二次嗅覚メゾ回路の抽出

• Project Area: Mesoscopic neurocircuitry: towards understanding of the functional and structural basis of brain information processing
• Project/Area Number: 23115517
• 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: National Institute of Genetics
• Principal Investigator: 平田 たつみ 国立遺伝学研究所, 総合遺伝研究系, 准教授 (80260587)
• Project Period (FY): 2011-04-01 – 2013-03-31
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥11,050,000 (Direct Cost: ¥8,500,000、Indirect Cost: ¥2,550,000); Fiscal Year 2012: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2011: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
• Keywords: 嗅覚系 / 軸索投射 / 神経回路 / マウス

Outline of Annual Research Achievements

一次嗅覚神経回路は匂い情報を空間的に選別して、嗅球に「匂い地図」を作り上げるが、その地図がその後どのように処理されているかは全くの謎である。本研究では、二次嗅覚神経回路を、嗅球神経細胞の軸索に対するガイド制御の違いに着目して、メゾ回路に分解することをめざした。本年度の主な成果は以下の3つである。
1. 誕生日依存的な嗅球軸索投射パターンを調べるために最適なトランスジェニック動物を開発した。神経細胞が分化直後に一過的に発現する遺伝子４つを選択し、この遺伝子座に活性誘導可能なCreER recombinaseを組換えたBACトランスジェニックマウスを19系統作成した。この中には、非常に効率よく神経細胞の誕生日依存的にloxP配列の組み替えを誘導できるものが複数含まれており、今後の解析に非常に有効であると期待できる。
2. 浜松医科大学福田敦夫教授との班員間共同研究により、伸長中の嗅球軸索とこの軸索をガイドする道標細胞との間に、発生期一過的なシナプス伝達が存在する事を見いだした。他の神経系において、このような軸索と道標細胞との間の神経活動依存的な相互作用が、最終的な神経回路形成を制御する事が知られており興味深い。この共同研究成果について論文発表した。
3. ノックアウトマウスを用いた解析により、主嗅球と副嗅球軸索のガイドに反発性軸索ガイド因子受容体neuropilin2が重要な機能を果たす事を見いだした。

Research Progress Status

24年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

24年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] Neocortical neurogenesis is not really “neo”: a new evolutionary model derived from a comparative study of chick pallial development. (2013)
  • Author(s): I.K. Suzuki
  • Journal Title: Dev. Growth Differ. (review) Volume: 55 Issue: 1 Pages: 173-187
  • DOI: 10.1111/dgd.12020
  • Peer Reviewed
• [Journal Article] Guidepost neurons for the lateral olfactory tract : expression of metabotropic glutamate receptor 1 and linnervation by glutamatergic olfactory bulb axons (2012)
  • Author(s): Hirata, T., Kumada, T., Kawasaki, T., Furukawa, T., Aiba, A., Conquet, F., Saga, Y. and Fukuda, A.
  • Journal Title: Dev. Neurobiol Volume: (in press) Issue: 12 Pages: 1559-1576
  • DOI: 10.1002/dneu.22030
  • Peer Reviewed
• [Journal Article] Evolutionary conservation of neocortical neurogenetic program in the mammals and birds (2012)
  • Author(s): I.K. Suzuki
  • Journal Title: BioArchitecture (review) Volume: 2 Issue: 4 Pages: 1-6
  • DOI: 10.4161/bioa.21032
  • Peer Reviewed
• [Journal Article] Updated interpretation of the principles of neural development (2012)
  • Author(s): T. Hirata
  • Journal Title: Development (book review) Volume: 139 Issue: 24 Pages: 5-6
  • DOI: 10.1242/dev.084632
  • Peer Reviewed
• [Journal Article] The Temporal Sequence of the Mammalian Neocortical Neurogenetic Program Drives Mediolateral Pattern in the Chick Pallium (2012)
  • Author(s): Suzuki, I.
  • Journal Title: Developmental Cell Volume: 22 Issue: 4 Pages: 1-8
  • DOI: 10.1016/j.devcel.2012.01.004
  • Peer Reviewed
• [Journal Article] Induction of axon growth arrest without growth cone collapse through the N-terminal region of four-transmembrane glycoprotein M6a (2011)
  • Author(s): Y.Sato
  • Journal Title: Dev.Neurobiol. Volume: 71 Issue: 9 Pages: 733-746
  • DOI: 10.1002/dneu.20941
  • Peer Reviewed
• [Journal Article] Cartilage acidic protein-1B(LOTUS), an endogenous Nogo receptor antagonist for axon tract formation (2011)
  • Author(s): Sato, Y., Iketani, M., Kurihara, Y., Yamaguchi, M., Yamashita, N., Nakamura, F., Arie, Y., Kawasaki, T., Hirata, T., Abe, T., Kiyonari, H., Strittmatter, S. M., Goshima, Y. and Takei, K.
  • Journal Title: Science Volume: Vol.333 Issue: 6043 Pages: 769-773
  • DOI: 10.1126/science.1204144
  • Peer Reviewed
• [Journal Article] Actin-independent behavior and membrane deformation exhibited by the four-transmembrane protein M6a (2011)
  • Author(s): Y.Sato
  • Journal Title: PLoS One Volume: e26702 Issue: 12 Pages: 1-13
  • DOI: 10.1371/journal.pone.0026702
  • Peer Reviewed
• [Presentation] The making of the mammalian neocortex (2013)
  • Author(s): T. Hirata
  • Organizer: CDB Symposium #8211; The Making of a Vertebrate
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2013-03-04
  • Invited
• [Presentation] Neocortical neurogenesis is not really “neo”: a new evolutionary model derived from a comparative study of the chick pallial development (2012)
  • Author(s): I.K. Suzuki
  • Organizer: 7th International Chick Meeting
  • Place of Presentation: Nagoya, Japan
  • Year and Date: 2012-11-14
  • Invited
• [Presentation] Axon Outgrowth Regulated by Four-Transmembrane Protein M6a (2012)
  • Author(s): T. Hirata
  • Organizer: US/Japan Brain Research Cooperative Program. Growth cones and axon regeneration entering the age of informatics
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2012-10-10
  • Invited
• [Presentation] Mammalian-type neurogenetic potential in chick pallial neural progenitors (2012)
  • Author(s): T. Hirata
  • Organizer: Symposium “Circuit Construction in the Mammalian Cerebral Cortex: Genetic and Imaging Approaches”
  • Place of Presentation: Mishima, Japan
  • Invited
• [Presentation] M6 proteins regulate axon outgrowth in mouse callosal neurons (2011)
  • Author(s): S.Mita
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-13
• [Presentation] Generation program of neocortical layer-specific neurons predates mammalian emergence (2011)
  • Author(s): I.K.Suzuki
  • Organizer: Society for Molecular Biology and Evolution
  • Place of Presentation: 京都(招待講演)
  • Year and Date: 2011-07-28
• [Presentation] Distinct functions of PInA family in the central olfactory projection (2011)
  • Author(s): T.Kawasaki
  • Organizer: 第44回日本発生生物学会年会
  • Place of Presentation: 沖縄
  • Year and Date: 2011-05-20