Analysis of neuronal stem cell-specific expression mechanism of Fgfr3 and its function on corticogenesis

• Project/Area Number: 22500288
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neuroscience in general
• Research Institution: Kyoto University
• Principal Investigator: TAKEUCHI Akihide 京都大学, 医学(系)研究科(研究院), 准教授 (90436618)
• Co-Investigator(Kenkyū-buntansha): HAGIWARA Masatoshi 京都大学, 大学院医学研究科, 教授
• Project Period (FY): 2010-04-01 – 2013-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 神経科学 / 発生・分化 / FGFR3 / 可視化

Research Abstract

Fibroblast growth factor receptor 3 (Fgfr3) is one of the essential molecules during corticogenesis that regulates proliferation and differentiation of neuronal stem cells in mammalian brain. However, its regulatory mechanism is still largely unknown. Here we found that neuronal stem cell-specific expression of Fgr3 is achieved by (1) Fgfr3 promoter activity, and (2) utilizing mutually exclusive alternative splicing regulation of exon 9 and 10. From these analyses in alternative splicing regulators of Fgfr3, we deciphered the mechanism of mammalian corticogenesis.

Research Products

• [Journal Article] CELF family RNA-binding protein UNC-75 regulates two sets of mutually exclusive exons of the unc-32 gene in neuron-specific manners in Caenorhabditis elegans (2013)
  • Author(s): Kuroyanagi H, Watanabe Y, Hagiwara M
  • Journal Title: PLoS Genetics Volume: 9 Issue: 2 Pages: e1003337-e1003337
  • DOI: 10.1371/journal.pgen.1003337
  • Peer Reviewed
• [Journal Article] Muscle-Specific Splicing Factors ASD-2 and SUP-12 Cooperatively Switch Alternative Pre-mRNA Processing Patterns of the ADF/Cofilin Gene in Caenorhabditis elegans (2012)
  • Author(s): Ohno G, Ono K, Togo M, Watanabe Y, Ono S, Hagiwara M, Kuroyanagi H
  • Journal Title: PLoS Genetics Volume: 8 Issue: 10 Pages: e1002991-e1002991
  • DOI: 10.1371/journal.pgen.1002991
  • Peer Reviewed
• [Journal Article] Special Review可視化スプライシング・レポーターシステムで開く (2012)
  • Author(s): 武内章英, 萩原正敏
  • Journal Title: 哺乳類のmRNA制御の世界細胞工学 Volume: Vol.31 No.6 Pages: 698-704
• [Journal Article] Fgfr1 and the IIIc isoform of Fgfr2 play critical roles in the metanephric mesenchyme mediating early inductive events in kidney development (2011)
  • Author(s): Sims-Lucas S, Cusack B, Baust J, Eswarakumar VP, Masatoshi H, Takeuchi A, Bates CM
  • Journal Title: Dev Dyn Volume: 240(1) Issue: 1 Pages: 240-9
  • DOI: 10.1002/dvdy.22501
• [Journal Article] Chemical treatment enhances skipping of a mutated exon in the dystrophin gene (2011)
  • Author(s): Nishida A, Kataoka N, Takeshima Y,Yagi M, Awano, H, Ota, M, Itoh K, Hagiwara M, and Matsuo M
  • Journal Title: Nat Commun Volume: 2 Issue: 1 Pages: 308-308
  • DOI: 10.1038/ncomms1306
  • NAID: 120003001398
  • Peer Reviewed
• [Journal Article] Splicing reporter mice revealed the evolutionally conserved switching mechanism of tissue-specific alternative exon selection (2010)
  • Author(s): Takeuchi A, Hosokawa M, Nojima T, Hagiwara M
  • Journal Title: PLoS One Volume: 5(6) Issue: 6 Pages: e10946-e10946
  • DOI: 10.1371/journal.pone.0010946
• [Presentation] RNA結合タンパク質の機能解析から迫る、哺乳類中枢神経発生におけるRNA制御の意義の解明 (2013)
  • Author(s): 武内章英, 伊藤美佳子, 大野欽司, 萩原正敏
  • Organizer: 第118回日本解剖学会総会・全国学術集会
  • Place of Presentation: サンポートホール香川・かがわ国際会議場
• [Presentation] RNA Binding Protein Sfpq is required for the expression of neuron-specific long pre-mRNAs essential for brain development (2013)
  • Author(s): Akihide Takeuchi, Kei Iida, Kensuke Ninomiya, Mikako Ito, Kinji Ohno, Masatoshi Hagiwara
  • Organizer: The 18th Annual Meeting of the RNA Society Davos
  • Place of Presentation: Switzerland
• [Presentation] RNA結合タンパク質は、mRNA processingを介して脳形成過程で何を制御しているのか? (2013)
  • Author(s): 武内章英, 伊藤美佳子, 大野欽司, 萩原正敏
  • Organizer: Neuro2013
  • Place of Presentation: 国立京都国際会館
• [Presentation] RNA Binding Protein Sfpq is required for the expression of neuron-specific long pre-mRNAs essential for brain development (2013)
  • Author(s): Akihide Takeuchi, Kei Iida, Kensuke Ninomiya, Mikako Ito, Kinji Ohno, Masatoshi Hagiwara
  • Organizer: 2013 CSHL Meeting on Eukaryotic mRNA Processing Cold Spring Harbor Laboratory
  • Place of Presentation: NY, USA
• [Presentation] RNA Binding Protein Sfpq is required for the expression of neuron-specific long pre-mRNAs essential for brain development (2013)
  • Author(s): Akihide Takeuchi, Kei Iida, Kensuke Ninomiya, Mikako Ito, Kinji Ohno, Masatoshi Hagiwara
  • Organizer: Neuroscience 2013 San Diego
  • Place of Presentation: California, USA
• [Presentation] RNA 結合タンパク質の機能解析から迫る、哺乳類中枢神経発生における RNA 制御の意義の解明 (2013)
  • Author(s): 武内 章英、飯田 慶、二宮 賢介、伊藤 美佳子、大野 欽司、萩原 正敏
  • Organizer: 第118回日本解剖学会総会・全国学術集会
  • Place of Presentation: サンポートホール香川・かがわ国際会議場
• [Presentation] RNA Binding Protein Sfpq is required for the expression of neuron-specific long pre-mRNAs essential for brain development. (2013)
  • Author(s): Akihide Takeuchi, Kei Iida, Kensuke Ninomiya, Mikako Ito, Kinji Ohno, Masatoshi Hagiwara
  • Organizer: The 18th Annual Meeting of the RNA Society
  • Place of Presentation: Davos, Switzerland
• [Presentation] What is the function of RNA-binding proteins in the process of brain format ion through regulating mRNA ? (2013)
  • Author(s): 武内 章英、飯田 慶、二宮 賢介、伊藤 美佳子、大野 欽司、萩原 正敏
  • Organizer: Neuro2013
  • Place of Presentation: 国立京都国際会館
• [Presentation] RNA結合タンパク質Sfpqは、神経発生過程において長いpre-mRNAの発現を制御する (2013)
  • Author(s): 武内 章英、飯田 慶、二宮 賢介、伊藤 美佳子、大野 欽司、萩原 正敏
  • Organizer: 第15回日本RNA学会年会
  • Place of Presentation: 愛媛県 県民文化会館・ひめぎんホール
• [Presentation] RNA Binding Protein Sfpq is required for the expression of neuron-specific long pre-mRNAs essential for brain development (2013)
  • Author(s): Akihide Takeuchi, Kei Iida, Kensuke Ninomiya, Mikako Ito, Kinji Ohno, Masatoshi Hagiwara
  • Organizer: 2013 CSHL Meeting on Eukaryotic mRNA Processing
  • Place of Presentation: Cold Spring Harbor Laboratory, NY, USA
• [Presentation] RNA Binding Protein Sfpq is required for the expression of neuron-specific long pre-mRNAs essential for brain development. (2013)
  • Author(s): Akihide Takeuchi, Kei Iida, Kensuke Ninomiya, Mikako Ito, Kinji Ohno, Masatoshi Hagiwara
  • Organizer: Neuroscience 2013
  • Place of Presentation: San Diego, California, USA
• [Presentation] RNA結合タンパク質Quakingの神経特異的ノックアウトマウスの解析 (2013)
  • Author(s): 高橋 裕司、和根崎 圭子、武内 章英、萩原 正敏
  • Organizer: 2013 日本解剖学会近畿地方会
  • Place of Presentation: 奈良先端大学大学院大学
• [Presentation] 哺乳類の脳の発生過程でのmRNA制御の網羅的解析 (2012)
  • Author(s): 武内章英、伊藤美佳子、大野欽司、萩原正敏
  • Organizer: 第117回日本解剖学会総会・全国学術集会
  • Place of Presentation: 山梨大学甲府キャンパス
  • Year and Date: 2012-03-26
• [Presentation] 哺乳類の脳の発生過程でのmRNA制御の網羅的解析 (2012)
  • Author(s): 武内章英, 伊藤美佳子, 大野欽司, 萩原正敏
  • Organizer: 117回日本解剖学会総会
  • Place of Presentation: 全国学術集会山梨大学甲府キャンパス
• [Presentation] 哺乳類の脳の発生過程でのｍＲＮＡ制御の網羅的解析 (2012)
  • Author(s): 武内 章英
  • Organizer: 第117回日本解剖学会総会・全国学術集会
  • Place of Presentation: 山梨県山梨大学甲府キャンパス
• [Presentation] 哺乳類の脳の発生過程でのmRNA制御の網羅的解析Whole-genomic mRNA regulation analysis of neuronal development in mouse brain (2010)
  • Author(s): 武内章英, 渡辺要平, 伊藤美佳子, 大野欽司, 萩原正敏
  • Organizer: BMB2010 (第33回日本分子生物学会年会・第83回日本生化学会大会合同大会)
  • Place of Presentation: 神戸ポートアイランド
• [Remarks]
  • URL: http://www.anat1dadb.med.kyoto-u.ac.jp/
• [Remarks]
  • URL: http://www.anatldadb.med.kyoto-u.ac.jp/Anat1DADB/TOP.html
• [Patent(Industrial Property Rights)] Transgenic reporter system that reveals expression profiles and regulation mechanisms of alternative splicing in mammalian organisms (2013)
  • Inventor(s): Masatoshi Hagiwara, Akihide Takeuchi
  • Industrial Property Rights Holder: Kyoto university
  • Acquisition Date: 2013-01-11
  • Overseas
• [Patent(Industrial Property Rights)] 哺乳類生物における選択的スプライシングの発現プロファイルおよび制御機構を明らかにするトランスジェニックレポーターシステム (2012)
  • Inventor(s): 萩原正敏, 武内章英
  • Industrial Property Rights Holder: 国立大学法人 京都大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2012-554135
  • Filing Date: 2012-11-30
  • Overseas
• [Patent(Industrial Property Rights)] Transgenic reporter system that reveals expression profiles and regulation mechanisms of alternative splicing in mammalian organisms (2012)
  • Inventor(s): Masatoshi Hagiwara, Akihide Takeuchi
  • Industrial Property Rights Holder: Kyoto university
  • Acquisition Date: 2012-11-30
  • Overseas