Axon branch remodeling mechanisms in mesoscopic neuronal circuit formation

• Project Area: Mesoscopic neurocircuitry: towards understanding of the functional and structural basis of brain information processing
• Project/Area Number: 23115102
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Osaka University
• Principal Investigator: YAMAMOTO Nobuhiko 大阪大学, 生命機能研究科, 教授 (00191429)
• Co-Investigator(Kenkyū-buntansha): 藤島 和人 京都大学, 物質－細胞統合システム拠点, 特定拠点助教 (20525852)
• Co-Investigator(Renkei-kenkyūsha): SUGO Noriyuki 大阪大学, 大学院生命機能研究科, 助教 (20372625)
• Project Period (FY): 2011-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥49,660,000 (Direct Cost: ¥38,200,000、Indirect Cost: ¥11,460,000); Fiscal Year 2014: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000); Fiscal Year 2013: ¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000); Fiscal Year 2012: ¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000)
• Keywords: 軸索分岐 / 大脳 / 視床 / 神経活動 / RhoA / Unc5B / netrin-4 / 樹状突起 / 視床由来分子 / 軸索誘導 / ネトリン / 受容体

Outline of Final Research Achievements

The aim of this study is to reveal the role of neuronal activity in axon branching and the molecular mechanisms of branch formation, focusing on the thalamocortical projection system. We found that branching of thalamocortical axons is promoted by target-derived molecules which are expressed in an activity-dependent fashion and that an activity-independent mechanism also works on axon branching. We furhter found that branches mostly emerge from presynaptic sites of thalamic axons in normal conditions but appear from non-presynaptic sites with high neuronal activity. Evidence also suggests that a cytoskeleton-regulatory mechanism is involved in axon branching.

Research Products

• [Journal Article] Synapse-dependent and independent mechanisms of thalamocortical axon branching are regulated by neuronal activity (2016)
  • Author(s): Matsumoto, N., Hoshiko, M., Sugo, N., Fukazawa, Y. & Yamamoto, N.
  • Journal Title: Developmental Neurobiology Volume: 76 Issue: 3 Pages: 323-336
  • DOI: 10.1002/dneu.22317
  • Peer Reviewed
• [Journal Article] Single-molecule imaging reveals dynamics of CREB transcription factor bound to its target sequence (2015)
  • Author(s): Sugo, N., Morimatsu, M., Arai, Y., Kousoku, Y., Ohkuni, A., Nomura, T., Yanagida, T. & Yamamoto, N.
  • Journal Title: Scientific Report Volume: 5 Issue: 1 Pages: 10662-10662
  • DOI: 10.1038/srep10662
  • Peer Reviewed / Open Access
• [Journal Article] Adaptive phenotype of microglial cells during the normal postnatal development of the somatosensory "barrel" cortex (2013)
  • Author(s): Arnoux I, Hoshiko M, Mandavy L, Avignone E, Yamamoto N, Audinat E
  • Journal Title: Glia Volume: 61 Pages: 1582-1594
  • Peer Reviewed
• [Journal Article] Role of electrical activity in horizontal axon growth in the developing cortex: A time-lapse Study using optogenetic Stimulation (2013)
  • Author(s): Malyshevskaya O, Shiraishi Y, Kimura F, Yamamoto N
  • Journal Title: PLOS ONE Volume: 8
  • Peer Reviewed
• [Journal Article] Regulation of thalamocortical axon branching by BDNF and synaptic vesicle cycling (2013)
  • Author(s): Granseth B, Fukushima Y, Sugo N, Lagnado L, Yamamoto N
  • Journal Title: Front Neural Circuits Volume: 7 Pages: 202-202
  • Peer Reviewed
• [Journal Article] Deficiency of the microglial receptor CX3CR1 impairs postnatal functional development of thalamocortical synapses in the barrel cortex (2012)
  • Author(s): Hoshiko, Maki
  • Journal Title: The Journal of Neuroscience Volume: 32 Pages: 15106-15111
  • Peer Reviewed
• [Journal Article] Thalamus-derived molecules promote survival and dendritic growth of developing cortical neurons (2012)
  • Author(s): Sato, Haruka
  • Journal Title: The Journal of Neuroscience Volume: 32 Pages: 15388-15402
  • Peer Reviewed
• [Journal Article] Shaping Brain connections through spontaenous neural activity (2012)
  • Author(s): Yamamoto, Nobuhiko
  • Journal Title: European Journal of Neuroscience Volume: 35 Pages: 1595-1604
  • Peer Reviewed
• [Journal Article] Principles of branch dynamics governing shape characteristics of cerebellar Purkinje cell dendrites (2012)
  • Author(s): Fujishima, Kazuto
  • Journal Title: Development Volume: 139 Pages: 3442-3455
  • Peer Reviewed
• [Journal Article] Laminar and Areal Expression of Unc5d and Its Role in Cortical Cell Survival (2011)
  • Author(s): Takemoto, et al
  • Journal Title: Cerebral Cortex Volume: 21 Pages: 925-34
  • Peer Reviewed
• [Journal Article] The action of Semaphorin7A on thalamocortical axon branching (2011)
  • Author(s): Fukunishi, et al
  • Journal Title: Journal of Neurochemistry Volume: 118 Pages: 1008-15
  • Peer Reviewed
• [Journal Article] A molecular mechanism that regulates medially oriented axonal growth of upper layer neurons in the developing neocortex (2011)
  • Author(s): Zhao, et al
  • Journal Title: Journal of Comparative Neurology Volume: 519 Pages: 925-34
  • Peer Reviewed
• [Presentation] Polβ deficiency increases DNA double-strand breaks in postnatal cortical (2015)
  • Author(s): Uyeda, A., Onishi, K., Sugo, N., Toyoda S., Hiyayama, T., Yagi, T. & Yamamoto, N.
  • Organizer: 第38回日本分子生物学会
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-01
• [Presentation] DNA polymerase β activity in neural progenitors is required for postmitotic neuronal survival in the developing cortex (2015)
  • Author(s): Onishi, k., Sugo, N., Toyoda, S., Hirayama, T., Yagi, T. & Yamamoto, N.
  • Organizer: Society for Neuroscience
  • Place of Presentation: Chicago, USA
  • Year and Date: 2015-10-17
  • Int'l Joint Research
• [Presentation] Activity-dependent dynamics of CREB in cortical neurons: A single-molecule imaging study (2015)
  • Author(s): Kitagawa, H., Sugo., N. & Yamamoto, N.
  • Organizer: Society for Neuroscience
  • Place of Presentation: Chicago, USA
  • Year and Date: 2015-10-17
  • Int'l Joint Research
• [Presentation] Involvement of mitochondria in thalamocortical axon branching (2015)
  • Author(s): Matsumoto, N., Hoshiko, M. & Yamamoto, N.
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 横浜
  • Year and Date: 2015-07-28
• [Presentation] Rho guanine nucleotide exchange factor Abr promotes axon branching in cortical layer 2/3 neurons (2015)
  • Author(s): Sasaki, K., Arimoto, K., Kankawa, K., Terada, C. & Yamamoto,
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 横浜
  • Year and Date: 2015-07-28
• [Presentation] 神経活動依存的な軸索分岐のリモデリング (2013)
  • Author(s): 山本亘彦
  • Organizer: 日本生理学会大会
  • Place of Presentation: 東京
  • Year and Date: 2013-03-27
  • Invited
• [Presentation] 神経活動依存的な皮質神経回路の分子機構 (2013)
  • Author(s): 山本 亘彦
  • Organizer: 第86回日本生化学大会
  • Place of Presentation: 横浜
  • Invited
• [Presentation] 1分子イメージングによる転写因子CREBの動態解析 (2012)
  • Author(s): 菅生 紀之
  • Organizer: 第35回日本分子生物学会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-11
• [Presentation] 神経活動依存的な軸索分岐の制御機構 (2012)
  • Author(s): 山本 亘彦
  • Organizer: 神経組織の成長・再生・移植研究会第27回学術集会
  • Place of Presentation: 東京
  • Year and Date: 2012-10-26
  • Invited
• [Presentation] Activity-dependent expression of Netrin-4 regulates thalamocortical axon branching, (2012)
  • Author(s): Hayano, Yasufumi
  • Organizer: Society for Neuroscience 42nd annual meeting
  • Place of Presentation: New Orleans, The U.S.A.
  • Year and Date: 2012-10-13
• [Presentation] Single-molecule imaging of transcription factor CREB in living cells, Society for Neuroscience 42nd annual meeting (2012)
  • Author(s): Sugo, Noriyuki
  • Organizer: Society for Neuroscience 42nd annual meeting
  • Place of Presentation: New Orleans, The U.S.A.
  • Year and Date: 2012-10-13
• [Presentation] The role of neuronal activity in cortical axon growth: A time-lapse study using optogenetic control (2012)
  • Author(s): Malyshevskaya, Olga
  • Organizer: Society for Neuroscience 42nd annual meeting
  • Place of Presentation: New Orleans, The U.S.A.
  • Year and Date: 2012-10-13
• [Presentation] Molecular mechanisms of thalamocortical axon branching: Nature and Nurture programs (2012)
  • Author(s): Yamamoto, Nobuhiko
  • Organizer: The 35th Annual Meeting of the Japan Neuroscience society
  • Place of Presentation: Nagoya
  • Year and Date: 2012-09-18
  • Invited
• [Presentation] 1分子イメージングによる転写因子CREBの核内動態解析 (2012)
  • Author(s): 菅生 紀之
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋
  • Year and Date: 2012-09-18
• [Presentation] 視床皮質軸索の枝分かれ形成に対するシナプス形成の役割 (2012)
  • Author(s): 松本 直之
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋
  • Year and Date: 2012-09-18
• [Presentation] マウス大脳皮質における入力線維依存的な領野特異的細胞構築 (2012)
  • Author(s): 佐藤-竹本 晴香
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋
  • Year and Date: 2012-09-18
• [Presentation] Activity-dependent mechanisms of cortical circuit formation
  • Author(s): Yamamoto N
  • Organizer: Neuro2013 Formal Satellite Symposium
  • Place of Presentation: Kyoto
  • Invited
• [Presentation] 大脳皮質における神経活動依存的・非依存的な神経回路形成の制御機構 - 氏か育ちか
  • Author(s): 山本 亘彦
  • Organizer: 第35回神経組織培養研究会
  • Place of Presentation: 大阪
  • Invited
• [Presentation] Molecular Mechanisms of Activity-Dependent Cortical Circuit Formation
  • Author(s): Yamamoto N
  • Organizer: Special Neurobiology Seminar in Yale University
  • Place of Presentation: New Haven
  • Invited
• [Book] 脳の発生学 (2013)
  • Author(s): 宮田卓樹・山本亘彦
  • Total Pages: 263
  • Publisher: 化学同人
• [Remarks] 大阪大学大学院生命機能研究科 細胞分子神経生物学研究室 （山本亘彦研究室）
  • URL: http://www.fbs.osaka-u.ac.jp/labs/neurobiol/
• [Remarks] 細胞分子神経生物学研究室 （山本亘彦研究室）
  • URL: http://www.fbs.osaka-u.ac.jp/labs/neurobiol/
• [Remarks] 細胞分子神経生物学研究室 （山本亘彦研究室） 大阪大学大学院生命機能研究科
  • URL: http://www.fbs.osaka-u.ac.jp/labs/neurobiol/
• [Remarks]
  • URL: http://www.fbs.osaka-u.ac.jp/labs/neurobiol/