Epigenetic regulation of dedifferentiation-inducible genes mediated by macrophage during regeneration

• Project/Area Number: 18K06184
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43050:Genome biology-related
• Research Institution: Okayama University
• Principal Investigator: Bando Tetsuya 岡山大学, 医歯薬学域, 講師 (60423422)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: コオロギ / 再生 / 再生芽細胞 / マクロファージ / Toll / Toll受容体 / TLR / エピゲノム / 再生芽 / 脱分化 / 昆虫

Outline of Final Research Achievements

The two-spotted cricket Gryllus bimaculatus regenerates the lost part of leg. During the leg regeneration process, the blastema, which is the population of undifferentiated-proliferating cells, is formed beneath the wound epithelium. The blastema cells proliferate and differentiate to regenerate the lost part of leg, however, molecular mechanisms of the blastema formation are unclear. In this study, we found that the plasmatocytes, which are known as insect macrophages, recognized debris of injured cells and accumulated into the wound site. The plasmatocytes produced the insect cytokine Upd to activate Jak/STAT signaling, inducing the blastema cell proliferation and leg regeneration.

Academic Significance and Societal Importance of the Research Achievements

様々な生物の器官再生に、免疫細胞の一種であるマクロファージが重要であることが分かっているが、マクロファージが器官再生を促進する詳細なメカニズムは不明であった。我々は、Toll受容体シグナルが昆虫のマクロファージの遊走を促進することがきっかけとなり、器官再生が促進されることを見出した。これまで無関係と思われていた器官の再生と個体の免疫の関連を明らかにした。

Research Products

• [Journal Article] Toll signalling promotes blastema cell proliferation during cricket leg regeneration via insect macrophages (2022)
  • Author(s): Tetsuya Bando, Misa Okumura, Yuki Bando, Marou Hagiwara, Yoshimasa Hamada, Yoshiyasu Ishimaru, Taro Mito, Eri Kawaguchi, Takeshi Inoue, Kiyokazu Agata, Sumihare Noji, Hideyo Ohuchi
  • Journal Title: Development Volume: 149(8) Issue: 8 Pages: 1-14
  • DOI: 10.1242/dev.199916
  • Peer Reviewed / Open Access
• [Journal Article] Insights into the genomic evolution of insects from cricket genomes (2021)
  • Author(s): Guillem Ylla, Taro Nakamura, Takehiko Itoh, Rei Kajitani, Atsushi Toyoda, Sayuri Tomonari, Tetsuya Bando, Yoshiyasu Ishimaru, Takahito Watanabe, Masao Fuketa, Yuji Matsuoka, Austen A. Barnett, Sumihare Noji, Taro Mito & Cassandra G. Extavour
  • Journal Title: Communications Biology Volume: 4 Issue: 1 Pages: 733-733
  • DOI: 10.1038/s42003-021-02197-9
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] フタホシコオロギが解き明かす免疫と再生の思いがけない関係 (2021)
  • Author(s): 板東 哲哉, 奥村 美紗, 濱田 良真, 大内 淑代
  • Journal Title: 昆虫と自然 Volume: 57 Pages: 33-36
• [Journal Article] Dkk3/REIC, an N-glycosylated Protein, Is a Physiological Endoplasmic Reticulum Stress Inducer in the Mouse Adrenal Gland (2020)
  • Author(s): Fujita, H., Bando, T., Oyadomari, S., Ochiai, K., Watanabe, M., Kumon, H. & Ohuchi, H.
  • Journal Title: Acta Medica Okayama Volume: 74 Issue: 3 Pages: 199-208
  • DOI: 10.18926/AMO/59950
  • NAID: 120006862792
  • URL: https://ousar.lib.okayama-u.ac.jp/59950
  • Peer Reviewed / Open Access
• [Journal Article] Fgf10-CRISPR mosaic mutants demonstrate the gene dose-related loss of the accessory lobe and decrease in the number of alveolar type 2 epithelial cells in mouse lung (2020)
  • Author(s): Habuta, M., Yasue, A., Suzuki, K. I. T., Fujita, H., Sato, K., Kono, H., Takayama, A., Bando, T., Miyaishi, S., Oyadomari, S., Tanaka, E. & Ohuchi, H.
  • Journal Title: PloS one Volume: 15 Issue: 10 Pages: e0240333-e0240333
  • DOI: 10.1371/journal.pone.0240333
  • NAID: 120006959727
  • Peer Reviewed / Open Access
• [Journal Article] Functional analysis of Pdp1 and vrille in the circadian system of a cricket (2020)
  • Author(s): Narasaki-Funo, Y., Tomiyama, Y., Nose, M., Bando, T. & Tomioka, K.
  • Journal Title: Journal of Insect Physiology Volume: 127 Pages: 104156-104156
  • DOI: 10.1016/j.jinsphys.2020.104156
  • Peer Reviewed
• [Journal Article] The role of clockwork orange in the circadian clock of the cricket Gryllus bimaculatus (2020)
  • Author(s): Tomiyama, Y., Shinohara, T., Matsuka, M., Bando, T., Mito, T. & Tomioka, K.
  • Journal Title: Zoological Letters Volume: 6 Issue: 1 Pages: 12-12
  • DOI: 10.1186/s40851-020-00166-4
  • NAID: 120006937503
  • Peer Reviewed / Open Access
• [Journal Article] Localization of the ultraviolet-sensor Opn5m and its effect on myopia-related gene expression in the late-embryonic chick eye. (2019)
  • Author(s): Kato M, Sato K, Habuta M, Fujita H, Bando T, Morizane Y, Shiraga F, Miyaishi S, Ohuchi H.
  • Journal Title: Biochem Biophys Rep. Volume: 19 Pages: 100665-100665
  • DOI: 10.1016/j.bbrep.2019.100665
  • NAID: 120006733898
  • Peer Reviewed / Open Access
• [Journal Article] Dickkopf3 (Dkk3) is required for maintaining the integrity of secretory vesicles in the mouse adrenal medulla. (2019)
  • Author(s): Habuta M, Fujita H, Sato K, Bando T, Inoue J, Kondo Y, Miyaishi S, Kumon H, Ohuchi H.
  • Journal Title: Cell Tissue Res. Volume: 379 Issue: 1 Pages: 157-167
  • DOI: 10.1007/s00441-019-03113-8
  • Peer Reviewed
• [Journal Article] Molecular mechanisms of limb regeneration: insights from regenerating legs of the cricket Gryllus bimaculatus. (2018)
  • Author(s): Bando T, Mito T, Hamada Y, Ishimaru Y, Noji S, Ohuchi H.
  • Journal Title: The International Journal of Developmental Biology Volume: 62 Pages: 559-569
  • Peer Reviewed
• [Journal Article] Wound repair, remodeling, and regeneration. (2018)
  • Author(s): Bando T, Yokoyama H, Nakamura H.
  • Journal Title: Development, Growth & Differentiation Volume: 60 Issue: 6 Pages: 303-305
  • DOI: 10.1111/dgd.12566
  • Peer Reviewed
• [Journal Article] Bone morphogenetic protein signaling in distal patterning and intercalation during leg regeneration of the cricket, Gryllus bimaculatus. (2018)
  • Author(s): Ishimaru Y, Bando T, Ohuchi H, Noji S, Mito T.
  • Journal Title: Development, Growth & Differentiation Volume: 60 Issue: 6 Pages: 377-386
  • DOI: 10.1111/dgd.12560
  • NAID: 120007168253
  • Peer Reviewed / Open Access
• [Journal Article] A novel photic entrainment mechanism for the circadian clock in an insect: involvement of c-fos and cryptochromes (2018)
  • Author(s): Kutaragi Y, Tokuoka A, Tomiyama Y, Nose M, Watanabe T, Bando T, Moriyama Y, Tomioka K.
  • Journal Title: Zoological Letters Volume: 4 Issue: 1 Pages: 26-26
  • DOI: 10.1186/s40851-018-0109-8
  • Peer Reviewed / Open Access
• [Presentation] Toll受容体と活性酸素による昆虫の器官再生の制御 (2022)
  • Author(s): 板東哲哉、奥村美紗、大内淑代
  • Organizer: 第127回日本解剖学会総会・全国学術集会
• [Presentation] NADPH oxidasesによるコオロギ脚再生の制御メカニズム (2021)
  • Author(s): 板東哲哉、奥村美紗、大内淑代
  • Organizer: 第44回日本分子生物学会年会（MBSJ2021）
• [Presentation] 昆虫脚再生におけるToll様受容体とCD36による再生芽細胞の増殖の制御 (2021)
  • Author(s): 板東 哲哉、奥村 美紗、大内 淑代
  • Organizer: 第126回 日本解剖学会総会・全国学術集会 第98回 日本生理学会大会 合同大会
• [Presentation] Toll様受容体とスカベンジャー受容体CD36による昆虫の器官再生メカニズム (2020)
  • Author(s): 板東哲哉，奥村美紗，坂東優希，萩原万優，大内淑代
  • Organizer: 第125回日本解剖学会総会・全国学術集会
• [Presentation] Toll受容体によるコオロギ脚再生の促進メカニズム (2019)
  • Author(s): 奥村美紗、板東哲哉、坂東優希、萩原万優、大内淑代
  • Organizer: 第４２回日本分子生物学会年会
• [Presentation] Innate immunity signaling pathways promote leg regeneration in the cricket (2018)
  • Author(s): Bando T, Okumura M, Hagiwara M, Hamada Y, Mito T, Noji S, Ohuchi H.
  • Organizer: 第70回日本細胞生物学会 第51回日本発生生物学会 合同大会
• [Presentation] マクロファージによる器官再生の促進：昆虫の脚再生をモデルとして (2018)
  • Author(s): 板東哲哉，奥村美紗，坂東優希，萩原万優子，濱田良真，大内淑代
  • Organizer: 日本解剖学会 第７３回中国・四国支部学術集会
• [Presentation] 極性分子複合体はコオロギ脚再生に必要である (2018)
  • Author(s): 板東哲哉、濱田良真、三戸太郎、野地澄晴、大内淑代
  • Organizer: 第41回日本分子生物学会年会
• [Remarks] 免疫に働くToll受容体がコオロギの再生を促進するメカニズムを解明
  • URL: https://www.okayama-u.ac.jp/tp/release/release_id900.html
• [Remarks] Okayama University Medical Research Updates
  • URL: https://www.okayama-u.ac.jp/tp/news/news_id11026.html