Signal transduction networks regulating life span and development

• Project/Area Number: 26221101
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Functional biochemistry
• Research Institution: Institute of Physical and Chemical Research (2018); Kyoto University (2014-2017)
• Principal Investigator: Nishida Eisuke 国立研究開発法人理化学研究所, 生命機能科学研究センター, センター長 (60143369)
• Project Period (FY): 2014-05-30 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥195,000,000 (Direct Cost: ¥150,000,000、Indirect Cost: ¥45,000,000); Fiscal Year 2018: ¥39,000,000 (Direct Cost: ¥30,000,000、Indirect Cost: ¥9,000,000); Fiscal Year 2017: ¥39,000,000 (Direct Cost: ¥30,000,000、Indirect Cost: ¥9,000,000); Fiscal Year 2016: ¥39,000,000 (Direct Cost: ¥30,000,000、Indirect Cost: ¥9,000,000); Fiscal Year 2015: ¥39,000,000 (Direct Cost: ¥30,000,000、Indirect Cost: ¥9,000,000); Fiscal Year 2014: ¥39,000,000 (Direct Cost: ¥30,000,000、Indirect Cost: ¥9,000,000)
• Keywords: 寿命 / 発生 / シグナル伝達 / 老化 / 細胞情報伝達 / 細胞情報伝達機構

Outline of Final Research Achievements

Using C. elegans, we identified molecular mechanisms underlying the transgenerational inheritance of acquired traits such as stress-induced longevity. We also identified several signaling pathways regulating diet restriction-induced longevity. Moreover, using Xenopus embryos, we identified signaling pathways regulating ciliated cell differentiation. Also, we developed a novel method for in vivo gene delivery into intestines of living mice, and found that the Hippo pathway regulates both stem cell proliferation and goblet cell differentiation in intestine epithelia.

Academic Significance and Societal Importance of the Research Achievements

外因性ストレスによる寿命延長等の獲得形質の次世代への継承は、線虫のみならず動物一般の生存戦略のひとつである可能性が考えられ、そのメカニズムの解明は意義深い。また、ヒト生理機能にも必須となる繊毛細胞の発生に関与する、一連のシグナル伝達経路を明らかにすることができた。さらに、我々が開発したマウス腸上皮に遺伝子を導入する方法は、スイス連邦工科大学ローザンヌ校との共同研究に発展するなど、国際的な注目を集めた。

Assessment Rating

Result (Rating)

A: Progress in the research is steadily towards the initial goal. Expected research results are expected.

Research Products

• [Journal Article] The atypical mitogen-activated protein kinase ERK3 is essential for establishment of epithelial architecture (2018)
  • Author(s): Chika Takahashi, Koichi Miyatake, Morioh Kusakabe, Eisuke Nishida
  • Journal Title: Journal of Biological Chemistry Volume: 293 Pages: 8342-8361
  • DOI: 10.1074/jbc.ra117.000992
  • Peer Reviewed
• [Journal Article] Molecular mechanisms regulating lifespan and environmental stress responses (2018)
  • Author(s): Saya Kishimoto, Masaharu Uno, Eisuke Nishida
  • Journal Title: Inflammation and Regeneration Volume: 38 Pages: 1-7
  • DOI: 10.1186/s41232-018-0080-y
  • Peer Reviewed
• [Journal Article] The MYST family histone acetyltransferase complex regulates stress resistance and longevity through transcriptional control of DAF‐16/FOXO transcription factors (2017)
  • Author(s): Ikeda Takako、Uno Masaharu、Honjoh Sakiko、Nishida Eisuke
  • Journal Title: EMBO reports Volume: 18 Pages: 1716-1726
  • DOI: 10.15252/embr.201743907
  • Peer Reviewed
• [Journal Article] The microRNA machinery regulates fasting-induced changes in gene expression and longevity inCaenorhabditis elegans (2017)
  • Author(s): Kogure Akiko、Uno Masaharu、Ikeda Takako、Nishida Eisuke
  • Journal Title: Journal of Biological Chemistry Volume: 292 Pages: 11300-11309
  • DOI: 10.1074/jbc.m116.765065
  • Peer Reviewed
• [Journal Article] Octopamine enhances oxidative stress resistance through the fasting-responsive transcription factor DAF-16/FOXO in C. elegans. (2017)
  • Author(s): Hoshikawa H. et al.
  • Journal Title: Genes to Cells Volume: 22 Pages: 210-219
  • DOI: 10.1111/gtc.12469
  • Peer Reviewed
• [Journal Article] Environmental stresses induce transgenerationally inheritable survival advantages via germline-tosoma communication in Caenorhabditis elegans (2017)
  • Author(s): Kishimoto S. et al.
  • Journal Title: Nature Communications Volume: 8 Pages: 14031-14031
  • DOI: 10.1038/ncomms14031
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Cholesterol regulates DAF-16 nuclear localization and fasting-induced longevity in C. elegans (2017)
  • Author(s): Ihara A. et al.
  • Journal Title: Exp Gerontol. Volume: 87 Pages: 40-47
  • DOI: 10.1016/j.exger.2016.10.011
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] mab21-l3 regulates cell fate specification of multiciliate cells and ionocytes. (2015)
  • Author(s): Chika Takahashi, Morioh Kusakabe, Toshiyasu Suzuki, Koichi Miyatake and Eisuke Nishida
  • Journal Title: Nature Commun. Volume: 6 (6017) Pages: 1-13
  • DOI: 10.1038/ncomms7017
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] ERK7 regulates ciliogenesis by phosphorylating the actin regulator CapZIP in cooperation with Dishevelled. (2015)
  • Author(s): Miyatake K. et al.
  • Journal Title: Nature Communications Volume: 6 Pages: 1-12
  • DOI: 10.1038/ncomms7666
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Small RNAs are required for the transgenerational inheritance of the acquired stress resistance. (2018)
  • Author(s): Emiko Okabe, Saya Kishimoto, Masaharu Uno, Eisuke Nishida
  • Organizer: The 2018 C. elegans "Topics" Meeting
  • Int'l Joint Research
• [Presentation] ERK3 regulates the integrity of epithelia (2017)
  • Author(s): Takahashi et al.
  • Organizer: 18th International Congress of Developmental Biology
  • Int'l Joint Research
• [Presentation] Environmental stresses induce transgenerationally inheritable survival advantages via germline-to-soma sommunication in C. elegans (2017)
  • Author(s): Kishimoto et al.
  • Organizer: 21st International C. elegans Conference
  • Int'l Joint Research
• [Presentation] Environmental stresses induce transgenerationally inheritable survival advantages via germline-to-soma communications (2016)
  • Author(s): Saya Kishimoto, Masaharu Uno, and Eisuke Nishida
  • Organizer: C. elegans Development, Cell Biology and Gene Expression Meeting
  • Place of Presentation: The Orlando World Center Marriott, Orlando, Florida, USA
  • Year and Date: 2016-07-14
  • Int'l Joint Research
• [Presentation] Role of nuclear Argonaute proteins in the inheritance of acquired stress resistance in C. elegans (2016)
  • Author(s): Emiko Okabe, Saya Kishimoto, Masaharu Uno, Eisuke Nishida
  • Organizer: C. elegans Development, Cell Biology and Gene Expression Meeting
  • Place of Presentation: The Orlando World Center Marriott, Orlando, Florida, America
  • Year and Date: 2016-07-13
  • Int'l Joint Research
• [Presentation] 線虫におけるヒストンH3K4トリメチル化修飾因子による寿命制御メカニズムの解析 (2016)
  • Author(s): 農野将功、宇野雅晴、西田栄介
  • Organizer: 第68回日本細胞生物学会大会
  • Place of Presentation: 京都テルサ・京都・日本
• [Presentation] A Notch-repressed gene mab21-l3 is a key regulator for cell fate specification of multiciliate cells and ionocytes (2015)
  • Author(s): Morioh Kusakabe, Chika Takahashi, and Eisuke Nishida
  • Organizer: BMB2015
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2015-12-02
  • Invited
• [Presentation] Transgenerational inheritance of hormetic effects in C. elegans (2015)
  • Author(s): Saya Kishimoto, Masaharu Uno, and Eisuke Nishida
  • Organizer: 20th International C. elegans Meeting
  • Place of Presentation: Univ. of California, LA, USA
  • Year and Date: 2015-06-25
  • Int'l Joint Research
• [Presentation] Effects of paraquat treatment on life span in C. elegans (2015)
  • Author(s): Masaharu Uno and Eisuke Nishida
  • Organizer: EMBO workshop, Developmental circuits in aging
  • Place of Presentation: Aldemar Knossos Royal, Heraklion, Greek
  • Year and Date: 2015-05-26
  • Int'l Joint Research
• [Presentation] Mechanisms of life-span regulation by environmental stresses in C. elegans. (2014)
  • Author(s): Masaharu Uno, Eisuke Nishida
  • Organizer: 第37回分子生物学会年会
  • Place of Presentation: パシフィコ横浜・神奈川・日本
  • Year and Date: 2014-11-25
  • Invited
• [Presentation] Xenopus mab21-l3 is required for cell fate specification of multiciliate (2014)
  • Author(s): Chika Takahashi, Morioh Kusakabe, Toshiyasu Suzuki, Koichi Miyatake and Eisuke Nishida
  • Organizer: 15th International Xenopus Conference
  • Place of Presentation: Asilomar Conference Grounds, Pacific Grove, California, USA
  • Year and Date: 2014-08-24 – 2014-08-28
• [Presentation] ERK7, a novel regulator of ciliogenesis, is required for basal body migration (2014)
  • Author(s): Koichi Miyatake, Morioh Kusakabe, Chika Takahashi, Eisuke Nishida
  • Organizer: 15th International Xenopus Conference
  • Place of Presentation: Pacific Grove, California, USA
  • Year and Date: 2014-08-24 – 2014-08-28