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Ligand dependent Notch activity and its funciton during vertebrate development.

Research Project

Project/Area Number 24370080
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Cell biology
Research InstitutionChiba University

Principal Investigator

MOTOYUKI ITOH  千葉大学, 薬学研究科(研究院), 教授 (20377906)

Co-Investigator(Renkei-kenkyūsha) KAWAKAMI koichi  国立遺伝学研究所, 教授 (70195048)
MIZOGUCHI Takamasa  千葉大学, 大学院薬学研究院, 助教 (10645419)
Project Period (FY) 2012-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2014: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2013: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2012: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Keywords細胞分化 / シグナル伝達 / ゼブラフィッシュ / Notch / 発生
Outline of Final Research Achievements

Endocytic proteins such as epsin and dynamin participate in Notch ligand activity by mediating Notch ligand endocytosis. The ubiquitin ligase Mib1 also plays essential roles in Notch signaling via Notch ligand ubiquitination. However, the molecular links between Mib1 and endocytic proteins have not been fully defined. Here, we show that Mib1 modulates dynamin recruitment by regulating the interaction between Snx18 and dynamin 2 to ensure the efficient signaling activity of Notch ligands. During vertebrate development, the spinal cord is a site of sensory and motor tasks coordinated by interneurons and the ongoing neurogenesis. V2-interneuron (V2-IN) progenitors (p2) develop into excitatory V2a-INs and inhibitory V2b-INs. Using zebrafish embryos with altered Notch signaling, we show that V2-IN cell progenitor proliferation and V2a/V2b cell fate determination involve signaling through different sets of Notch ligand-receptor combinations that occur concurrently during development.

Report

(5 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (23 results)

All 2016 2015 2014 2013 2012 Other

All Journal Article (7 results) (of which Peer Reviewed: 6 results,  Acknowledgement Compliant: 3 results,  Open Access: 1 results) Presentation (14 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results) Remarks (2 results)

  • [Journal Article] Mib1 modulates dynamin 2 recruitment via Snx18 to promote Dll1 endocytosis for efficient Notch signaling.2016

    • Author(s)
      Okano M, Matsuo H, Nishimura Y, Hozumi K, Yoshioka S, Tonoki A, Itoh M
    • Journal Title

      Genes Cells

      Volume: 28 FEB Issue: 5 Pages: 1-17

    • DOI

      10.1111/gtc.12350

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Mindbomb 2 is dispensable for embryonic development and Notch signalling in zebrafish2015

    • Author(s)
      Mikami S, Nakaura M, Kawahara A, Mizoguchi T, Itoh M
    • Journal Title

      Biol Open

      Volume: 4 Issue: 11 Pages: 1576-82

    • DOI

      10.1242/bio.014225

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Notch signal.2015

    • Author(s)
      Mizoguchi T. Itoh M
    • Journal Title

      生体の科学

      Volume: 66 Pages: 440-441

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Different combinations of Notch ligands and receptors regulate V2 interneuron progenitor proliferation and V2a/V2b cell fate determination2014

    • Author(s)
      Okigawa, S., Mizoguchi, T., Okano, M., Tanaka, H., Isoda, M., Jiang, Y.J., Suster, M., Higashijima, S.-I., Kawakami, K., and Itoh, M.
    • Journal Title

      Developmental Biology

      Volume: 391 Issue: 2 Pages: 196-206

    • DOI

      10.1016/j.ydbio.2014.04.011

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Target Gene Knockdown by 2',4'-BNA/LNA Antisense Oligonucleotides in Zebrafish2014

    • Author(s)
      Itoh M, Nakaura M, Imanishi T, Obika S
    • Journal Title

      Nucleic Acid Ther.

      Volume: 3 Issue: 3 Pages: 186-191

    • DOI

      10.1089/nat.2013.0464

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] DEAD-Box protein Ddx46 is required for the development of the digestive organs and brain in zebrafish2012

    • Author(s)
      Hozumi S.
    • Journal Title

      PLoS One

      Volume: 7 Issue: 3 Pages: e33675-e33675

    • DOI

      10.1371/journal.pone.0033675

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] NLK positively regulates Wnt/β-catenin signaling by phosphorylating LEF1 in neural progenitor cells2012

    • Author(s)
      Ota, S., Ishitani, S., Shimizu, N., Matsumoto, K., Itoh, M., and Ishitani. T
    • Journal Title

      EMBO J

      Volume: 31 Issue: 8 Pages: 1904-1915

    • DOI

      10.1038/emboj.2012.46

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] Mib1 promotes Dll1 endocytosis and Notch signaling through ubiquitination of Dynamin2 and Snx18.2015

    • Author(s)
      Makoto Okano, Hiromi Matsuo, Yuya Nishimura, Ledi Liu, Katsuto Hozumi, Saho Yoshioka, Ayako Tonoki, Motoyuki Itoh
    • Organizer
      第38回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2015-12-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] Ubiquitination of Dynamin 2 and Snx18 by Mib1 promotes Dll1 endocytosis and Notch signaling.2015

    • Author(s)
      Makoto Okano, Hiromi Matsuo, Yuya Nishimura, Katsuto Hozumi, Saho Yoshioka, Ayako Tonoki, Motoyuki Itoh
    • Organizer
      Notch meeting
    • Place of Presentation
      Athens, Greek.
    • Year and Date
      2015-10-07
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Notch Signaling Regulates V2 Interneuronal Differentiation and Neurite Outgrowth2015

    • Author(s)
      Miku Iihama, Takamasa Mizoguchi, Mizuki Nakaura, Michi Fukada, Miki Chin, Koichi Kawakami, Motoyuki Itoh
    • Organizer
      第21回小型魚類研究会
    • Place of Presentation
      大阪大学銀杏会館
    • Year and Date
      2015-09-19
    • Related Report
      2015 Annual Research Report
  • [Presentation] Mind bomb2 is not essential for Notch signaling.2015

    • Author(s)
      Shohei Mikami, Mizuki Nakaura, Atsuo Kawahara, Takamasa Mizoguchi, Motoyuki Itoh
    • Organizer
      第21回小型魚類研究会
    • Place of Presentation
      大阪大学銀杏会館
    • Year and Date
      2015-09-19
    • Related Report
      2015 Annual Research Report
  • [Presentation] Mib1 ubiquitinates dynamin 2 and Snx18 to promote Dll1 endocytosis in Notch signaling.2015

    • Author(s)
      Makoto Okano、Hiromi Matsuo、Yuya Nishimura、Katsuto Hozumi、Saho Yoshioka、Ayako Tonoki、Motoyuki Itoh
    • Organizer
      第14回 次世代を担う若手ファーマ・バイオフォーラム2015
    • Place of Presentation
      千葉大学亥鼻キャンパス
    • Year and Date
      2015-09-12
    • Related Report
      2015 Annual Research Report
  • [Presentation] Mib1 controls cell migration via negative regulation of Ctnnd1 activity.2015

    • Author(s)
      Takamasa Mizoguchi, Kazuya Hirose, Shoko Ikeda, Saori Watanabe, Sasa Yang, Motoyuki Itoh.
    • Organizer
      第48回日本発生生物学会大会
    • Place of Presentation
      つくば国際会議場
    • Year and Date
      2015-06-03
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Mib2ノックアウトゼブラフィッシュは明暗周期誘発行動が抑制される2014

    • Author(s)
      中浦 水輝、川原 敦雄、伊藤 素行
    • Organizer
      第58回日本薬学会関東支部大会
    • Place of Presentation
      昭和薬科大学 キャンパス
    • Year and Date
      2014-10-04
    • Related Report
      2014 Annual Research Report
  • [Presentation] DeltaA plays a role in exploratory behavior2014

    • Author(s)
      Miki Chin, Motoyuki Itoh
    • Organizer
      第20回小型魚類研究会
    • Place of Presentation
      慶應義塾大学薬学部(芝共立キャンパス)
    • Year and Date
      2014-09-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] The appropriate control of the Notch signaling activity is required for various neuronal subtype differentiation and their functions2014

    • Author(s)
      Takamasa Mizoguchi, Mizuki Nakaura, Michi Fukada, Miki Chin, Koichi Kawakami, Motoyuki Itoh
    • Organizer
      第20回小型魚類研究会
    • Place of Presentation
      慶應義塾大学薬学部(芝共立キャンパス)
    • Year and Date
      2014-09-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] Different combinations of Notch ligands and receptors regulate V2 interneuron progenitor proliferation and V2a /V2b cell fate determination.2014

    • Author(s)
      Sayumi Okigawa, Takamasa Mizoguchi, Makoto Okanao, Haruna Tanaka, Miho Isoda, Yun-Jin Jiang, Maximiliano Susuter, Shinichi Higashijima, Koichi Kawakami, Motoyuki Itoh
    • Organizer
      第47回日本発生生物学会大会
    • Place of Presentation
      WINC AICHI 名古屋
    • Year and Date
      2014-05-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] Target gene knockdown by 2’, 4’-BNA/LNA antisense oligonucleotides in zebrafish,2014

    • Author(s)
      Mizuki Nakaura, Takeshi Imanishi, Satoshi Obika, Motoyuki Itoh
    • Organizer
      第47回日本発生生物学会大会
    • Place of Presentation
      WINC AICHI 名古屋
    • Year and Date
      2014-05-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] Mib1 regulates cell migration via ubiquitination of p120ctn2013

    • Author(s)
      Takamasa Mizoguchi, Kazuya Hirose, Shoko Ikeda, Saori Watanabe, Motoyuki Itoh
    • Organizer
      第46回日本発生生物学会大会
    • Place of Presentation
      くにびきメッセ 島根県松江市
    • Related Report
      2013 Annual Research Report
  • [Presentation] Notchシグナル:細胞の分化・増殖からがん化2013

    • Author(s)
      伊藤素行
    • Organizer
      第40 回日本毒性学会学術年会
    • Place of Presentation
      幕張メッセ 国際会議場 千葉県千葉市
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Mib1 is involved in the migration of the posterior lateral line primordium via Notch independent pathway.2012

    • Author(s)
      Takamasa Mizoguchi, Kazuya Hirose, Motoyuki Itoh
    • Organizer
      The 10th International Conference on Zebrafish Development and Genetics
    • Place of Presentation
      Madison, WI. USA
    • Year and Date
      2012-06-22
    • Related Report
      2012 Annual Research Report
  • [Remarks] 生化学研究室ホームページ

    • URL

      http://www.p.chiba-u.ac.jp/lab/seika/index.html

    • Related Report
      2013 Annual Research Report
  • [Remarks]

    • URL

      http://www.p.chiba-u.ac.jp/lab/seika/index.html

    • Related Report
      2012 Annual Research Report

URL: 

Published: 2012-04-24   Modified: 2019-07-29  

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