移動神経細胞の挙動制御

• Project/Area Number: 18021033
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Keio University
• Principal Investigator: 仲嶋 一範 Keio University, 医学部, 教授 (90280734)
• Project Period (FY): 2006 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥7,200,000 (Direct Cost: ¥7,200,000); Fiscal Year 2007: ¥3,700,000 (Direct Cost: ¥3,700,000); Fiscal Year 2006: ¥3,500,000 (Direct Cost: ¥3,500,000)
• Keywords: 大脳皮質 / 神経細胞移動 / 基底核原基 / 抑制性神経細胞 / 発生分化 / 細胞移動 / マイクロアレイ / 神経細胞

Research Abstract

大脳皮質の抑制性神経細胞は、基底核原基と呼ばれる腹側の領域で誕生し、長い距離を接線方向に移動して皮質に進入する。我々はこれまでに、尾側基底核原基(CGE)由来の細胞は内側基底核原基(MGE)や外側基底核原基(LGE)由来の細胞と異なり一気に尾側に向かって移動するものが主であることを見いだし、caudal migratory stream(CMS)と命名した。従来CGEに特異的に発現する分子の存在は知られていなかったため、次に、各々に由来する細胞の挙動が異なるCGE、MGE、LGEの各領域を切り出し、Microarrayを用いて比較解析をした。その結果、CGE特異的に発現する因子として転写因子COUP-TFIIを同定した。そこで、CGEの細胞においてCOUP-TFIIの発現を阻害(knockdown)し、別の脳のCGE領域に移植して観察したところ、CMSの方向へ移動する細胞の割合が有意に減少することが観察された。また、MGEの細胞にCOUP-TFIIの強制発現ベクターまたはコントロールベクターを導入し、別の脳のCGE領域に移植して、その後の挙動を観察した結果、コントロールベクターを導入されたMGE細胞は移植部位であるCGEから大脳皮質全体に広く移動したのに対し、COUP-TFIIを発現したMGE細胞はCMSの方向へと移動するものが多く観察された。以上の結果は、COUP-TFIIが、CGE由来細胞の細胞移動であるCMSに必要であると共に、MGE由来細胞にCMS方向へと移動させる性質を付与する十分な能力を持っていることを示唆する。

Research Products

• [Journal Article] Migratory behavior of presumptive interneurons is affected by AMPA receptor activation in slice cultures of embryonic mouse neocortex. (2008)
  • Author(s): Masato Yozu
  • Journal Title: Dev. Neurosci. 30 Pages: 105-116
  • Peer Reviewed
• [Journal Article] Identification of molecules preferentially expressed beneath the marginal zone in the developing cerebral cortex. (2008)
  • Author(s): Kashiko Tachikawa
  • Journal Title: Neurosci. Res. 60 Pages: 135-146
  • Peer Reviewed
• [Journal Article] Time constraints and positional cues in the developing cerebellum regulate Purkinje cell placement in the cortical architecture. (2008)
  • Author(s): Barbara Carletti
  • Journal Title: Dev. Biol. (in press)
  • Peer Reviewed
• [Journal Article] The cortical subventricular zone-specific molecule Svetl is part of the nuclear RNA coded by the putative Netrin receptor gene Unc5d and is expressed in multipolar migrating cells. (2008)
  • Author(s): Shinji Sasaki
  • Journal Title: Mol. Cell. Neurosci. (in press)
  • Peer Reviewed
• [Journal Article] Labeling embryonic mouse central nervous system cells by in utero electroporation. (2008)
  • Author(s): Hidenori Tabata
  • Journal Title: Develop. Growth Differ. (in press)
  • Peer Reviewed
• [Journal Article] Cell-autonomous roles of ARX in cell proliferation and neuronal migration during corticogenesis. (2008)
  • Author(s): Gaelle Friocourt
  • Journal Title: J. Neurosci. (in press)
  • Peer Reviewed
• [Journal Article] 神経細胞の移動と層構造形成の制御機構 (2008)
  • Author(s): 宇都飛鳥
  • Journal Title: 蛋白質 核酸 酵素 53 Pages: 365-372
• [Journal Article] Cdk5 is required for multipolar-to-bipolar transition during radial neuronal migration and proper dendrite development of pyramidal neurons in the cerebral cortex (2007)
  • Author(s): Toshio Ohshima
  • Journal Title: Development 134 Pages: 2273-2282
  • Peer Reviewed
• [Journal Article] The extremely conserved C-terminal region of Reelin is not necessary for secretion but is required for efficient activation of downstream signaling. (2007)
  • Author(s): Yoshimi Nakano
  • Journal Title: J. Biol. Chem. 282 Pages: 20544-20552
  • Peer Reviewed
• [Journal Article] Control of tangential/non-radial migration of neurons in the developing cerebral cortex. (2007)
  • Author(s): Kazunori Nakajiama
  • Journal Title: Neurochem. Int. 51 Pages: 121-131
  • Peer Reviewed
• [Journal Article] Regulation of the interaction of Disabled-1 with CIN85 by phosphorylation with Cyclin-dependent kinase 5. (2007)
  • Author(s): Yutaka Sato
  • Journal Title: Genes to Cells 12 Pages: 1315-1327
  • Peer Reviewed
• [Journal Article] Computational cell model based on autonomous cell movement regulated by cell-cell signalling successfully recapitulates the "inside and outside"pattern of cell sorting. (2007)
  • Author(s): Takuya T. Maeda
  • Journal Title: BMC Syst. Biol. 1
  • Peer Reviewed
• [Journal Article] 子宮内電気穿孔法による蛍光タンパク質の遺伝子導入技術 (2007)
  • Author(s): 田畑秀典
  • Journal Title: バイオテクノロジージャーナル 7 Pages: 489-495
• [Journal Article] Expression profiles of Insulin-like growth factor binding protein-like 1 in the developing mouse forebrain (2007)
  • Author(s): Yuko Gonda
  • Journal Title: Gene Expr. Patterns 7 (4) Pages: 431-440
• [Journal Article] Migratory behavior of presumptive interneurons is affected by AMPA receptor activation in slice cultures of embryonic mouse neocortex (2007)
  • Author(s): Masato Yozu
  • Journal Title: Dev. Neurosci. (In press)
• [Journal Article] Cdk5 is required for multipolar-to-bipolar transition during radial neuronal migration and proper dendrite development of pyramidal neurons in the cerebral cortex (2007)
  • Author(s): Toshio Ohshima
  • Journal Title: Development (In press)
• [Journal Article] 発生期大脳皮質におけるニューロンの移動と配置のダイナミクス (2007)
  • Author(s): 森本桂子
  • Journal Title: 実験医学 25 (3) Pages: 338-345
• [Journal Article] Large-scale correlation of DNA accession numbers to the cDNAs in the FANTOM full-length mouse cDNA clone set (2006)
  • Author(s): Itsuki Ajioka
  • Journal Title: Keio J. Med. 55 (3) Pages: 107-110
• [Journal Article] Mouse Disabled1 (Dab1) is a nucleocytoplasmnic shuttling protein (2006)
  • Author(s): Takao Honda
  • Journal Title: J. Biol. Chem. 281 (50) Pages: 38951-38965
• [Journal Article] 大脳皮質層形成機構の解明とその応用 (2006)
  • Author(s): 味岡逸樹
  • Journal Title: 再生医療-日本再生医療学会雑誌 5 (4) Pages: 476-482
• [Journal Article] 脳室の構造 (2006)
  • Author(s): 仲嶋一範
  • Journal Title: Clinical Neuroscience 24 (11) Pages: 1204-1208
• [Presentation] Dynamics of cerebral cortical development (2008)
  • Author(s): Kazunori Nakajima
  • Organizer: 熊本大学発生医学研究センターグローバルCOEリエゾンラボ研究会
  • Place of Presentation: 熊本
  • Year and Date: 2008-01-30
• [Presentation] Neuronal migration in the developing cerebral cortex-Development and application of in utero electroporation (2008)
  • Author(s): Kazunori Nakajima
  • Organizer: 自然科学研究機構基礎生物学研究所研究会:「遺伝子導入法の神経研究への応用」、
  • Place of Presentation: 岡崎
• [Presentation] Identification of molecules preferentially expressed in restricted regions in the developing telencephalon (2008)
  • Author(s): Kazunori Nakajima
  • Organizer: 自然科学研究機構基礎生物学研究所研究会:「大脳皮質の発生と可塑性II」
  • Place of Presentation: 岡崎
• [Presentation] Dynamics of neuronal migration and layer formation in the developing cerebral cortex (2007)
  • Author(s): Kazunori Nakajima
  • Organizer: Developmental Biology Special Seminar, The Children's Hospital of Philadelphia
  • Place of Presentation: Philadelphia
  • Year and Date: 2007-11-01
• [Presentation] 脳の発生過程における神経細胞のダイナミクス (2007)
  • Author(s): 仲嶋一範
  • Organizer: 生命科学イメージングシンポジウム〜分子動態から発生・疾患の解明へ〜
  • Place of Presentation: 東京
  • Year and Date: 2007-10-16
• [Presentation] 大脳皮質構造の発生分化機構 (2007)
  • Author(s): 仲嶋一範
  • Organizer: 聖マリアンナ医科大学フロンティア医科学大学院セミナー
  • Place of Presentation: 川崎
  • Year and Date: 2007-07-11
• [Presentation] 大脳皮質神経細胞構築のダイナミクス (2007)
  • Author(s): 仲嶋一範
  • Organizer: 国立精神神経センター神経研究所セミナー
  • Place of Presentation: 小平
  • Year and Date: 2007-07-03
• [Presentation] 皮質脳室帯に由来する2つの集団が示す互いに異なった移動過程 (2007)
  • Author(s): 田畑秀典
  • Organizer: 第35回慶應ニューロサイエンス研究会
  • Place of Presentation: 東京
  • Year and Date: 2007-06-09
• [Presentation] 神経細胞移動と皮質層形成の制御機構 (2007)
  • Author(s): 仲嶋一範
  • Organizer: 近畿大学理工学部生命科学科セミナー
  • Place of Presentation: 東大阪
  • Year and Date: 2007-04-19
• [Presentation] 脳の細胞構築のメカニズム (2007)
  • Author(s): 仲嶋一範
  • Organizer: 大阪市立大学大学院医学研究科セミナー
  • Place of Presentation: 大阪
  • Year and Date: 2007-04-18
• [Presentation] Neuronal migration and layer formation in the developing cerebral cortex (2007)
  • Author(s): Kazunori Nakajima
  • Organizer: International Meeting "Neurogenesis 2007"
  • Place of Presentation: Tokyo
• [Presentation] 発生期大脳皮質における神経細胞移動と層形成の制御 (2007)
  • Author(s): 仲嶋一範
  • Organizer: 第30回日本神経科学大会・第50回日本神経化学会大会・第17回日本神経回路学会大会合同大会(Neuro2007)
  • Place of Presentation: 横浜
• [Presentation] Screening and functional analyses of the molecules that are preferentially expressed in the caudal ganglionic eminence in the developing mouse brain. (2007)
  • Author(s): Shigeaki Kanatani
  • Organizer: Society for Neuroscience, 37th Annual Meeting
  • Place of Presentation: San Diego
• [Presentation] 大脳皮質発生における神経細胞移動と層形成の制御機構 (2007)
  • Author(s): 仲嶋一範
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学会大会合同大会(BMB2007)
  • Place of Presentation: 横浜
• [Book] In utero electroporation; assay system for migration of cerebral cortical neurons Electroporation and Sonoporation in Developmental Biology (2008)
  • Author(s): Hidenori Tabata
  • Publisher: Springer(In press)
• [Book] リーリン KEY WORD 精神 第4版 (2007)
  • Author(s): 関根克敏
  • Publisher: 先端医学社
• [Book] Neurogenesis Encyclopedic Reference of Neuroscience (2007)
  • Author(s): Koji Oishi
  • Publisher: Springer-Verlag(In press)
• [Book] リーリンKEY WORD 精神 第4版
  • Author(s): 関根克敏
  • Publisher: 先端医学社(印刷中)