Exploring the molecules regulating mesothelial EMT during chorio-allantoic fusion

• Project/Area Number: 18K06265
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 44020:Developmental biology-related
• Research Institution: Kumamoto University
• Principal Investigator: Nagai Hiroki 熊本大学, 国際先端医学研究機構, リサーチ・スペシャリスト (80772508)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 漿尿膜融合 / 中皮EMT / ニワトリ胚モデル / EMT / ニワトリ胚 / 上皮間葉転換 / 中皮細胞 / 胚発生 / 胚体外組織

Outline of Final Research Achievements

Mesothelial EMT (Epithelial-Mesenchymal Transition) plays important roles in various aspects, including development and progression of human disorders and organogenesis in embryo development. Despite the importance of understanding the regulatory mechanism of mesothelial EMT, however, little is known about the molecules regulating mesothelial EMT. With a novel mesothelial EMT model called chorio-alantoic fusion in chicken embryo, we explored the regulatory molecules driving the mesothelial EMT taking place on chorion mesothelium and allantois mesothelium during the fusion process. This study have revealed that the factors, including EMT core transcription factors, WNT and TGF siganling molecules, and mesothelioma marker WT1, are involved in molecular rergualtion of mesothelial EMT during chicken chorio-allantoic fusion.

Academic Significance and Societal Importance of the Research Achievements

上皮間葉転換(EMT)は、ガンの浸潤や転移に深く関与する現象としてよく知られており、ガン制圧の標的として勢力的に研究がなされている。中皮EMTは、中皮腫や卵巣ガン、肺繊維症などのヒト疾患の発生とその進行プロセスに深く関わっている。また胎児の正常発生においても、心臓や腸への血管平滑筋細胞の供給などを通して、重要な役割を担っている。本研究で得られた知見は、中皮細胞性疾患の病態や正常組織発生の中皮EMTの理解促進という観点において、その一端に少なからず寄与できるものと考える

Research Products

• [Journal Article] Partial EMT/MET: An Army of One (2020)
  • Author(s): Hamidi Sofiane、Nagai Hiroki、Sheng Guojun
  • Journal Title: Methods in Molecular Biology Volume: - Pages: 29-33
  • DOI: 10.1007/978-1-0716-0779-4_5
  • ISBN: 9781071607787, 9781071607794
  • Peer Reviewed
• [Journal Article] NPAS4L is involved in avian hemangioblast specification (2020)
  • Author(s): Wei Weng、Hiroki Nagai、Sofiane Hamidi、Guojun Sheng
  • Journal Title: Haematologica Volume: 105 Issue: 11 Pages: 2647-2650
  • DOI: 10.3324/haematol.2019.239434
  • Peer Reviewed / Open Access
• [Journal Article] Mesenchymal-epithelial transition regulates initiation of pluripotency exit before gastrulation (2020)
  • Author(s): Sofiane Hamidi, Yukiko Nakaya, Hiroki Nagai, Cantas Alev, Takeya Kasukawa, Sapna Chhabra, Ruda Lee, Hitoshi Niwa, Aryeh Warmflash, Tatsuo Shibata, Guojun Sheng
  • Journal Title: Development Volume: - Issue: 3 Pages: 184960-184960
  • DOI: 10.1242/dev.184960
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Biomechanical regulation of EMT and epithelial morphogenesis in amniote epiblast. (2019)
  • Author(s): Hamidi S, Nakaya Y, Nagai H, Alev C, Shibata T, Sheng G.
  • Journal Title: Physical Biology Volume: 4 Issue: 4 Pages: 041002-041011
  • DOI: 10.1088/1478-3975/ab1048
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Early hematopoietic and vascular development in the chick (2018)
  • Author(s): Nagai Hiroki、Shin Masahiro、Weng Wei、Nakazawa Fumie、Jakt Lars Martin、Alev Cantas、Sheng Guojun
  • Journal Title: The International Journal of Developmental Biology Volume: 62 Issue: 1-2-3 Pages: 137-144
  • DOI: 10.1387/ijdb.170291gs
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Mesothelial EMT during chorio-allantoic fusion in chick early development. (2019)
  • Author(s): Hiroki Nagai, Guojun Sheng.
  • Organizer: 第42回日本分子生物学会年会
• [Presentation] Mesothelial EMT during chorio-allantoic fusion in chick early development (2019)
  • Author(s): Hiroki Nagai, Guojun Sheng.
  • Organizer: The 9th EMT International Association Meeting
  • Int'l Joint Research
• [Presentation] Involvement of Epithelial-Mesenchymal Transition in Avian Chorioallantoic Fusion (2018)
  • Author(s): Nagai Hiroki, Sheng Guojun.
  • Organizer: Avian Model Systems 10
  • Int'l Joint Research
• [Remarks] IRCMS website _What's new : March 15, 2019.
  • URL: http://ircms.kumamoto-u.ac.jp/reviews_books/2019/03/201904-2.html
• [Remarks] IRCMS website _What's new : December 1, 2018.
  • URL: http://ircms.kumamoto-u.ac.jp/reviews_books/2018/12/201904-5.html