Elucidation of developmental mechanisms of the cerebral cortex focusing on axon guidance

• Project/Area Number: 16H04654
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurophysiology / General neuroscience
• Research Institution: Kanazawa University
• Principal Investigator: Shinmyo Yohei 金沢大学, 医学系, 准教授 (00418831)
• Co-Investigator(Kenkyū-buntansha): 河崎 洋志 金沢大学, 医学系, 教授 (50303904)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000); Fiscal Year 2018: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2016: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
• Keywords: 軸索ガイダンス / Draxin / マウス / フェレット / 神経回路 / draxin / 神経科学

Outline of Final Research Achievements

To understand molecular mechanisms of the neural circuit formation in the cerebral cortex, we investigated functions of an axon guidance molecule, Draxin. We found that in addition to the receptors Dcc and Neogenin, heparan sulfate proteoglycan was important for the activity of Draxin. Furthermore, for the purpose of elucidating molecular mechanisms of the neural circuit formation in the cerebral cortex of higher mammals, we established a gene knockout method by combining in utero electroporation with the CRISPR/Cas9 system in ferrets.

Academic Significance and Societal Importance of the Research Achievements

本研究の成果は、大脳皮質の神経回路形成機構の解明のみならず、臨床脳医学にも大きく貢献できる。ヒト大脳皮質形成異常に見られるてんかんや発達遅滞の発症メカニズムには不明な点が多く、根本的な治療法は確立されていないのが現状である。本研究成果は、大脳皮質形成異常の病態機序解明および治療薬探索に繋がることが期待できる。

Research Products

• [Journal Article] Three-dimensional evaluation of murine ovarian follicles using a modified CUBIC tissue clearing method. (2018)
  • Author(s): Kagami K., Shinmyo Y., Ono M., Kawasaki H. and Fujiwara H.
  • Journal Title: Reproductive Biology and Endocrinology Volume: 16 Issue: 1 Pages: 72-72
  • DOI: 10.1186/s12958-018-0381-7
  • Peer Reviewed / Open Access
• [Journal Article] The chemorepellent draxin is involved in hippocampal mossy fiber projection. (2018)
  • Author(s): Tawarayama H, Yamada H, Shinmyo Y, Tanaka H, Ikawa S.
  • Journal Title: Biochem Biophys Res Commun. Volume: 500 Issue: 2 Pages: 217-223
  • DOI: 10.1016/j.bbrc.2018.04.043
  • Peer Reviewed / Open Access
• [Journal Article] Distribution and morphological features of microglia in the developing cerebral cortex of gyrencephalic mammals (2018)
  • Author(s): Mizuguchi K., Horiike T., Matsumoto N., Ichikawa Y., Shinmyo Y. and Kawasaki H.
  • Journal Title: Neurochemical Research Volume: 43 Issue: 5 Pages: 1075-1085
  • DOI: 10.1007/s11064-018-2520-0
  • Description: 掲載確定 印刷中
  • Peer Reviewed
• [Journal Article] CRISPR/Cas9-mediated gene knockout in the mouse brain using in utero electroporation (2017)
  • Author(s): Shinmyo Y. and Kawasaki H.
  • Journal Title: Current Protocols in Neuroscience Volume: 79 Issue: 1
  • DOI: 10.1002/cpns.26
  • NAID: 120005764199
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Folding of the Cerebral Cortex Requires Cdk5 in Upper-Layer Neurons in Gyrencephalic Mammals (2017)
  • Author(s): Shinmyo Yohei、Terashita Yukari、Dinh Duong Tung Anh、Horiike Toshihide、Kawasumi Muneo、Hosomichi Kazuyoshi、Tajima Atsushi、Kawasaki Hiroshi
  • Journal Title: Cell Rep Volume: 20 Issue: 9 Pages: 2131-2143
  • DOI: 10.1016/j.celrep.2017.08.024
  • NAID: 120006374153
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] CRISPR/Cas9-mediated gene knockout in the mouse brain using in utero electroporation (2016)
  • Author(s): Shinmyo Y., Tanaka S., Tsunoda S., Hosomichi K., Tajima A. and Kawasaki H.
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 20611-20611
  • DOI: 10.1038/srep20611
  • NAID: 120005764199
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] An essential role of SVZ progenitors in cortical folding in gyrencephalic mammals (2016)
  • Author(s): Toda T., Shinmyo Y., Dinh D. T. A., Masuda K. and Kawasaki H.
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 29578-29578
  • DOI: 10.1038/srep29578
  • NAID: 120005850359
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] An essential role of SVZ progenitors in cortical folding in gyrencephalic mammals. (2017)
  • Author(s): Yohei Shinmyo, Tomohisa Toda, Dinh Tung Anh Duong, Kosuke Masuda and Hiroshi Kawasaki.
  • Organizer: 日本神経科学大会