Fgf8 signaling for cerebellar differentiation

• Project/Area Number: 19370090
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Developmental biology
• Research Institution: Tohoku University
• Principal Investigator: NAKAMURA Harukazu Tohoku University, 大学院・生命科学研究科, 教授 (90079690)
• Research Collaborator: SUZUKI-HIRANO Asuka 東北大学, 大学院・生命科学研究科, PD ; HARADA Hidekiyo 東北大学, 大学院・生命科学研究科, 博士課程後期学生
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000); Fiscal Year 2008: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000); Fiscal Year 2007: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
• Keywords: 形態形成 / 細胞内・細胞間情報伝達 / 中脳後脳境界部 / 中脳視蓋 / 小脳 / Fgf8 / Ras-ERK / Sprouty2 / エレクトロポレーション / オーガナイザー / Fgf8-Ras-ERK / シグナルトラレスダクション / Sprouty 2 / 視蓋 / 分化 / ニワトリ胚

Research Abstract

峡部オーガナイザーFgf8の強いシグナルにより、Ras-ERK経路が活性化されると小脳が分化することを示したが、その活性はすぐに抑制される必要があり、ずっと活性化されると中脳胞の小脳への分化転換は起こらない。Fgf8bとDN-Sprouty2の強制発現の後、DN-Sprouty2の転写をOffにすると中脳胞は小脳へとその運命を変えた。本研究により、小脳が分化するためには、Fgf8bによりRas-ERK経路が活性化され、その後負の制御因子Sprouty2, Sef, MKP3等により、その活性が抑制されることが必要であることが明らかになった。

Research Products

• [Journal Article] R-spondin2 expression in the apical ectodermal ridge is essential for outgrowth and patterning in mouse limb development (2008)
  • Author(s): Aoki M, Kiyonari H, Nakamura H, Okamoto H
  • Journal Title: Development Growth & Differentiation 50 Pages: 85-95
  • NAID: 10021095550
  • Peer Reviewed
• [Journal Article] Electroporation in avian embryos (2008)
  • Author(s): Funahashi J, Nakamura H
  • Journal Title: Methods Mol Biol 461 Pages: 377-382
  • Peer Reviewed
• [Journal Article] Tracing retinal fiber trajectory with a method of transposon-mediated genomic integration in chick embryo (2008)
  • Author(s): Harada H, Takahashi Y, Kawakami K, Ogura T, Nakamura H
  • Journal Title: Dev Growth Differ 50 Pages: 697-702
  • NAID: 10022020746
  • Peer Reviewed
• [Journal Article] Isthmus organizer for mesencephalon and metencephalon (2008)
  • Author(s): Nakamura H, Sato T, Suzuki-Hirano A
  • Journal Title: Dev Growth Differ 50 Suppl 1
  • NAID: 10024399510
  • Peer Reviewed
• [Journal Article] 峡部オーガナイザーと小脳・視蓋形成 (2008)
  • Author(s): 仲村春和・杉山清佳・鈴木-平野明日香
  • Journal Title: 蛋白質核酸酵素 53 Pages: 373-378
• [Journal Article] Isthmus organizer for mesencephalon and metencephalon (2008)
  • Author(s): Nakamura, H., Sato, T., Suzuki-Hirano, A.
  • Journal Title: Dev. Growth Differ 50
  • NAID: 10024399510
  • Peer Reviewed
• [Journal Article] R-spondin2 expression in the apical ectodermal ridge is essential for outgrowth and patterning in mouse limb development (2008)
  • Author(s): Aoki, M., Kiyonari, H., Nakamura, H., Okamoto, H.
  • Journal Title: Dev Growth Differ 50 Pages: 85-95
  • NAID: 10021095550
  • Peer Reviewed
• [Journal Article] Electroporation as an efficient method of gene transfer (2008)
  • Author(s): Odani, N., Nakamura, H.
  • Journal Title: Dev Growth Differ 50 Pages: 443-448
  • NAID: 10021097110
  • Peer Reviewed
• [Journal Article] Isthmus organizer for mesencephalon and metencephalon. (2008)
  • Author(s): Nakamura, H., Sato, T. & Suzuki-Hirano, A.
  • Journal Title: Dev Growth Differ 50(In press)
  • NAID: 10024399510
  • Peer Reviewed
• [Journal Article] Electroporation as an efficient method of gene transfer. (2008)
  • Author(s): Odani, N. & Nakamura, H.
  • Journal Title: Dev Growth Differ 50(In press)
  • NAID: 10021097110
  • Peer Reviewed
• [Journal Article] R-spondin2 expression in the apical ectodermal ridge is essential for outgrowth and patterning in mouse limb development. (2008)
  • Author(s): Aoki, M., Kiyonari, H., Nakamura, H. & Okamoto, H.
  • Journal Title: Dev Growth Differ 50 Pages: 85-95
  • NAID: 10021095550
  • Peer Reviewed
• [Journal Article] 峡部オーガナイザーと小脳分化制御・視蓋極性形成および網膜視蓋投射形成 (2008)
  • Author(s): 仲村春和、杉山清佳、佐藤達也、鈴木-平野明日香
  • Journal Title: 蛋白質核酸酵素 53 Pages: 373-378
• [Journal Article] Cloning and developmental expression of a chick G-protein-coupled receptor SCGPR1 (2007)
  • Author(s): Odani N, Pfaff SL, Nakamura H, Funahashi J.
  • Journal Title: Gene Exp Pattern 7 Pages: 375-380
  • Peer Reviewed
• [Journal Article] Role of Bone morphogenetic protein 4 in zebrafish semicircular canal development. (2007)
  • Author(s): Omata, Y., Nojima, Y., Nakayama, S., Okamoto, H., Nakamura, H. & Funahashi, J.
  • Journal Title: Dev Growth Differ 49 Pages: 711-719
  • NAID: 10019984157
  • Peer Reviewed
• [Journal Article] Cloning and developmental expression of a chick G-protein-coupled receptor SCGPR1 (2007)
  • Author(s): Odani N, Pfaff SL, Nakamura H, Funahashi J
  • Journal Title: Gene Expr Patterns 7 Pages: 375-380
  • Peer Reviewed
• [Journal Article] 細胞間相互作用を担うシグナル系
  • Author(s): 仲村春和
  • Journal Title: 化学 62 Pages: 23-27
• [Presentation] Pea3/Ets transcription factors for cerebellar differeniation (2008)
  • Author(s): Harada, H., Sato, T., Nakamura, H.
  • Organizer: 41st Annual Meeting for the Japanese Society of Developmental Biologists
  • Place of Presentation: Tokushima, Japan
• [Presentation] Fgf signaling in tectal polarity formation (2008)
  • Author(s): Harada, H., Tanaka, J., Matsuda, Y., Suzuki-Hirano, A., Nakamura, H.
  • Organizer: Gordon Research Conference 2008 Fibroblast Growth Factors in Development & Disease
  • Place of Presentation: Il Ciocco, Italy
• [Presentation] Regulation of ERK phosphorylation for the MHB formation and cerebellar development (2008)
  • Author(s): Suzuki-Hirano, A., Sato, T., Nakamura, H.
  • Organizer: Gordon Research Conference 2008 Fibroblast Growth Factors in Development & Disease
  • Place of Presentation: Il Ciocco, Italy
• [Presentation] Regulation of the Fgf8-Ras-ERK signaling pathway for cerebellar development (2008)
  • Author(s): Nakamura, H.
  • Organizer: GCOE International Zao Conference
  • Place of Presentation: Miyagi, Japan
• [Presentation] Pea3/Ets transcription factors for cerebellar differeniation (2008)
  • Author(s): Harada, H., Sato, T., Nakamura, H.
  • Organizer: 41st Annual Meeting for the Japanese Society of Developmental Biologists
  • Place of Presentation: 徳島市
• [Presentation] Regulation of the Fgf8-Ras-ERK signaling pathway for cerebellar development. (2008)
  • Author(s): Suzuki A., Sato T. & Nakamura, H.
  • Organizer: ZAO Conference, The 1st International Conference of Tohoku Neuroscience GCOE, "from GENES to DEVELOPMENT and BEHAVIOR"
  • Place of Presentation: Zao Royal Hotel, Miyagi, Japan
• [Presentation] Fgf signalingin tectal polarity formation. (2008)
  • Author(s): Harada, H. & Nakamura, H.
  • Organizer: Gordon Conference, Fibroblast Growth Factors in Development & Disease.
  • Place of Presentation: II Ciocco, Italy
• [Presentation] Regulation of ERK phosphorylation for the MHB formation and cerebellar development. (2008)
  • Author(s): Suzuki-Hirano, A. & Nakamura, H.
  • Organizer: Gordon Conference, Fibroblast Growth Factors in Development & Disease.
  • Place of Presentation: II Ciocco, Italy
• [Presentation] Sequential Regulations of ERK signaling activity and cerebellar development (2007)
  • Author(s): Suzuki-Hirano, A, Sato, T.and Nakamura, H
  • Organizer: International chick meeting
  • Place of Presentation: Barcelona
• [Presentation] Analysis of coactosin, an actin binding protein, in neural crest cell migration (2007)
  • Author(s): Hou, X, Katahira,T, Kimura, J, Nakamura, H
  • Organizer: International chick meeting
  • Place of Presentation: Barcelona
• [Presentation] Establishment of anteroposterior axis of the chick optic tectum by Fgf-Ras/ERK signaling (2007)
  • Author(s): Harada, H, Matsuda, Y, Tanaka, J, Suzuki-Hirano, A, Nakamura, H
  • Organizer: International chick meeting
  • Place of Presentation: Barcelona
• [Presentation] Establishment of anteroposterior axis of the chick optic tectum by Fgf-Ras-ERK signaling. (2007)
  • Author(s): Harada, H., Matsuda, Y., Tanaka, J., Suzuki-Hirano, A., & Nakamura, H.
  • Organizer: International Chick Meeting
  • Place of Presentation: Barcelona, Spain
• [Presentation] Analysis of coactosin, an actin binding protein, in neural crest cell migration (2007)
  • Author(s): Hou, X., Katahira, T., Kimura J., & Nakamura, H.
  • Organizer: International Chick Meeting
  • Place of Presentation: Barcelona, Spain
• [Presentation] Sequential regulations of ERK signaling activity and ceebellar development. (2007)
  • Author(s): Suzuki-Hirano, A., Sato, T., & Nakamura, H.
  • Organizer: International Chick Meeting
  • Place of Presentation: Barcelona, Spain
• [Presentation] Role of En2 and Fgf signaling in tectal polarity formation (2007)
  • Author(s): H. HARADA, J. TANAKA, Y. MATUSDA, A. SUZUKI-HIRANO, *H. NAKAMURA
  • Organizer: SFN2007
  • Place of Presentation: San Diego, USA
• [Book] In Ovo Electroporationas a useful tool to pursue molecular mechanisms of neural development in chick embryos. In 'Electroporation and Sonoporation in Developmental Biology' (2009)
  • Author(s): Odani, N., Hou, X., Nakamura, H.
  • Total Pages: 331
  • Publisher: Springer Japan
• [Book] Electroporation and Sonoporation in Developmental Biology(Tokyo) (2008)
  • Author(s): Nakamura, H.(Editor)
  • Total Pages: 331
  • Publisher: Springer Japan
• [Book] Methods in Molecular Biology, Vol 461: Molecular Embryology: Meht-hods and Protocols, 2nd ed(Electroporation as an efficient method of gene transfer) (2008)
  • Author(s): Funahashi, J., Nakamura, H. (eds. P. Sharpe and I. Mason)
  • Publisher: Humana Press, Totowa, NJ.(印刷中)
• [Book] 加齢医学(第VII章 脳はいかにしてかたちづくられるか) (2007)
  • Author(s): 仲村春和(帯刀益夫、佐竹正延編)
  • Total Pages: 300
  • Publisher: 東北大学出版会
• [Book] Encyclopedia of Neuroscience(Regionalization of the vertebrate central nervous system)
  • Author(s): Nakamura, H
  • Publisher: Springer-Verlag(印刷中)
• [Remarks]
  • URL: http://www.lifesci.tohoku.ac.jp/outline/neuro/neuroscience/molecular_neurobiology.html