A Study on function of protocadherin 1 cell adhesion molecule in the nervous system.

• Project/Area Number: 18K06230
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 44010:Cell biology-related
• Research Institution: Kansai Medical University
• Principal Investigator: HIRANIO Shinji 関西医科大学, 医学部, 教授 (80222248)
• Co-Investigator(Kenkyū-buntansha): 古瀬 民生 国立研究開発法人理化学研究所, バイオリソース研究センター, 開発研究員 (60392106)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 細胞接着分子 / プロトカドヘリン / カドヘリン / 情動 / 扁桃体 / 不安 / 行動解析 / 神経回路 / シナプス / 細胞接着 / 自閉症 / 社会性行動

Outline of Final Research Achievements

We analyzed various cadherin molecules. Regarding protocadherin 1(Pcdh1), we examined the expression pattern and behavior in the knock-out mice. Regarding Pcdh9, we observed a reduction of spine density and abnormal behaviors, and its expression in the fear-related neurons in the amygdala, suggesting the possibility that Pcdh9 is involved in the formation of fear and emotion via the amygdala and hippocampus. In addition, we analyzed the relationship between matrix molecules and classic cadherins.

Academic Significance and Societal Importance of the Research Achievements

本研究は研究が遅れているプロトカドヘリン分子群の機能と役割を明らかにしようとするものであり、Pcdh1およびPcdh9の発現解析とそれらのノックアウトマウスの解析から、これらの分子の基本的な発現部位、および行動異常を明らかにした。その結果はそれらの機能と役割を細胞レベルで示唆するものであり、細胞接着分子や神経回路形成の基礎研究分野に貢献するものである。さらに。プロトカドヘリン分子群は精神疾患の関連遺伝子として知られており、本研究による結果が精神疾患の発症メカニズムの理解につながることが期待される。

Research Products

• [Journal Article] Specific substrates composed of collagen and fibronectin support the formation of epithelial cell sheets by MDCK cells lacking α-;catenin or classical cadherins (2021)
  • Author(s): Shintaro T. Suzuki, Shuichi Obata, Miwako Fujiwara, Jun-ichi Fujisawa, Shinji Hirano
  • Journal Title: Cell and Tissue Research Volume: 未定 Issue: 1 Pages: 127-148
  • DOI: 10.1007/s00441-021-03448-1
  • Peer Reviewed
• [Journal Article] Reorganization of longitudinal compartments in the laterally protruding paraflocculus of the postnatal mouse cerebellum. (2019)
  • Author(s): Panezai SK, Luo Y, Vibulyaseck S, Sarpong GA, Nguyen-Minh VT, Nedelescu H, Hirano S, Sugihara I.
  • Journal Title: J Comp Neurol. Volume: 1 Issue: 10 Pages: 1-10
  • DOI: 10.1002/cne.24849
  • Peer Reviewed / Open Access
• [Journal Article] Cerebellar modules in the olivo-cortico-nuclear loop demarcated by pcdh10 expression in the adult mouse (2018)
  • Author(s): Sarpong Gideon A.、Vibulyaseck Suteera、Luo Yuanjun、Biswas Mohammad S.、Fujita Hirofumi、Hirano Shinji、Sugihara Izumi
  • Journal Title: Journal of Comparative Neurology Volume: 526 Issue: 15 Pages: 2406-2427
  • DOI: 10.1002/cne.24499
  • Peer Reviewed / Int'l Joint Research
• [Presentation] 情動系神経回路における自閉症関連遺伝子 Pcdh9 の機能 (2019)
  • Author(s): 上村 允人、古瀬 民生、山田 郁子、岡野 圭子、田村 勝、平野 伸二
  • Organizer: 日本分子生物学会
• [Presentation] Deficiency of Protocadherin 1 cell adhesion molecule enhances social behavior in mice. (2018)
  • Author(s): Shinji Hirano, Tamio Furuse, Shungo Hayashizaki, Keiko Okano-Imai, Shigeharu Wakana
  • Organizer: Neuroscience 2018 (Annual meeting of Society for Neuroscience)
  • Int'l Joint Research
• [Presentation] Cerebellar modules in the olivo-cortico-nuclear loop labeled by pcdh10 expression in the adult mouse (2018)
  • Author(s): G. A. SARPONG, S. VIBULYASECK, Y. LUO, M. S. BISWAS, H. FUJITA, S. HIRANO, I. SUGIHARA
  • Organizer: Neuroscience 2018 (Annual meeting of Society for Neuroscience)
  • Int'l Joint Research