Mechanical control of gene expression and its biological siginificance

• Project/Area Number: 24370085
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Developmental biology
• Research Institution: Tohoku University
• Principal Investigator: OGURA Toshihiko 東北大学, 加齢医学研究所, 教授 (60273851)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000); Fiscal Year 2014: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2013: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2012: ¥11,050,000 (Direct Cost: ¥8,500,000、Indirect Cost: ¥2,550,000)
• Keywords: 細胞力覚 / 遺伝子発現 / 力刺激 / 細胞質／核移行 / MKL2 / Hippo / メカノトランスダクション / 遺伝子破棄 / 力覚分子 / 遺伝子破壊

Outline of Final Research Achievements

As observed as severe muscular atrophy of astronauts in micro-gravity situation, a loss of mechanical stimuli causes failure of homeostasis maintenance. However, molecular mechanisms by which cells and tissues sense physical force stimuli are largely unknown. In this research, we have identified several force-sensitive factors that control gene expression in living tissues. By extensive analyses, we now know that these factors play essential roles in cardiac development, maintenance of circulatory homeostasis, energy metabolism wound healing/regeneration. Our data provide fundamental insights into the disuse syndrome of astronauts and bedridden old patients, obesity/diabetes and their therapeutic approaches.

Research Products

• [Journal Article] New BRAF knockin mice provide a pathogenetic mechanism of developmental defects and a therapeutic approach in cardio-facio-cutaneous syndrome. (2014)
  • Author(s): Inoue S. I. et al.
  • Journal Title: Hum. Mol. Genet. Volume: 23 Issue: 24 Pages: 6553-6566
  • DOI: 10.1093/hmg/ddu376
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Introducing Micrometer-Sized Artificial Objects into Live Cells: A Method for Cell-Giant Unilamellar Vesicle Electrofusion. (2014)
  • Author(s): Sato A. C. et al.
  • Journal Title: PLoS ONE Volume: 9 Issue: 9 Pages: e106853-e106853
  • DOI: 10.1371/journal.pone.0106853
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Reconstruction and in vivo analysis of the extinct tbx5 gene from ancient wingless moa (Aves: Dinornithiformes) (2014)
  • Author(s): Huynen L. et al.
  • Journal Title: BMC Evolutionary Biology Volume: 14 Issue: 1 Pages: 75-82
  • DOI: 10.1186/1471-2148-14-75
  • Peer Reviewed / Open Access
• [Journal Article] Gain-of-Function Mutations in RIT1 Cause Noonan Syndrome, a RAS/MAPK Pathway Syndrome (2013)
  • Author(s): Aoki Y, Niihori T, Banio T, Okamoto N, Mizuno S, Kurosawa K, Ogata T, Takada F, Yano M, Ando T, Hoshika T, Barnett C, Ohashi H, Kawame H, Hasegawa T, Okutani T, Nagashima T, Hasegawa S, Funayama R, Nagashima T Nakayama K, Inoue S, Watanabe Y, Oeura T, Matsubara Y
  • Journal Title: The American Journal of Human Genetics Volume: Volume 93, Issue 1 Issue: 1 Pages: 173-180
  • DOI: 10.1016/j.ajhg.2013.05.021
  • Peer Reviewed
• [Journal Article] Haemodynamically dependent valvulogenesis of zebrafish heart is mediated by flow-dependent expression of miR-21 (2013)
  • Author(s): Banjo T, Grajcarek J, Yoshino D, Osada H, Miyasaka KY, Kida YS, Ueki Y, Nagayama K Kawakami K, Matsumoto T, Sato M, Ogura T
  • Journal Title: Nature Communications Volume: 4,1978 Issue: 1 Pages: 1978-1978
  • DOI: 10.1038/ncomms2978
  • Peer Reviewed / Open Access
• [Presentation] Hemodynamic Forces as a Regulator of Cardiogenesis and Circulatory Homeostasis (2014)
  • Author(s): 小椋利彦
  • Organizer: The 62nd NIBB conference
  • Place of Presentation: Okazaki, JAPAN
  • Year and Date: 2014-11-17 – 2014-11-19
  • Invited
• [Presentation] 力を視点に、生命現象を再解釈する (2013)
  • Author(s): 小椋利彦
  • Organizer: 第19回創発システムシンポジウム（創発夏の学校2013）チュートリアル講演＆ワークショップ
  • Place of Presentation: 大阪
  • Invited
• [Presentation] 生命現象を力学的に再解釈する、そして、生命現象を再構築する
  • Author(s): 小椋利彦
  • Organizer: 東京工業大学生体システム専攻バイオサイエンスシンポジウム
  • Place of Presentation: 東京
  • Invited
• [Presentation] 生命現象を力を視点に再解釈するために
  • Author(s): 小椋利彦
  • Organizer: 生物物理学会東北支部会
  • Place of Presentation: 仙台
  • Invited
• [Presentation] 細胞は力をどのように感知し、どのように反応するか
  • Author(s): 小椋利彦
  • Organizer: 日本人類遺伝学会第８回大会特別講演
  • Place of Presentation: 仙台
  • Invited
• [Presentation] Physical forces as a regulator of morphogenesis and homeostasis; paving a way to medical application
  • Author(s): 小椋利彦
  • Organizer: 第8回研究所ネットワーク国際シンポジウム
  • Place of Presentation: 京都
  • Invited
• [Book] 細胞工学 (2014)
  • Author(s): 小椋利彦（監修）
  • Total Pages: 53
  • Publisher: 秀潤社