Mechanisms of axon collateral formation by cell-intrinsic Dscam1-Dscam1 interactions

• Project/Area Number: 16K18536
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cell biology
• Research Institution: The University of Tokyo
• Principal Investigator: Kise Yoshiaki 東京大学, 大学院理学系研究科(理学部), 特任助教 (70769611)
• Research Collaborator: Dietmar Schmucker
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 軸索分枝 / 軸索 / 分枝 / シグナル伝達

Outline of Final Research Achievements

This project aims to reveal molecular mechanisms of axon collateral formation controlled by cell-intrinsic Dscam-Dscam interactions. We have identified two cytoskeleton regulators which interact with Dscam biochemically. Loss-of-function and gain-of-function analysis have shown that these two molecules are required for axon collateral formation. Furthermore, epistasis and genetic analysis indicate that Dscam and these two molecules are in the same signaling pathway required for axon collateral formation.

Academic Significance and Societal Importance of the Research Achievements

軸索側枝形成には、既存の主軸索の特定の地点から軸索が新たに形成され、それぞれが異なる目的地へ投射される必要がある。申請者らは、（１）Dscamが軸索側枝形成のマスター因子であること、（２）Dscamシグナルの時空間制御が軸索側枝形成に必要であることをこれまでに見出してきた。本研究では、これまで不明だったDscamシグナルの分子機構を明らかにすることができた。本成果は、軸索側枝形成の分子機構の解明に大きく貢献するばかりでなく、損傷を負った軸索に対してDscamシグナルを時空間操作することによって軸索側枝の形成を誘導し、軸索を再生させることができる可能性を提示することができた。

Research Products

• [Int'l Joint Research] VIB, University of Leuven(ベルギー)
• [Int'l Joint Research] Iowa State University(米国)
• [Int'l Joint Research] University of Leuven(Belgium)
• [Int'l Joint Research] University of Leuven(Belgium)
• [Journal Article] Nuclear import of the DSCAM-cytoplasmic domain drives signaling capable of inhibiting synapse formation. (2019)
  • Author(s): Sachse SM, Lievens S, Ribeiro LF, Dascenco D, Masschaele D, Horre K, Misbaer A, Vanderroost N, De Smet AS, Salta E, Erfurth ML, Kise Y, Nebel S, Van Delm W, Plaisance S, Tavernier J, De Strooper B, De Wit J, Schmucker D.
  • Journal Title: EMBO J Volume: 38 Issue: 6
  • DOI: 10.15252/embj.201899669
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Molecular signaling pathways regulating axon branching via Dscam1 (2018)
  • Author(s): Kise Y, Izadifar A, Schmucker D, Emoto K
  • Organizer: The 41st Annual Meeting of the Japan Neuroscience Society in 2018 at Kobe
• [Presentation] Studying diversity and functions of clustered protocadherins in Xenopus tropicalis (2016)
  • Author(s): Zengjin Huang, Yoshiaki Kise, Changsheng Chen, Sun Wei, Emre Etlioglu, Maximilian Ulbrich, Wei Chen, Dietmar Schmucker
  • Organizer: Cold Spring Harbor Laboratory Meeting on Axon guidance, Synapse formation & Regeneration
  • Place of Presentation: Cold Spring Harbor (the USA)
  • Year and Date: 2016-09-20
  • Int'l Joint Research