Identification and dynamics of molecules involved in selective synapse formation

• Project/Area Number: 17024010
• 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
• Principal Investigator: NOSE Akinao The University of Tokyo, 大学院・新領域創成科学研究科, 教授 (30260037)
• Co-Investigator(Kenkyū-buntansha): MORIMOTO Takako 東京薬科大学, 生命科学部, 准教授 (10311648) ; TAKASU Etsuko 東京大学, 大学院・理学系研究科, 助教 (30282718) ; KOHSAKA Hiroshi 東京大学, 大学院・理学系研究科, 助教 (20431900)
• Research Collaborator: INAKI Mikiko 東京大学, 大学院・理学系研究科, 研究員
• Project Period (FY): 2005 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥85,900,000 (Direct Cost: ¥85,900,000); Fiscal Year 2009: ¥18,000,000 (Direct Cost: ¥18,000,000); Fiscal Year 2008: ¥16,900,000 (Direct Cost: ¥16,900,000); Fiscal Year 2007: ¥16,500,000 (Direct Cost: ¥16,500,000); Fiscal Year 2006: ¥17,400,000 (Direct Cost: ¥17,400,000); Fiscal Year 2005: ¥17,100,000 (Direct Cost: ¥17,100,000)
• Keywords: シナプス / 神経回路 / イメージング / マイクロアレイ / ショウジョウバエ / 標的認識 / 軸索誘導 / シナプス形成 / 神経標的認識機構 / 神経筋結合 / Toll / Tey / LRR(leucine-rich repeat) / 運動神経 / 筋肉 / Wnt / 標的認識分子 / 細胞接着分子 / 神経回路形成 / ファシクリン / ジーンチップ

Research Abstract

Synapses are specialized junctions through which neurons signal to each other and to other target cells such as muscles and are crucial to the functioning of the nervous system. Neurons select and synapse with specific target cells. This "synaptic specificity" underlies the proper functioning of the nervous system. In this study, we used highly sophisticated Drosophila genetics to reveal a novel mechanism by which neurons find and recognize their target cells. We also succeeded in visualizing the process of synapse formation in developing embryos and elucidated a molecular mechanism of synapse formation that occurs in an intact organism.

Research Products

• [Journal Article] Drosophila Tey represses transcription of a repulsive cue Toll and generates neuromuscular target specificity. (2010)
  • Author(s): Inaki M, Shinza-Kameda M, Ismat A, Frasch M, Nose A
  • Journal Title: Development 137 Pages: 2139-2146
  • Peer Reviewed
• [Journal Article] Subunit-specific and homeostatic regulation of glutamate receptor localization by CaMKII in Drosophila neuromuscular junctions. (2010)
  • Author(s): Morimoto T, Nobechi M, Komatsu A, Miyakawa H, Nose A
  • Journal Title: Neuroscience 165 Pages: 1284-1292
  • Peer Reviewed
• [Journal Article] Drosophila Tey represses transcription of a repulsive cue Toll and generates neuromuscular target specificity. (2010)
  • Author(s): Inaki, M., Shinza-Kameda, M., Ismat, A., Frasch., M., Nose, A.
  • Journal Title: Development Volume: 137 Pages: 2139-2146
  • Peer Reviewed
• [Journal Article] Target recognition at the tips of postsynaptic filopodia : accumulation and function of Capricious. (2009)
  • Author(s): Kohsaka H, Nose A
  • Journal Title: Development 136 Pages: 1127-1135
  • Peer Reviewed
• [Journal Article] Molecular mechanisms underlying neural circuit formation. (2009)
  • Author(s): Lu B, Wang KH, Nose A
  • Journal Title: Current opinion in neurobiology 19 Pages: 162-167
• [Journal Article] Innervation and activity dependent dynamics of postsynaptic oxidative metabolism. (2008)
  • Author(s): Kazama H, Ichikawa A, Kohsaka H, Morimoto-Tanifuji T, Nose A
  • Journal Title: Neuroscience 152 Pages: 40-49
  • Peer Reviewed
• [Journal Article] Innervation and activity dependent dynamics of postsynaptic oxidative metabolism. (2008)
  • Author(s): 風間北斗、市川彩子、高坂洋史、森本(谷藤)高子、能瀬聡直
  • Journal Title: Neuroscience 152 Pages: 40-49
  • Peer Reviewed
• [Journal Article] In vivo induction of postsynaptic molecular assembly by the cell adhesion molecule Fasciclin2. (2007)
  • Author(s): Kohsaka H, Takasu E, Nose A
  • Journal Title: The Journal of cell biology 179 Pages: 1289-1300
  • Peer Reviewed
• [Journal Article] Wnt4 is a local repulsive cue that determines synaptic target specificity. (2007)
  • Author(s): Inaki M, Yoshikawa S, Thomas JB, Aburatani H, Nose A
  • Journal Title: Current biology : CB 17 Pages: 1574-1579
  • Peer Reviewed
• [Journal Article] Synaptic components necessary for retrograde signaling triggered by calcium/calmodulin-dependent protein kinase II during synaptogenesis. (2007)
  • Author(s): Kazama H, Nose A, Morimoto-Tanifuji T
  • Journal Title: Neuroscience 145 Pages: 1007-1015
  • Peer Reviewed
• [Journal Article] 神経特異結合の分子機構-負のシグナルによる標的決定 (2007)
  • Author(s): 能瀬聡直, 稲木美紀子, 新座(亀田)麻記子
  • Journal Title: 蛋白質・核酸・酵素 53 Pages: 531-536
• [Journal Article] Wnt4 is a local repulsive cue that determines synaptic target specificity. (2007)
  • Author(s): 稲木美紀子、Yoshikawa, S., Thomas, J.B., 油谷浩幸, 能瀬聡直
  • Journal Title: Current Biology 17 Pages: 1574-1579
  • Peer Reviewed
• [Journal Article] In vivo induction of postsynaptic molecular assembly by the cell adhesion molecule Fasciclin2. (2007)
  • Author(s): 高坂洋史、高須悦子、能瀬聡直
  • Journal Title: Journal of Cell Biology 179 Pages: 1289-1300
  • Peer Reviewed
• [Journal Article] Synaptic components necessary for retrograde signaling triggered by calcium/calmodulin-dependent prntein kinase II during synaptogenesis. (2007)
  • Author(s): 風間北斗、能瀬聡直、森本(谷藤)高子
  • Journal Title: Neuroscience 145 Pages: 1007-15
• [Journal Article] Activity-dependent regulation of synaptic size in Drosophila neuromuscular junctions. (2006)
  • Author(s): Nakayama H, Kazama H, Nose A, Morimoto-Tanifuji T
  • Journal Title: Journal of neurobiology 66 Pages: 929-939
  • Peer Reviewed
• [Journal Article] Regulation of ayer-specific targeting by reciprocal expression of a cell adhesion molecule (2006)
  • Author(s): Shinza-Kameda M, Takasu E, Sakurai K, Hayashi S, Nose A
  • Journal Title: capricious.Neuron 49 Pages: 205-213
  • Peer Reviewed
• [Journal Article] 神経・筋シナプス形成機構の新展開 (2006)
  • Author(s): 能瀬聡直
  • Journal Title: 臨床麻酔 30 Pages: 1811-1818
• [Journal Article] Activity-dependent regulation of synaptic size in Drosophila neuromuscular junctions. (2006)
  • Author(s): 中山浩明、風間北斗、能瀬聡直、森本(谷藤)高子
  • Journal Title: Journal of Neurobiology 66 Pages: 929-939
• [Journal Article] Regulation of layer-specific targeting by reciprocal expression of a cell adhesion molecule, capricious (2006)
  • Author(s): Shinza-Kameda, M., Takasu, E., Sakurai, K., Hayashi, S., Nose, A.
  • Journal Title: Neuron 49 Pages: 205-213
• [Journal Article] Activity-dependent regulation of synaptic size in Drosophila neuromuscular junctions. (2006)
  • Author(s): Nakayama, H., Kazama, H., Nose, A., Morimoto-Tanifuji, T.
  • Journal Title: Journal of Neurobiology (印刷中)
• [Journal Article] 神経筋連絡の特異性を制御する分子機構 (2005)
  • Author(s): 能瀬聡直, 高坂洋史
  • Journal Title: 神経科学の進歩 49 Pages: 85-93
• [Presentation] Generation of synaptic specificity by target repulsion Roles and transcriptional regulation of local inhibitory cues. (2010)
  • Author(s): Inaki, M., Shinza-Kameda, M., Frasch, M., Nose A.
  • Organizer: Cold Spring Harbor Asia Francis Crick Symposium on Neuroscience
  • Place of Presentation: Suzhou, China
• [Presentation] Generation of synaptic specificity by target repulsion-Roles and transcriptional regulation of local inhibitory cues. (2010)
  • Author(s): Inaki, M., Shinza-Kameda, M., Frasch, M., Nose, A.
  • Organizer: Cold Spring Harbor Asia Francis Crick Symposium on Neuroscience
  • Place of Presentation: Suzhou,中国
• [Presentation] Generation of synaptic specificity by target repulsion : Roles and transcriptional regulation of local inhibitory cues. (2009)
  • Author(s): Nose A.
  • Organizer: Constructing Neural Circuits meeting at Janelia Farm
  • Place of Presentation: USA.
• [Presentation] Formation and plasticity of neural circuits regulating peristaltic movements of Drosophila larvae (2009)
  • Author(s): Kohsaka, H., Tachi, Y., Nose A.
  • Organizer: Constructing Neural Circuits meeting at Janelia Farm.
  • Place of Presentation: USA.
• [Presentation] Generation of synaptic specificity by target repulsion : Roles and transcriptional regulation of local inhibitory cues. (2009)
  • Author(s): Nose, A.
  • Organizer: "Constructing Neural Circuits" meeting at Janelia Farm.
  • Place of Presentation: Ashburn,米国
• [Presentation] Generation of synaptic specificity by repulsion (2008)
  • Author(s): Nose A.,Inaki, M., Shinza-Kameda, M.
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会シンポジウム
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-10
• [Presentation] Dynamisms of postsynaptic filopodia during target recognition of Drosophila Neuromuscular Junction NeuroFly2008 (2008)
  • Author(s): Kohsaka, H., Nose A.
  • Organizer: 12th European Drosophila neurobiology conference
  • Place of Presentation: Wurzburg, Germany
• [Presentation] Dynamisms of postsynaptic filopodia during target recognition of Drosophila Neuromuscular Junction. (2008)
  • Author(s): Kohsaka, H., Nose A.
  • Organizer: 第31回日本神経科学大会
  • Place of Presentation: 東京
• [Presentation] Induction of molecular assembly by cell adhesion molecule in Drosophila neuromuscular junction (2008)
  • Author(s): Hiroshi Kohsaka, Etsuko Takasu, Akinao Nose
  • Organizer: US-Japan Brain Research Collaborative Program "Workshop on Receptor Trafficking and Cell Biology of Neurons : Physiology and Disease"
  • Place of Presentation: Asilomar, USA
• [Presentation] Imaging postsynaptic assembly of the cell adhesion molecule Fasciclin2 in neuromuscular synaptogenesis. (2007)
  • Author(s): Kohsaka, H., Takasu, E., Nose, A.
  • Organizer: Cold Spring Harbor Meeting on "Neurobiology of Drosophila"
  • Place of Presentation: Cold Spring Harbor
• [Presentation] Wnt4 is a local repulsive cue that determines target specificity. (2007)
  • Author(s): Nose, A., Inaki, M, Aburatani, H.
  • Organizer: 第30回日本神経科学大会
  • Place of Presentation: 横浜
• [Presentation] Postsynaptic accumulation of cell adhesion molecules imaged in vivo. (2007)
  • Author(s): Kohsaka, H., Takasu, E., Nose, A.
  • Organizer: 第30回日本神経科学大会
  • Place of Presentation: 横浜
• [Presentation] 神経標的決定の制御機構 : Wnt4を介した負の選択 (2007)
  • Author(s): 能瀬聡直
  • Organizer: 日本分子生物学会年会・日本生化学会大会 合同大会2007
  • Place of Presentation: 横浜
• [Presentation] Dynamism and regulation of synaptic assembly at the neuromuscular junction in Drosophila. (2006)
  • Author(s): Kohsaka, H., Takasu, E., Nose, A.
  • Organizer: 5th East Asian Biophysics Symposium & 44th annual meeting of the Biophysical Society of Japan.
  • Place of Presentation: Okinawa.
• [Presentation] Expression profiling of synaptic specificity : target selection by Wnt4-mediated repulsion. (2006)
  • Author(s): Inaki, M., Aburatani H., Nose A.
  • Organizer: 36th Annual Meeting of the Society for Neuroscience
  • Place of Presentation: Atlanta.
• [Presentation] Distinct localization of cell adhesion molecules for the target recognition and synapse formation in early phase of synaptogenesis in vivo. (2006)
  • Author(s): Kohsaka, H., Takasu E., Nose, A.
  • Organizer: Cold Spring Harbor Meeting on "Axon Guidance, Synaptogenesis & Neural Plasticity"
  • Place of Presentation: Cold Spring Harbor.
• [Presentation] Single-cell microarray identified Wnt4 as a local repulsive cue that determines target specificity. (2006)
  • Author(s): Inaki, M., Aburatani H., Nose A.
  • Organizer: Cold Spring Harbor Meeting on "Axon Guidance, Synaptogenesis & Neural Plasticity"
  • Place of Presentation: Cold Spring Harbor
• [Presentation] Genome-wide search for the neuromuscular target recognition molecules in Drosophila using single cell expression analysis. (2006)
  • Author(s): 稲木美紀子, 鈴木良枝, 油谷浩幸, 能瀬聡直
  • Organizer: 第29回日本神経科学大会
  • Place of Presentation: 京都
• [Presentation] Initial molecular steps in synaptogenesis in vivo : trans-synaptic interaction of cell adhesion molecule is involved in postsynaptic assembly of PSD95-homolog Dlg. (2006)
  • Author(s): 高坂洋史、高須悦子、能瀬聡直
  • Organizer: 第29回日本神経科学大会
  • Place of Presentation: 京都
• [Presentation] Recognition by postsynaptic filopodia and dynamics of molecular assembly during early phase of synaptogenesis. (2005)
  • Author(s): Hiroshi Kohsaka, Etsuko Takasu, Akinao Nose
  • Organizer: 2005 meeting on "Neurobiology of Drosophila"
  • Place of Presentation: Cold Spring Harbor, USA
• [Remarks] 日経産業新聞(2006年1月19日)脳神経結合の目印発見
  • URL: http://bio.phys.s.u-tokyo.ac.jp/
• [Remarks] 毎日新聞(2006年1月22日)神経の誘導物質発見
• [Remarks] 朝日新聞(2006年1月24日夕刊)正しくつながる神経細胞の目印
• [Remarks] 科学新聞(2006年1月27日4面)神経細胞の正確な配線機構解明
• [Remarks] 読売新聞(2006年2月1日)脳神経結合の目印特定日経産業新聞(2007年8月31日10面)神経との接続を拒むたんぱく質を発見
• [Remarks] 日刊工業新聞(2007年8月31日27面)負の印から正しい配線
• [Remarks] 読売新聞(2007年9月2日朝刊2面)誤った神経結合拒むたんぱく質
• [Remarks] 毎日新聞(2007年9月5日朝刊15面)神経誘導物質を発見
• [Remarks] 科学新聞(2007年9月21日2面)神経回路形成で働く負の目印
• [Remarks] 日刊工業新聞(2007年12月18日22面)動物個体のシナプス形成過程を可視化
• [Remarks] 科学新聞(2008年1月1日4面)シナプス構築の仕組み明らかに
• [Remarks] 東京読売新聞朝刊(2008年1月6日19面)神経と筋肉「接続」の瞬間
• [Remarks] 日経産業新聞(2008年1月7日9面)シナプスの形成過程生体内で可視化
• [Remarks] 東京新聞朝刊(2008年1月15日15面)シナプス形成生体内で観察
• [Remarks] 中日新聞夕刊(2008年1月15日10面)シナプス形成生体内で観察
• [Remarks] 毎日新聞朝刊(2008年2月17日19面)シナプス形成過程ハエの卵で初確認
• [Remarks] 日経産業新聞(2009年3月9日11面)神経つなぐ仕組み双方の細胞で認識
• [Remarks] 科学新聞(2009年3月13日7面)神経回路を正しく接続するための双方向探索機構を解明
• [Remarks] 日刊工業新聞Newウェーブ21(2009年3月24日31面)神経回路形成は双方向
• [Remarks] 日本経済新聞(2011年3月20日)ミクロで観る生命4.成長するハエの卵、神経回路ができる瞬間
• [Remarks] ホームページ
• [Remarks]
  • URL: http://bio.phys.s.u-tokyo.ac.jp/