Analysis of molecular mechanisms establishing the circuit connectivity in the cerebellar afferent fibers

• Project/Area Number: 25430073
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Keio University
• Principal Investigator: KUWAKO KEN-ICHIRO 慶應義塾大学, 医学部, 特任講師 (30468475)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 神経回路 / シナプス結合 / 軸索伸展 / 遺伝子発現 / 神経回路形成 / シナプス / 軸索 / 小脳

Outline of Final Research Achievements

We identified cadherin-7 (Cdh7) as a critical regulator of synaptic specificity in the cerebellar mossy fiber circuit between pontine nucleus neurons and cerebellar granule neurons. Cdh7 plays a dual role in target recognition and axonal growth termination to establish the specific synaptic connections in the cerebellar mossy fiber circuit. Several cadherin family members including Cdh7 are expressed in the cerebellar afferent fiber circuits (i.e. mossy fiber and climbing fiber) in a circuit-specific manner and the precise control of their expression is essential to the circuit connectivity. Through combinatorial analysis, some potential candidate regulators for the expression of those cadherins were identified.

Research Products

• [Journal Article] Cadherin-7 regulates the circuit connectivity of the cerebellar mossy fiber. (2014)
  • Author(s): Kuwako K, Nishimoto Y, Kawase S, Okano HJ, Okano H.
  • Journal Title: Cell Rep. Volume: 9 Issue: 1 Pages: 331-323
  • DOI: 10.1016/j.celrep.2014.08.063
  • Peer Reviewed / Open Access
• [Journal Article] Rfx Transcription Factors Control Musashi1 Transcription in Mouse Neural Stem/Progenitor Cells. (2014)
  • Author(s): Kawase S, Kuwako K, Imai T, Renault-Mihara F, Yaguchi K, Itohara S, Okano H.
  • Journal Title: Stem Cells Dev. Volume: 23 Issue: 18 Pages: 2250-2261
  • DOI: 10.1089/scd.2014.0219
  • Peer Reviewed
• [Journal Article] The long non-coding RNA nuclear-enriched abundant transcript 1_2 induces paraspeckle formation in the motor neuron during the early phase of amyotrophic lateral sclerosis (2013)
  • Author(s): Nishimoto, Y., Nakagawa, S., Hirose, T., Okano, H. J., Takao, M., Shibata, S., Suyama, S., Kuwako, K., Imai, T., Murayama, S., Suzuki, N., and Okano, H
  • Journal Title: Mol. Brain Volume: 6 Issue: 1 Pages: 31-31
  • DOI: 10.1186/1756-6606-6-31
  • Peer Reviewed
• [Presentation] Cadherin蛋白質による特異的回路接続 (2016)
  • Author(s): 桑子賢一郎
  • Organizer: 第１２１回日本解剖学会 シンポジウム：２１世紀の発生神経科学を解剖する ―今後の回路発達研究の新展開をめざして―
  • Place of Presentation: ビッグパレットふくしま（福島県郡山市）
  • Year and Date: 2016-03-28
  • Invited
• [Presentation] Mechanism for regulating the connectivity of cerebellar afferent fibers (2016)
  • Author(s): 桑子賢一郎、岡野栄之
  • Organizer: 第９回神経発生討論会
  • Place of Presentation: 東京医科歯科大学（東京都文京区）
  • Year and Date: 2016-03-19
• [Presentation] Cadherin-7 regulates the circuit connectivity of the cerebellar mossy fiber (2014)
  • Author(s): 桑子賢一郎、岡野栄之
  • Organizer: 第３７回日本神経科学会
  • Place of Presentation: パシフィコ横浜（ 神奈川県）
  • Year and Date: 2014-09-12
• [Presentation] 小脳辺縁系神経回路のシナプス接続を制御する分子機構の解析 (2013)
  • Author(s): 桑子賢一郎、岡野栄之
  • Organizer: 第３５回日本神経科学会
  • Place of Presentation: 国立京都国際会館