarasan,S.,Yazumi,S.,Chiba,T.,and Honji,T.: "Migration and differentiation of autoreactive B-1 cells induced by activated γ/δ T cells in antierythrocyte immunoglobulin transgenic mice."J.Exp.Med.. 192. 1577-1586 (2000)
[Publications] Fagarasan,S.,and Honjo,T.: "T-independent immune response : New aspects of B cell biology."Science. 290. 89-92 (2000)
[Publications] Freeman,G.j.,Nishimura,H.,(中略) and Honjo,T.: "Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation."J.Exp.Med.. 192. 1027-1034 (2000)
[Publications] Revy,P.,(中略) Kinoshita,K.,Honjo,T.,Fischer,A.,and Durandy,A.: "Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the Hyper-IgM syndrome (HIGM2)."Cell. 102. 565-575 (2000)
[Publications] Muramatsu,M.,Kinoshita,K.,Fagarasan,S.,Yamada,S.,Shinkai,Y.,and Honjo,T.: "Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing eazyme."Cell. 102. 553-563 (2000)
[Publications] Muto,T.,Muramatsu,M.,Taniwaki,M.,Kinoshita,K.and Honjo,T.: "Isolation, tissue distribution and chromosomal localization of the human activation-induced cytidine deaminase (AID) gene."Genomics. 68. 85-88 (2000)
[Publications] Kamata,T.,Nogaki,F.,Fagarasan,S.,Sakiyama.T.,Kobayashi,I.,Miyawaki,S.,Ikuta,K.,Muso,E.,Yoshida,H.,Sasayama,S.,and Honjo,T.: "Increased frequency of surface IgA-positive plasma cells in the intestinal lamina propria and decreased IgA excretion in hyper IgA (HIGA) mice, a murine model of IgA nephropathy with hyperserum IgA1."J.Immunol.. 165. 1387-1394 (2000)
[Publications] Kurooka,H.and Honjo,T.: "Functional interaction between the mouse Notch1 intracellular region and histone acetyltransferases PCAF and GCN5."J.Biol.Chem.. 275. 17211-17220 (2000)
[Publications] Fagarasan,S.,Shinkura,R.,Kamata,T.,Nogaki,F.,Ikuta,K.,Tashiro,K.,and Honjo,T.: "Alymphoplasia (aly)-type nuclear factor κB-inducing kinase (NIK) causes defects in secondary lymphoid tissue chemokine receptor signaling and homing of peritoneal cells to the gut-associated lymphatic tissue system."J.Exp.Med.. 191. 1477-1486 (2000)
[Publications] Nishimura,H.,Honjo,T.,and Minato,N.: "Facilitation of b selection and modification of positive selection in the thymus of PD-1 deficient mice."J.Exp.Med.. 191. 891-897 (2000)
[Publications] Miyagawa,F.,Tanaka,Y.,Yamashita,S.and Minato,N.: "Essential requirement of antigen presentation by monocyte-lineage cells for the activation of primary human γδ T cells by aminobisphosphonate antigen."J.Immunol. in press. (2001)
[Publications] Nishimura,M.,Tanaka,Y.,Okazaki,T.,Nakatani,K.,Hara,M.,Nishio,R.,Matsumori,A.,Hiai,H.,Minato,N.and Honjo,T.: "Autoimmune dilated cardiomyopathy in PD-1 receptor deficient mice."Science. 291. 319-322 (2001)
[Publications] Suga,K.,Katagiri,K.,Harazaki,M.,Kinashi,T.,Hattori,M.and Minato,N.: "CD98 induces LFA-1-mediated cell adhesion in lymphoid cells via activation of."FEBS Letters.. 489. 249-253 (2001)
[Publications] Kageyama,T.,Nakamura,M.,Matsuo,A.,Yamasaki,Y.,Takakura,Y.,Hashida,M.,Kanai,Y.,Naito,M.,Tsuruo,T.,Minato,N.and Shimohama,S.: "The 4F2hc/LAT1 complex transports L-DOPA across the blood-brain barrier."Brain Res.. 879. 115-121 (2000)
[Publications] Korematsu,S.,Tanaka,Y.,Hosoi,S.,Koyanagi,S.,Yokota,T.,Mikami,B.and Minato,N.: "C8/119S Mutation of Major Mite Allergen Derf-2 Leads to Degenerate Secondary Structure and Molecular Polymerization, and Induces Potent and Exclusive Th1 Cell Differentiation."J.Immunol.. 165. 2895-2902 (2000)
[Publications] Katagiri,K.,Hattori,M.,Minato,N.,Irie,S.,Takatsu,K.,and Kinashi,T.: "Rap1 is a potent activation signal for LFA-1 distinct from PKC and PI3-kinase."Mol.Cell.Biol.. 20. 1956-1969 (2000)
[Publications] Kageyama,T.,Imura,T.,Yamazaki,Y.,Matsuo,A,Minato,N.and Shimohama,S.: "Disttribution of the 4F2 light chain, LAT1, in the mouse brain."Neuroreport. 11. 3663-3666 (2000)
[Publications] Nishimura,H.,Honjo,T.and Minato,N.: "Facillitation of β-selection and modification of positive selection in the thymus of PD-deficient mice."J.Exp.Med.. 191. 891-897
[Publications] Hanyu,M.,Kume,N.,Ikeda,T.,Minami,M.,Kita,T.and Komeda,M.: "VCAM-1 expression precedes macrophage infiltration into subendothelium ofvein grafts interposed into carotid arteries in hypercholesterolemicrabbits-a potential role in vein graft atherosclerosis."Atherosclerosis. (in press). (2001)
[Publications] Morimoto,M.,Kume,N.,Miyamoto,S.,Ueno,Y.,Kataoka,H.,Minami,M.,Hayashida,K.,Hashimoto,N.and Kita,T: "Lysophosphatidylcholine induces Egr-1 expression and activates the core promoter of PDGF-A chain in vascular endothelial cells."Arterioscler.Thromb.Vasc.Biol.. (in press). (2001)
[Publications] Kataoka,H.,Kume,N.,Miyamoto,S.,Minami,M.,Morimoto,M.,Hayashida,K.,Hashimoto,N.and Kita.T.: "Oxidized low density lipoprtoein (Ox-LDL) modulates Bax/Bcl-2 through lectin-like Ox-LDL receptor-1 in vascular smooth muscle cells."Arterioscler.Thromb.Vasc.Biol.. (in press). (2001)
[Publications] Ashida,N.,Arai,H.,Yamasaki,M.and Kita,T.: "Distinct signaling pathways for MCP-1-dependent integrin activation and chemotaxis."J.Biol.Chem.. (in press). (2001)
[Publications] Yamasaki,M.,Arai,H.,Ashida,N.,Ishii,K.and Kita,T.: "Monocyte chemoattractant protein-1 causes differential proline-rich tyrosin kinase 2-mediated signaling in THP-1 cells."Biochemical J.. (in press). (2001)
[Publications] Nakatani,J.,Mizuseki,K.,Tsuda,H.,Nakanishi,S.and Sasai,Y.: "Xenopus Xenf : An early endodermal nuclear factor that is regulated in a pathway distinct from Sox17 and Mix-related gene pathways."Mech.Dev.. 91. 81-89 (2000)
[Publications] Smitt,P.S.,Kinoshita,A.,de Leeuw,B.,Moll,W.,Jaarsma,D.,Henzen-Logmans,S.,Vecht,C.,de Zeeuw,C.,Sekiyama,N.,Nakanishi,S.and Shigemoto,R.: "Hodgkin's disease and ataxia : Passive transfer of autoantibodies that block glutamate receptor mGluR1 causes ataxia in mice."New Eng.J.Med.342 : (2000) 21-27. 342. 21-27 (2000)
[Publications] Takao,M.,Morigiwa,K.,Sasaki,H.,Miyoshi,T.,Shima,T.,Nakanishi,S.,Nagai,K.and Fukuda,Y.: "Impaired behavioral Suppression by light in the mGluR6-deficient mice."Neuroscience. 97. 779-787 (2000)
[Publications] Kishi,M.,Mizuseki,K.,Sasai,N.,Yamazaki,H.,Shiota,K.Nakanishi,S.and Sasai,Y.: "Requirement of Sox2-mediated signaling for differentiation of early Xenopus neuroectoderm."Development. 127. 791-800 (2000)
[Publications] Matsui,M.,Mizuseki,K.,Nakatani,J.,Nakanishi,S.and Sasai,Y.: "Xenopus Kielin : A dorsalizing factor containing multiple chordin-type repeats secreted from the embryonic midline."Proc.Natl.Acad.Sci.USA. 97. 5291-5296 (2000)
[Publications] Spooren,W.P.J.M.,Gasparini,F.,van der Putten,H.,Koller,M.,Nakanishi,S.and Kuhn,R.: "Lack of effect of LY314582 (a group 2 metabotropic glutamate receptor agonist) on phencyclidine-induced locomotor activity in metabotropic glutamate receptor 2 knockout mice."Eur.J.Pharmacol.. 397. R1-R2 (2000)
[Publications] Tomita,K.,Moriyoshi,K.,Nakanishi,S.,Guillmot,F.and Kageyama,R.: "Mammalian achaete-scute and atonal homologs regulate neuronal versus glial fate determination in the central nervous system."EMBO J.19:5460-5472. 19. 5460-5472 (2000)
[Publications] Kaneko,S.,Hikida,T.,Watanabe,D.,Ichinose,H.,Nagatsu,T.,Kreitman,R.J.,Pastan,I.and Nakanishi,S.: "Synaptic integration mediated by striatal cholinergic interneurons in basal ganglia function."Science. 289. 633-637 (2000)
[Publications] Tsuji,Y.,Shidama,Y.,Takeshita,T.,Kajimura,N.,Nomura,S.,Sekiyama,N.,Otomo,J.,Usukura,J.,Nakanishi,S.and Jingami,H.: "Cryptic dimer interface and domain organization of the extracellular region of metabotropic glutamate receptor subtype 1."J.Biol.Chem.. 275. 28144-28151 (2000)
[Publications] Kunishima,N.,Shimaka,Y.,Tsuji,Y.,Sato,T.,Yamamoto,M.,Kumasaka,T.,Nakanishi,S.,Jingami,H.and Morikawa,K.: "Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor."Nature 407 : 971-977.. 407. 971-977 (2000)
[Publications] Imamura,Y.,Inokawa,H.,Ito,A.,Kadotani,H.,Toyama,K.,Noda,M.,Nakanishi,S.and Hirano,T.: "Roles of GABAergic inhibition and NMDA receptor subunits in the spatio-temporal integration in the cerebellar cortex of mice."Neurosci.Res.. 38. 289-301 (2000)
[Publications] Kawasaki,H.,Mizuseki,K.,Nishikawa,S.,Kaneko,S.,Kuwana,Y.,Nakanishi,S.,Nishikawa,SI.and Sasai,Y.: "Induction of midbrain dopaminergic neurons from ES cells by stromal cell-drived inducing activity."Neuron 28:31-40. 28. 31-40 (2000)
[Publications] Yoshida,K.,Watanabe,D.,Ishikane,H.,Tachibana,M.,Pastan,I.and Nakanishi,S.: "A key role of starburst amacrine cells in originating retinal directional selectivity and optokinetic eye movement"Neuron. (in press). (2001)

2000 Fiscal Year Annual Research Report

獲得性生体情報の構築・応答ならびにその異常と病態の研究

Principal Investigator

本庶 佑 京都大学, 医学研究科, 教授 (80090504)

Research Products

[Publications] Latchman,Y.,(中略)Nishimura,H.,Honji,T.,Sharpe,A.and Freeman,G.: "PD-L2, a novel B7 homologue, is a second ligand for PD-1 and inhibits T cell activation."Nature Immunol.. (in press). (2001)

[Publications] Muramatsu,M.,and Honjo,T.: "Complex layers of genetic alteration in generation of antibody diversity."Immunol.Today. 22. 66-68 (2001)

[Publications] Nishimura,H.,Tanaka,Y.,Okazaki,T.,Nakatani,K.,Hara,M.,Matsumori,A.,Sasayama,S.,Hiai,H.,Minato,N.,and Honjo,T.: "Autoimmune dilated cardiomyopathy in PD-1 receptor deficient mice."Science. 291. 319-322 (2001)

[Publications] Tanigaki,K.,Nogaki,F.,Takahashi,J.,Tashiro,K.,Kurooka,H.,Honjo,T.: "Notch1 and Notch3 instructively restrict bFGF-responsive multipotent neural progenitor cells to an astroglial fate."Neuron. 29. 45-55 (2001)

[Publications] Watanabe,N.,Ikuta,K.,Fagarasan,S.,Yazumi,S.,Chiba,T.,and Honji,T.: "Migration and differentiation of autoreactive B-1 cells induced by activated γ/δ T cells in antierythrocyte immunoglobulin transgenic mice."J.Exp.Med.. 192. 1577-1586 (2000)

[Publications] Fagarasan,S.,and Honjo,T.: "T-independent immune response : New aspects of B cell biology."Science. 290. 89-92 (2000)

[Publications] Freeman,G.j.,Nishimura,H.,(中略) and Honjo,T.: "Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation."J.Exp.Med.. 192. 1027-1034 (2000)

[Publications] Revy,P.,(中略) Kinoshita,K.,Honjo,T.,Fischer,A.,and Durandy,A.: "Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the Hyper-IgM syndrome (HIGM2)."Cell. 102. 565-575 (2000)

[Publications] Muramatsu,M.,Kinoshita,K.,Fagarasan,S.,Yamada,S.,Shinkai,Y.,and Honjo,T.: "Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing eazyme."Cell. 102. 553-563 (2000)

[Publications] Muto,T.,Muramatsu,M.,Taniwaki,M.,Kinoshita,K.and Honjo,T.: "Isolation, tissue distribution and chromosomal localization of the human activation-induced cytidine deaminase (AID) gene."Genomics. 68. 85-88 (2000)

[Publications] Kurooka,H.and Honjo,T.: "Functional interaction between the mouse Notch1 intracellular region and histone acetyltransferases PCAF and GCN5."J.Biol.Chem.. 275. 17211-17220 (2000)

[Publications] Nishimura,H.,Honjo,T.,and Minato,N.: "Facilitation of b selection and modification of positive selection in the thymus of PD-1 deficient mice."J.Exp.Med.. 191. 891-897 (2000)

[Publications] Miyagawa,F.,Tanaka,Y.,Yamashita,S.and Minato,N.: "Essential requirement of antigen presentation by monocyte-lineage cells for the activation of primary human γδ T cells by aminobisphosphonate antigen."J.Immunol. in press. (2001)

[Publications] Nishimura,M.,Tanaka,Y.,Okazaki,T.,Nakatani,K.,Hara,M.,Nishio,R.,Matsumori,A.,Hiai,H.,Minato,N.and Honjo,T.: "Autoimmune dilated cardiomyopathy in PD-1 receptor deficient mice."Science. 291. 319-322 (2001)

[Publications] Suga,K.,Katagiri,K.,Harazaki,M.,Kinashi,T.,Hattori,M.and Minato,N.: "CD98 induces LFA-1-mediated cell adhesion in lymphoid cells via activation of."FEBS Letters.. 489. 249-253 (2001)

[Publications] Kageyama,T.,Nakamura,M.,Matsuo,A.,Yamasaki,Y.,Takakura,Y.,Hashida,M.,Kanai,Y.,Naito,M.,Tsuruo,T.,Minato,N.and Shimohama,S.: "The 4F2hc/LAT1 complex transports L-DOPA across the blood-brain barrier."Brain Res.. 879. 115-121 (2000)

[Publications] Katagiri,K.,Hattori,M.,Minato,N.,Irie,S.,Takatsu,K.,and Kinashi,T.: "Rap1 is a potent activation signal for LFA-1 distinct from PKC and PI3-kinase."Mol.Cell.Biol.. 20. 1956-1969 (2000)

[Publications] Kageyama,T.,Imura,T.,Yamazaki,Y.,Matsuo,A,Minato,N.and Shimohama,S.: "Disttribution of the 4F2 light chain, LAT1, in the mouse brain."Neuroreport. 11. 3663-3666 (2000)

[Publications] Nishimura,H.,Honjo,T.and Minato,N.: "Facillitation of β-selection and modification of positive selection in the thymus of PD-deficient mice."J.Exp.Med.. 191. 891-897

[Publications] Morimoto,M.,Kume,N.,Miyamoto,S.,Ueno,Y.,Kataoka,H.,Minami,M.,Hayashida,K.,Hashimoto,N.and Kita,T: "Lysophosphatidylcholine induces Egr-1 expression and activates the core promoter of PDGF-A chain in vascular endothelial cells."Arterioscler.Thromb.Vasc.Biol.. (in press). (2001)

[Publications] Kataoka,H.,Kume,N.,Miyamoto,S.,Minami,M.,Morimoto,M.,Hayashida,K.,Hashimoto,N.and Kita.T.: "Oxidized low density lipoprtoein (Ox-LDL) modulates Bax/Bcl-2 through lectin-like Ox-LDL receptor-1 in vascular smooth muscle cells."Arterioscler.Thromb.Vasc.Biol.. (in press). (2001)

[Publications] Ashida,N.,Arai,H.,Yamasaki,M.and Kita,T.: "Distinct signaling pathways for MCP-1-dependent integrin activation and chemotaxis."J.Biol.Chem.. (in press). (2001)

[Publications] Yamasaki,M.,Arai,H.,Ashida,N.,Ishii,K.and Kita,T.: "Monocyte chemoattractant protein-1 causes differential proline-rich tyrosin kinase 2-mediated signaling in THP-1 cells."Biochemical J.. (in press). (2001)

[Publications] Nakatani,J.,Mizuseki,K.,Tsuda,H.,Nakanishi,S.and Sasai,Y.: "Xenopus Xenf : An early endodermal nuclear factor that is regulated in a pathway distinct from Sox17 and Mix-related gene pathways."Mech.Dev.. 91. 81-89 (2000)

[Publications] Takao,M.,Morigiwa,K.,Sasaki,H.,Miyoshi,T.,Shima,T.,Nakanishi,S.,Nagai,K.and Fukuda,Y.: "Impaired behavioral Suppression by light in the mGluR6-deficient mice."Neuroscience. 97. 779-787 (2000)

[Publications] Kishi,M.,Mizuseki,K.,Sasai,N.,Yamazaki,H.,Shiota,K.Nakanishi,S.and Sasai,Y.: "Requirement of Sox2-mediated signaling for differentiation of early Xenopus neuroectoderm."Development. 127. 791-800 (2000)

[Publications] Matsui,M.,Mizuseki,K.,Nakatani,J.,Nakanishi,S.and Sasai,Y.: "Xenopus Kielin : A dorsalizing factor containing multiple chordin-type repeats secreted from the embryonic midline."Proc.Natl.Acad.Sci.USA. 97. 5291-5296 (2000)

[Publications] Tomita,K.,Moriyoshi,K.,Nakanishi,S.,Guillmot,F.and Kageyama,R.: "Mammalian achaete-scute and atonal homologs regulate neuronal versus glial fate determination in the central nervous system."EMBO J.19:5460-5472. 19. 5460-5472 (2000)

[Publications] Kaneko,S.,Hikida,T.,Watanabe,D.,Ichinose,H.,Nagatsu,T.,Kreitman,R.J.,Pastan,I.and Nakanishi,S.: "Synaptic integration mediated by striatal cholinergic interneurons in basal ganglia function."Science. 289. 633-637 (2000)

[Publications] Tsuji,Y.,Shidama,Y.,Takeshita,T.,Kajimura,N.,Nomura,S.,Sekiyama,N.,Otomo,J.,Usukura,J.,Nakanishi,S.and Jingami,H.: "Cryptic dimer interface and domain organization of the extracellular region of metabotropic glutamate receptor subtype 1."J.Biol.Chem.. 275. 28144-28151 (2000)

[Publications] Kunishima,N.,Shimaka,Y.,Tsuji,Y.,Sato,T.,Yamamoto,M.,Kumasaka,T.,Nakanishi,S.,Jingami,H.and Morikawa,K.: "Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor."Nature 407 : 971-977.. 407. 971-977 (2000)

[Publications] Imamura,Y.,Inokawa,H.,Ito,A.,Kadotani,H.,Toyama,K.,Noda,M.,Nakanishi,S.and Hirano,T.: "Roles of GABAergic inhibition and NMDA receptor subunits in the spatio-temporal integration in the cerebellar cortex of mice."Neurosci.Res.. 38. 289-301 (2000)

[Publications] Kawasaki,H.,Mizuseki,K.,Nishikawa,S.,Kaneko,S.,Kuwana,Y.,Nakanishi,S.,Nishikawa,SI.and Sasai,Y.: "Induction of midbrain dopaminergic neurons from ES cells by stromal cell-drived inducing activity."Neuron 28:31-40. 28. 31-40 (2000)

[Publications] Yoshida,K.,Watanabe,D.,Ishikane,H.,Tachibana,M.,Pastan,I.and Nakanishi,S.: "A key role of starburst amacrine cells in originating retinal directional selectivity and optokinetic eye movement"Neuron. (in press). (2001)

本庶佑京都大学, 医学研究科, 教授 (80090504)