Analysis for a mechanism of erythroblast migration based on intercellular adhesions

• Project/Area Number: 16K18549
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Developmental biology
• Research Institution: Kyoto University
• Principal Investigator: Iida Atsuo 京都大学, ウイルス・再生医科学研究所, 助教 (90437278)
• Research Collaborator: Wang Zi
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: ゼブラフィッシュ / 血管 / 血球 / インテグリン / 蛍光ライブイメージング / 細胞移動 / 血管内皮細胞 / 赤芽球 / 接着因子 / Rho / 血管形成 / 血球形成 / 細胞間相互作用 / 発生学

Outline of Final Research Achievements

I investigated how erythroblasts migrate into vascular tubes prior to onset of blood circulation. There were no apparent phenotypes in the zebrafish embryo which lacks an integrin beta-1 activity in erythroblasts. On the other hands, I found blood vessel abnormalities and cephalic hemorrhage in the endothelial cell-specific integrin beta-1 inhibition zebrafish. I revealed the integrin beta-1 functions in zebrafish and generated useful transgenic zebrafish line for related studies.

Academic Significance and Societal Importance of the Research Achievements

ヒトやマウスなどの哺乳類では、発生初期の母体内で進行する現象を観察することは容易ではない。生命活動に必須の血液循環が開始する機構も、この例外ではない。この点に関して、体外受精で体づくりが進行する魚類（ゼブラフィッシュ）を使うことで解決を試みた。特定の遺伝子の機能を任意の細胞で阻害できる技術を用い、血管内皮細胞でのインテグリンβ１の機能が血管形成とその維持に関わることを明らかにした。本研究で開発したゼブラフィッシュ系統は、他の研究にも応用することが可能であるため、国内外の共同研究先に譲渡できるように体制を整える。

Research Products

• [Int'l Joint Research] Max Planck Institute(ドイツ)
• [Journal Article] Rap1b promotes Notch signal-mediated hematopoietic stem cell development by enhancing integrin-mediated cell adhesion. (2019)
  • Author(s): Rho S., Kobayashi I., Oguri-Nakamura E., Ando K., Fujiwara M., Kamimura N., Hirata H., Iida A., Iwai Y., Mochizuki N., Fukuhara S.
  • Journal Title: Developmental Cell Volume: 印刷中 Issue: 5 Pages: 1-16
  • DOI: 10.1016/j.devcel.2019.03.023
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Focal adhesions are essential to drive zebrafish heart valve morphogenesis (2019)
  • Author(s): Gunawan Felix、Gentile Alessandra、Fukuda Ryuichi、Tsedeke Ayele Taddese、Jim?nez-Amilburu Vanesa、Ramadass Radhan、Iida Atsuo、Sehara-Fujisawa Atsuko、Stainier Didier Y.R.
  • Journal Title: The Journal of Cell Biology Volume: 218 Issue: 3 Pages: 1039-1054
  • DOI: 10.1083/jcb.201807175
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Integrin β1 activity is required for cardiovascular formation in zebrafish (2018)
  • Author(s): Iida Atsuo、Wang Zi、Hirata Hiromi、Sehara-Fujisawa Atsuko
  • Journal Title: Genes to Cells Volume: 23 Issue: 11 Pages: 938-951
  • DOI: 10.1111/gtc.12641
  • Peer Reviewed
• [Journal Article] The Sal-like 4 - integrin α6β1 network promotes cell migration for metastasis via activation of focal adhesion dynamics in basal-like breast cancer cells. (2017)
  • Author(s): Itou J, Tanaka S, Li W, Iida A, Sehara-Fujisawa A, Sato F, Toi M.
  • Journal Title: BBA Molecular Cell Research Volume: 1864 Issue: 1 Pages: 76-88
  • DOI: 10.1016/j.bbamcr.2016.10.012
  • NAID: 120005860049
  • Peer Reviewed
• [Journal Article] ADAM12-deficient zebrafish exhibit retardation in body growth at the juvenile stage without developmental defects (2016)
  • Author(s): Tokumasu Y, Iida A, Wang Z, Ansai S, Kinoshita M, Sehara-Fujisawa A
  • Journal Title: Development, Growth & Differentiation Volume: 58 Issue: 4 Pages: 409-421
  • DOI: 10.1111/dgd.12286
  • Peer Reviewed / Open Access
• [Journal Article] Generation of a transgenic medaka (Oryzias latipes) strain for visualization of nuclear dynamics in early developmental stages (2016)
  • Author(s): Inoue T, Iida A, Maegawa S, Sehara-Fujisawa A, Kinoshita M
  • Journal Title: Development, Growth & Differentiation Volume: 58 Issue: 9 Pages: 679-687
  • DOI: 10.1111/dgd.12324
  • Peer Reviewed
• [Presentation] ゼブラフィッシュを用いた血管・血球分化の研究 (2017)
  • Author(s): 飯田 敦夫
  • Organizer: 第３回血管生物若手研究会
• [Presentation] 小型魚類ゼブラフィッシュを使った発生機構の研究 (2017)
  • Author(s): 飯田 敦夫
  • Organizer: 第2回次世代生命科学の研究会
• [Presentation] メダカ受精卵の前核および細胞核の生きた状態での可視化 (2016)
  • Author(s): 井上 喬允，飯田 敦夫，前川 真吾，瀬原 淳子，木下 政人
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-11-30
• [Presentation] Analysis of non-mammalian viviparous vertebrate using a livebearer fish Xenotoca eiseni (2016)
  • Author(s): Atsuo Iida, Toshiyuki Nishimaki, Atsuko Sehara-Fujisawa
  • Organizer: 第22回国際動物学会 第87回日本動物学会 合同大会
  • Place of Presentation: 沖縄県
  • Year and Date: 2016-11-14
  • Int'l Joint Research / Invited
• [Presentation] マウスてで肥満に関わるADAM12遺伝子のゼブラフィッシュ変異体の樹立 (2016)
  • Author(s): 徳増 雄大，飯田 敦夫，王 梓，安齋 賢，木下 政人，瀬原 淳子
  • Organizer: 第2回ゼブラフィッシュ創薬研究会
  • Place of Presentation: みんなの森 ぎふメディアコスモス