Analysis of the dendrite formation mechanism by Reelin-Dab1 signaling pathway

• Project/Area Number: 24700357
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Keio University
• Principal Investigator: Honda Takao 慶應義塾大学, 医学部, 助教 (30365225)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: Reelin / Dab1 / reeler / yotari / NLS / NES / 核細胞質間シャトリング / 樹状突起形成 / 樹状突起 / reelin / dab1

Outline of Final Research Achievements

As we have found that Dab1 is involved in dendrite formation and is subject to nucleocytoplamic shuttling, we hypothesized that Dab1 might regulate the dendrite formation through the regulation of gene expression. To examine this hypothesis, we expressed a candidate gene to dab1-knockdonwed neurons, and found that a candidate gene could partially rescue the abnormal dendrite formation. Because of no significant difference in Dab1 protein amount in reeler, we next examined whether the candidate molecule could enhance a putative dendrite formation signal by Dab1-signaling pathway. Dissociated neurons with or without knockdown plasmids against the candidate molecule were treated with Reelin, and Dab1 tyrosine phosphorylation, a plausible target of the candidate molecule, was compared. However, we could not detect a significant difference of the level, suggesting that the dendrite formation rescue effects by the candidate molecule might be caused by other regulation mechanism.

Research Products

• [Journal Article] The COUP-TFII/Neuropilin-2 is a molecular switch steering diencephalon-derived GABAergic neurons in the developing mouse brain (2015)
  • Author(s): Shigeaki Kanatani, Takao Honda, Michihiko Aramaki, Kanehiro Hayashi, Ken-ichiro Kubo, Mami Ishida, Daisuke H. Tanaka, Takeshi Kawauchi, Katsutoshi Sekine, Sayaka Kusuzawa, Takahiko Kawasaki, Tatsumi Hirata, Hidenori Tabata, Per Uhlen and Kazunori Nakajima
  • Journal Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 112(36) Issue: 36
  • DOI: 10.1073/pnas.1420701112
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Importance of Reelin C-Terminal Region in the Development and Maintenance of the Postnatal Cerebral Cortex and Its Regulation by Specific Proteolysis (2015)
  • Author(s): Takao Kohno, Takao Honda,Ken-ichiro Kubo, Yoshimi Nakano, Ayaka Tsuchiya, Tatsuro Murakami, Hideyuki Banno, Kazunori Nakajima, and Mitsuharu Hattori
  • Journal Title: The Journal of Neuroscience Volume: 35(11) Issue: 11 Pages: 4776-4787
  • DOI: 10.1523/jneurosci.4119-14.2015
  • Peer Reviewed / Open Access
• [Journal Article] Characterization of the dipeptide repeat protein in the molecular pathogenesis of c9FTD/ALS (2015)
  • Author(s): Mai Yamakawa, Daisuke Ito, Takao Honda, Ken-ichiro Kubo, Mariko Noda, Kazunori Nakajima, and Norihiro Suzuki
  • Journal Title: Hum. Mol. Genet. Volume: 24 Issue: 6 Pages: 1630-1645
  • DOI: 10.1093/hmg/ddu576
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Reelin receptors ApoER2 and VLDLR are expressed in distinct spatio-temporal patterns in developing mouse cerebral cortex. (2014)
  • Author(s): Hirota Y, Kubo K, Katayama K, Honda T, Fujino T, Yamamoto TT and Nakajima K
  • Journal Title: J. Comp. Neurol Volume: 523(3) Issue: 3 Pages: 463-78
  • DOI: 10.1002/cne.23691
  • Peer Reviewed
• [Journal Article] Reelin controls neuronal positioning by promoting cell-matrix adhesion via inside-out activation of integrin α5β 1 (2012)
  • Author(s): Katsutoshi Sekine, Takeshi Kawauchi, Ken-ichiro Kubo, Takao Honda, Joachim Herz, Mitsuharu Hattori, Tatsuo Kinashi, and Kazunori Nakajima
  • Journal Title: Neuron Volume: 76(2) Issue: 2 Pages: 353-369
  • DOI: 10.1016/j.neuron.2012.07.020
  • Peer Reviewed
• [Journal Article] Leucine-rich glioma inactivated 1 (Lgi1), an epilepsy-related secreted protein, has a nuclear localization signal and localizes both to the cytoplasm and nucleus of the caudal ganglionic eminence neurons. (2012)
  • Author(s): Sayaka Kusuzawa, Takao Honda, Yuko Fukata, Masaki Fukata, Shigeaki Kanatani, Daisuke H. Tanaka, and Kazunori Nakajima
  • Journal Title: Eur. J. Neurosci. Volume: 36 Issue: 3 Pages: 2284-2292
  • DOI: 10.1111/j.1460-9568.2012.08129.x
  • Peer Reviewed
• [Presentation] Analysis of the role of Dab1 nucleo-cytoplasmic transport for migration of excitatory neurons (Dab1の核細胞質間輸送が興奮性神経細胞の移動に果たす役割の解明) (2016)
  • Author(s): Takao Honda and Kazunori Nakajima
  • Organizer: 第９回神経発生討論会・難治疾患共同研究拠点共同開催学術集会
  • Place of Presentation: 東京医科歯科大学Ｍ＆Ｄタワー鈴木章夫記念講堂（東京都、文京区）
  • Year and Date: 2016-03-18
• [Presentation] C-terminal region of Reelin is required for development and maintenance of the postnatal cerebral cortex and its functions are regulated by specific proteolysis (2016)
  • Author(s): Takao Kohno, Takao Honda, Ken-ichiro Kubo, Yoshimi Nakano, Ayaka Tsuchiya, Tatsuro Murakami, Hideyuki Banno, Kazunori Nakajima, and Mitsuharu Hattori
  • Organizer: 新学術領域研究「神経細胞の多様性と大脳新皮質の構築」第3回国際シンポジウム「Neocortical Organization 3」
  • Place of Presentation: 東京大学小柴ホール（東京都、文京区）
  • Year and Date: 2016-02-11
  • Int'l Joint Research
• [Presentation] Dab1核細胞質間シャトリングの大脳新皮質層形成における役割の解明 (2015)
  • Author(s): 本田岳夫、仲嶋一範
  • Organizer: 日本解剖学会関東支部 第103回学術集会
  • Place of Presentation: 慶應義塾大学日吉キャンパス（神奈川県、横浜市）
  • Year and Date: 2015-11-07
• [Presentation] 二つの核移行経路による細胞質Dab1量の適切な調節が興奮性神経細胞移動に重要である (2015)
  • Author(s): 本田岳夫、仲嶋一範
  • Organizer: 第50回慶應ニューロサイエンス研究会「システムとしての脳の理解と介入」
  • Place of Presentation: 慶應義塾大学信濃町キャンパス（東京都、新宿区）
  • Year and Date: 2015-10-31
• [Presentation] Importance of Reelin C-terminal region in the development and maintenance of the postnatal cerebral cortex and its regulation by specific proteolysis (2015)
  • Author(s): Takao Kohno, Takao Honda, Ken-ichiro Kubo, Yoshimi Nakano, Ayaka Tsuchiya, Tatsuro Murakami, Hideyuki Banno, Kazunori Nakajima, and Mitsuharu Hattori.
  • Organizer: Society for Neuroscience, Neuroscience 2015 meeting
  • Place of Presentation: McCormick Place, Chicago, U.S.A.
  • Year and Date: 2015-10-17
  • Int'l Joint Research
• [Presentation] 二つの核移行経路による細胞質Dab1量の適切な調節が大脳皮質ニューロンの移動に重要である（Proper level of cytosolic Disabled-1, which is regulated by dual nuclear translocation pathways, is important for cortical neuronal migration） (2015)
  • Author(s): 本田岳夫、仲嶋一範
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 神戸国際会議場・神戸国際展示場（兵庫県、神戸市）
  • Year and Date: 2015-07-28
• [Presentation] 巨大分泌蛋白質リーリンのC末端領域を介した大脳皮質形成機構 (2015)
  • Author(s): 河野孝夫、本田岳夫、久保健一郎、中野良美、土屋綾香、村上達郎、阪野英幸、仲嶋一範、服部光治
  • Organizer: 第61回日本薬学会東海支部総会・大会
  • Place of Presentation: 名古屋市立大学（愛知県、名古屋市）
  • Year and Date: 2015-07-04
• [Presentation] Evidence of a link between TDP-43 and dipeptide repeat protein in c9FTD/ALS (2015)
  • Author(s): Mai Yamakawa, Daisuke Ito, Takao Honda, Ken-ichiro Kubo, Mariko Noda, and Kazunori Nakajima, and Norihiro Suzuki
  • Organizer: 第56回日本神経学会学術大会
  • Place of Presentation: 朱鷺メッセ（新潟県、新潟市）
  • Year and Date: 2015-05-20
• [Presentation] Distinct localization patterns of Reelin receptors ApoER2 and VLDLR in developing mouse cerebral cortex (2015)
  • Author(s): Yuki Hirota, Ken-ichiro Kubo, Kei-ichi Katayama, Takao Honda, Takahiro Fujino, Tokuo T. Yamamoto, and Kazunori Nakajima
  • Organizer: 第49回慶應ニューロサイエンス研究会
  • Place of Presentation: 慶應義塾大学信濃町キャンパス、東京
  • Year and Date: 2015-02-21
• [Presentation] The novel function of Reelin in the dendrite development and layer formation in the postnatal brain (2014)
  • Author(s): Takao Kohno, Takao Honda, Ken-ichiro Kubo, Yoshimi Nakano, Ayaka Tsuchiya, Tatsuro Murakami, Hideyuki Banno, Kazunori Nakajima, and Mitsuharu Hattori
  • Organizer: Society for Neuroscience, Neuroscience 2014 Meeting
  • Place of Presentation: Washington, D.C., U.S.A.
  • Year and Date: 2014-11-15 – 2024-11-19
• [Presentation] リーリン受容体ApoER2とVLDLRの大脳皮質形成過程における発現と機能 (2014)
  • Author(s): 廣田ゆき、久保健一郎、本田岳夫、藤野貴広、山本徳男、仲嶋一範
  • Organizer: 第36回日本生物学的精神医学会・第57回日本神経化学会大会
  • Place of Presentation: 奈良県文化会館・奈良県新公会堂、奈良（奈良県）
  • Year and Date: 2014-09-29 – 2014-10-01
• [Presentation] The novel proteolytic cleavage of Reelin near C-terminus regulates postnatal neuronal development (2013)
  • Author(s): Takao Kohno, Takao Honda, Ken-ichiro Kubo, Yoshimi Nakano, Tatsuro Murakami, Kazunori Nakajima, and Mitsuharu Hattori
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: パシフィコ横浜（横浜）
• [Presentation] 大脳新皮質層形成に必須のDab1はImportin依存性または非依存性に核移行する (2013)
  • Author(s): 本田岳夫、仲嶋一範
  • Organizer: 第36回日本神経科学大会・第56回日本神経化学会大会・第23回日本神経回路学会大会合同大会（Neuro2013）
  • Place of Presentation: 国立京都国際会館（京都）
• [Presentation] 発生期大脳皮質においてリーリンはそのシグナル下流分子を通して神経細胞の凝集を誘導する (2013)
  • Author(s): 久保健一郎、関根克敏、山川眞以、石井一裕、野田万理子、廣田ゆき、本田岳夫、林周宏、仲嶋一範
  • Organizer: 第36回日本神経科学大会・第56回日本神経化学会大会・第23回日本神経回路学会大会合同大会（Neuro2013）
  • Place of Presentation: 国立京都国際会館（京都）
• [Presentation] 脳の形成を司る細胞外因子リーリンのプロテオリシスによる機能制御機構の解明 (2013)
  • Author(s): 河野孝夫、本田岳夫、久保健一郎、中野良美、村上達郎、仲嶋一範、服部光治
  • Organizer: 平成25年度 生理学研究所 研究会「シナプス恒常性維持の分子基盤とその破綻」
  • Place of Presentation: 生理学研究所（岡崎）
• [Presentation] 大脳新皮質構築を制御するDab1の核移行メカニズムの解析（Analysis of the nucleocytoplasmic shuttling of Dab1, an essential protein for the neocortical development） (2012)
  • Author(s): 本田岳夫
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋
• [Presentation] 大脳新皮質層形成に必須のDab1はImportin依存性または非依存性に核移行する
  • Author(s): 本田岳夫、仲嶋一範
  • Organizer: 第４６回慶應ニューロサイエンス研究会
  • Place of Presentation: 慶應義塾大学信濃町キャンパス（東京）
• [Remarks] 慶應義塾大学医学部解剖学教室仲嶋研究室ホームページ
  • URL: http://plaza.umin.ac.jp/~Nakajima/index.html