Movement and function of secreted signaling proteins in the extracellular environment

• Project/Area Number: 17082012
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: National Institutes of Natural Sciences Okazaki Research Facilities
• Principal Investigator: TAKADA Shinji National Institutes of Natural Sciences Okazaki Research Facilities, 岡崎統合バイオサイエンスセンター, 教授 (60206753)
• Co-Investigator(Kenkyū-buntansha): KOSHIDA Sumito 基礎生物学研究所, 分子発生学研究部門, 准教授 (40342638) ; AKANUMA Takashi 大学共同利用機関法人自然科学研究機構(岡崎共通研究施設), 岡崎統合バイオサイエンスセンター, 特別協力研究員 (50450721)
• Co-Investigator(Renkei-kenkyūsha): TAKADA Ritsuko 大学共同利用機関法人自然科学研究機構(岡崎共通研究施設), 岡崎統合バイオサイエンスセンター, 特別協力研究員 (40450720) ; CHEN Quihong 大学共同利用機関法人自然科学研究機構(岡崎共通研究施設), 岡崎統合バイオサイエンスセンター, 特別協力研究員 ; YABE Taijiro 大学共同利用機関法人自然科学研究機構(岡崎共通研究施設), 岡崎統合バイオサイエンスセンター, 特別協力研究員 (30470074)
• Project Period (FY): 2005 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥104,100,000 (Direct Cost: ¥104,100,000); Fiscal Year 2009: ¥19,500,000 (Direct Cost: ¥19,500,000); Fiscal Year 2008: ¥19,500,000 (Direct Cost: ¥19,500,000); Fiscal Year 2007: ¥20,400,000 (Direct Cost: ¥20,400,000); Fiscal Year 2006: ¥20,400,000 (Direct Cost: ¥20,400,000); Fiscal Year 2005: ¥24,300,000 (Direct Cost: ¥24,300,000)
• Keywords: 発生・分化 / 遺伝子 / シグナル伝達 / 発生 / 脊椎動物 / 脂質修飾 / 翻訳後修飾 / 体節 / 細胞外環境

Research Abstract

動物の発生や恒常性の維持には、分泌性シグナルタンパク質は重要な働きをする。シグナルタンパク質により制御される現象が秩序正しく起きるためには、シグナルタンパク質の分泌と細胞外での拡散が精密にコントロールされる必要がある。本研究では、代表的なシグナルタンパク質であるWntに着目し、その分泌の関わる脂肪酸修飾機構について詳細に明らかにするとともに、経時的観察等によりWntの拡散の様子を明らかにした。

Research Products

• [Journal Article] Planar polarization of node cells determines the rotational axis of node cilia. (2010)
  • Author(s): Hashimoto, H, 他(11人中8番目)
  • Journal Title: Nat Cell Biol. 12 Pages: 170-176
  • Peer Reviewed
• [Journal Article] A novel regulatory mechanism for Fgfl8 signaling involving cysteine-rich FGF receptor (Cfr) and delta-like protein (Dlk) (2010)
  • Author(s): Miyaokal, Y., 他(5名中4番目)
  • Journal Title: Development 137 Pages: 159-167
  • Peer Reviewed
• [Journal Article] Modulation of Wnt signaling by the nucleaz localization of cellulaz FLIP-L (2010)
  • Author(s): Katayama R, 他(7名中3番目)
  • Journal Title: J.Cell Sci. 123 Pages: 23-28
  • Peer Reviewed
• [Journal Article] Motor neurons with axial muscle projections specified by Wnt4/5 signaling. (2009)
  • Author(s): Agalliu D, Takada S, Agalliu I, McMahon AP, Jessell TM
  • Journal Title: Neuron 61 Pages: 708-720
  • Peer Reviewed
• [Journal Article] Motor neurons with axial muscle projections specified by Wnt4/5 signaling. (2009)
  • Author(s): Agalliu D, Takada S, Agalliu I, McMahon AP, Jessell TM.
  • Journal Title: Neuron 61 Pages: 708-720
  • Peer Reviewed
• [Journal Article] Wnt canonical pathway restricts graded Shh/Gli patterning activity through the regulation of Gli3 expression (2008)
  • Author(s): Alvarez-Medina, R., Cayuso, J., Okubo, T., Takada, S., Marti, E.
  • Journal Title: Development 135 Pages: 237-247
  • Peer Reviewed
• [Journal Article] Activator-to-repressor conversion of T-box transcription factors by the Ripply family of Groucho/TLE-associated mediators. (2008)
  • Author(s): Kawamura, A., Koshida, S., & Takada, S.
  • Journal Title: Mol Cell Biol. 28 Pages: 3236-3244
  • Peer Reviewed
• [Journal Article] Stabilized {beta}-Catenin Functions through TCF/LEF Proteins and the Notch/RBP-J{kappa} Complex To Promote Proliferation and Suppress Differentiation of Neural Precursor Cells. (2008)
  • Author(s): Shimizu T, Kagawa T, Inoue T, Nonaka A, Takada S, Aburatani H, & Taga T.
  • Journal Title: Mol Cell Biol. 28 Pages: 7427-7441
  • Peer Reviewed
• [Journal Article] Wnt canonical pathway restricts graded Shh/Gli patterning activity throngh the regulation of Gli3 expression (2008)
  • Author(s): Alvarez-Medina, R., Cayuso, J., Okubo, T., Takada, S., &Marti, E
  • Journal Title: Development 135 Pages: 237-247
  • Peer Reviewed
• [Journal Article] Paf1 complex homologes are required for Notch-regulated transcription during somite segmentation. (2007)
  • Author(s): Akanuma, T., Koshida, S., Kawamura, A., Kishimoto, Y., Takada, S.
  • Journal Title: EMBO Rep 8 Pages: 858-863
  • Peer Reviewed
• [Journal Article] Pafl complex homologes are required for Notch-regulated transcription during somite segmentation (2007)
  • Author(s): Akanuma, T., Koshida, S., Kawamura, A., Kishimoto, Y., &Takada. S.
  • Journal Title: EMBO Rep 8 Pages: 858-863
  • Peer Reviewed
• [Journal Article] A histone lysine methyltransferase activated by non-canonica lWnt signalling suppresses PPAR-gamma transactivation (2007)
  • Author(s): Takada, I. 他 19人中15番目
  • Journal Title: Nat.Cell Biol. 9 Pages: 1273-1285
  • Peer Reviewed
• [Journal Article] Impairment of the ubiquitin-proteasome system by cellular FLIP (2007)
  • Author(s): Ishioka, T. 他 10人中5番目
  • Journal Title: Genes Cells 12 Pages: 735-744
  • Peer Reviewed
• [Journal Article] Monounsaturated fatty acid modification of Wnt proteins: Its role in Wnt secretion. (2006)
  • Author(s): Takada, R., Satomi, Y., Kurata, T., Ueno, N., Norioka, S., Kondoh, H., Takao, T., Takada, S.
  • Journal Title: Dev. Cell 11 Pages: 791-801
  • Peer Reviewed
• [Journal Article] Grainyhead-related transcription factor is required for duct maturation in the salivary gland and the kidney of the mouse. (2006)
  • Author(s): Yamaguchi Y,., Yonemura, S., Takada, S.
  • Journal Title: Development 133 Pages: 4737-4748
  • Peer Reviewed
• [Journal Article] Monounsaturated fatty acid modification of Wnt proteins : Its role in Wnt secretion. (2006)
  • Author(s): Takada, R., Satomi, Y., Kurata, T., Ueno, N., Norioka, S., Kondoh, H., Takao, T., Takada, S.
  • Journal Title: Dev. Cell 11 Pages: 791-801
• [Journal Article] Filopodia formation mediated by receptor tyrosine kinase Ror2 is required for Wnt5a-induced cell migration (2006)
  • Author(s): Nishita, M., Yoo, S.K., Nomachi, A., Kani, S., Sougawa, N., Ohta, Y., Takada, S., Kikuchi, A., Minami, Y.
  • Journal Title: J. Cell Biol. 175 Pages: 552-562
• [Journal Article] Wilms' tumor 1-associating protein regulates G2/M transition through stabilization of cyclin A2 mRNA. (2006)
  • Author(s): Horiuchi, K., Umetani, M., Minami, T., Okayama, H., Takada, S., Yamamoto, M., Aburatani, H., Reid, P.C., Housman, D.E., Hamakubo, T., Kodama, T.
  • Journal Title: Proc Natl Acad Sci U S A. 103 Pages: 17278-17283
• [Journal Article] Grainyhead-related transcription factor is required for duct maturation in the salivary gland and the kidney of the mouse. (2006)
  • Author(s): Yamaguchi Y., Yonemura, S., Takada, S.
  • Journal Title: Development 133 Pages: 4737-4748
• [Journal Article] Determinative role of Wnt signals in dorsal iris-derived lens regeneration in newt eye. (2006)
  • Author(s): Hayashi, T., Mizuno, N., Takada, R., Takada, S., Kondoh, H.
  • Journal Title: Mech Dev. 123 Pages: 793-800
• [Journal Article] Activation of canonical Wnt pathway promotes proliferation of retinal stem cells derived from adult mouse ciliary margin. (2006)
  • Author(s): Inoue T, Kagawa T, Fukushima M, Shimizu T, Yoshinaga Y, Takada S, Tanihara H, Taga T
  • Journal Title: Stem Cells. 24 Pages: 95-104
• [Journal Article] Analysis of combinatorial effects of Wnts and Frizzleds on b-catenin/armadillo stabilization and Dishevelled phosphorylation. (2005)
  • Author(s): Takada, R., Hijikata, H., Kondoh, H, Takada, S.
  • Journal Title: Genes Cells 10 Pages: 919-928
  • Peer Reviewed
• [Journal Article] Zebrafish Hairy/Enhancer of split protein links FGF signaling to cyclic gene expression in the periodic segmentation of somites. (2005)
  • Author(s): Kawamura, A., Koshida, S., Hijikata, H., Sakaguchi, T., Kondoh, H., Takada, S.
  • Journal Title: Genes Dev. 19 Pages: 1156-1161
  • Peer Reviewed
• [Journal Article] Groucho-associated transcriptional repressor Ripply1 is required for proper transition from the presomitic mesoderm to somites. (2005)
  • Author(s): Kawamura, A., Koshida, S., Hijikata, H., Ohbayashi, A., Kondoh, H., Takada, S.
  • Journal Title: Developmental Cell 9 Pages: 735-744
• [Journal Article] Analysis of combinatorial effects of Wnts and Frizzleds on β-catenin/armadillo stabilization and Dishevelled phosphorylation. (2005)
  • Author(s): Takada, R., Hijikata, H., Kondoh, H., Takada, S.
  • Journal Title: Genes to Cells 10 Pages: 919-928
• [Journal Article] Zebrafish Hairy/Enhancer of split protein links FGF signaling to cyclic gene expression in the periodic segmentation of somites. (2005)
  • Author(s): Kawamura, A., Koshida, S., Hijikata, H., Sakaguchi, T., Kondoh, H., Takada, S.
  • Journal Title: Genes & Development 19 Pages: 1156-1161
• [Journal Article] Integrinα5-dependent Fibronectin Accumulation for Maintenance of Somite Boundaries in Zebrafish Embryos (2005)
  • Author(s): Koshida S, Kishimoto Y, Ustumi H, Shimizu T, Furutani-Seiki M, Kondoh H, Takada S
  • Journal Title: Developmental Cell 8 Pages: 587-598
• [Journal Article] Gene trap screening as an effective approach for identification of Wnt-responsive genes in the mouse embryo. (2005)
  • Author(s): Yamaguchi Y, Ogura S, Ishida M, Karasawa M, Takada S.
  • Journal Title: Developmental Dynamics 233 Pages: 484-495
• [Journal Article] Regulation of mammalian tooth cusp patterning by ectodin. (2005)
  • Author(s): Kassai, Y, 他(10名中7番目)
  • Journal Title: Science 309 Pages: 2067-2070
• [Journal Article] Analysis of Ripply 1/2-deficient mouse embryos reveals a mechanism underlying the rostro-caudal patterning within a somite.
  • Author(s): Takahashi J., 他(7名中7番目)
  • Journal Title: Dev.Biol. (印刷中)
  • Peer Reviewed
• [Presentation] 細胞外環境におけるWntタンパク質の時空間的動態の解析 (2010)
  • Author(s): 中山啓, 高田慎治
  • Organizer: 定量生物の会 第2回年会
  • Place of Presentation: 大阪府 大阪大学
• [Presentation] Roles of Porcupine in Zebrafish Development (2009)
  • Author(s): Chen Q. Takada S.
  • Organizer: 2009 Wnt Meeting
  • Place of Presentation: Washington DC (USA)
  • Year and Date: 2009-06-12
• [Presentation] Roles of Porcupine in Zebrafish Development (2009)
  • Author(s): 陳秋紅, 高田慎治
  • Organizer: WNT 2009 meeting
  • Place of Presentation: ジョージタウン大学Washington D.C.,米国
• [Presentation] Specific lipidation and structure of secreted Wnt proteins (2008)
  • Author(s): Takada S
  • Organizer: OIST symposium on Gradient and Signalling: from chemotaxis to development
  • Place of Presentation: 沖縄
  • Year and Date: 2008-11-19
• [Presentation] Specific lipidation and structure of secreted Wnt proteins (2008)
  • Author(s): Shinji Takada
  • Organizer: OIST symposium on Gradient and Signalling
  • Place of Presentation: 沖縄
  • Year and Date: 2008-11-19
• [Presentation] Roles of Wntless in zebrafish development (2008)
  • Author(s): Qiuhong Chen, Shinji Takada
  • Organizer: 第41回日本発生生物学会大会
  • Place of Presentation: 徳島
• [Presentation] Wnt proteins, modified with mono-unsaturated fatty acids, are secreted as self-assembled oligomers from cultured cells (2008)
  • Author(s): Ritsuko Takada, Shinji Takada
  • Organizer: 第60回日本細胞生物学会大会
  • Place of Presentation: 横浜
• [Presentation] Wnt protein requires an unexpected type of lipid modification for its secretion. (2007)
  • Author(s): Takada S
  • Organizer: 日本発生生物学会、日本細胞生物学会合同年会
  • Place of Presentation: 福岡
  • Year and Date: 2007-05-30
• [Presentation] Wnt protein requires an unexpected type of lipid modification for its secretion (2007)
  • Author(s): Takada S.
  • Organizer: 第40回日本発生生物学会, 第59回目本細胞生物学会合同年会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2007-05-29
• [Presentation] Wnt protein require lipid modification for its secretion (2007)
  • Author(s): Takada S.
  • Organizer: Korea-Japan Joint Meetillg on Cellular Sigpaling and Molecular Imaging
  • Place of Presentation: Seoul
  • Year and Date: 2007-02-22
• [Presentation] Wnt proteins are secreted as high-molecular-weight complexes fom cultured cells (2007)
  • Author(s): Takada R. & Takada S.
  • Organizer: Wnt signaling in Development and Disease
  • Place of Presentation: Berlin
• [Presentation] Unsaturated Fatty Acid Modification is Requiredd for Wnt Secretio (2007)
  • Author(s): Takada S.
  • Organizer: The 5th NIBB-EMBL Symposium on Cell and Developmental Biologyn
  • Place of Presentation: 岡崎コンファレンスセンタ
• [Presentation] Wntタンパク質の脂質修飾、分泌、細胞外輸送 (2006)
  • Author(s): 高田慎治
  • Organizer: 日本分子生物学会2006フォーラム
  • Place of Presentation: 名古屋
  • Year and Date: 2006-12-06
• [Remarks] 新聞発表
• [Remarks] (1)Wntタンパク質の脂肪酸修飾に関する成果」日経産業新聞2006年12月6日掲載、科学新聞2006年12月15日掲載
• [Remarks] (2)「Wntタンパク質の発生過程における機能の解析に関する成果」日経産業新聞2006年11月9日掲載
• [Remarks] ホームページ
  • URL: http://www.nibb.ac.jp/cib2/
• [Remarks]
  • URL: http://www.nibb.ac.jp/cib2/
• [Remarks]
  • URL: http://www.nibb.ac.jp/cib2/