The Mechanism of Palatal Shelve Induction

• Project/Area Number: 17K11829
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Niigata University
• Principal Investigator: Kawasaki Maiko 新潟大学, 医歯学系, 准教授 (40584587)
• Co-Investigator(Kenkyū-buntansha): 前田 健康 新潟大学, 医歯学系, 教授 (40183941) ; 大峡 淳 新潟大学, 医歯学系, 教授 (40266169) ; 川崎 勝盛 新潟大学, 医歯学系, 助教 (40529640)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 一次繊毛 / 口蓋裂 / 繊毛病 / Ofd1 / OFD1 / 発生・分化

Outline of Final Research Achievements

The role of the primary cilia in maxillary bone development is not fully understood. We generated mice with a mesenchymal conditional deletion of Ift88 and Ofd1 using the Wnt1Cre mice. These proteins involved in the function and formation of primary cilia. It has been shown that Ift88 and Ofd1 KO mice exhibit cleft palate and ectopic bone. We also found ectopic apoptosis in the both mutants maxillary process at an early stage of development. To investigate whether the ectopic apoptosis is related to the both maxillary phenotypes, we generated Ift88 and p53 WKO mutants to reduce apoptosis. These mice showed no excess bone formation, suggesting that the cells evading apoptosis by the presence of Ift88 in wild-type mice limit bone formation in maxillary development. On the other hand, the palatal cleft was retained in this mice, indicating that the excess bone formation or abnormal apoptosis was independent of the cleft palate phenotype in Ift88 mutant mice.

Academic Significance and Societal Importance of the Research Achievements

これまで停滞していた口蓋突起形成開始ポイントにおける分子レベルでの解析が、Ofd1欠損マウスを使用する事により、初めて大幅な発展が望める。さらに、本研究課題は、分子単位、細胞単位、細胞小器官単位、動物単位からという様々な角度の切り口からのアプローチであり、歯科領域にとどまらない結果が期待できる。そして、哺乳類の口蓋の特殊性は、分子レベルでまったく証明されていない。本研究課題が哺乳類誕生に対する長年の疑問への回答となる可能性が高い。このようにOfd1による口蓋形成メカニズム研究は、他の器官研究へも広がる要素を持つ。基礎研究としてのみならず、生物学や臨床分野と幅広く分野への貢献が可能となる。

Research Products

• [Journal Article] Ift88 limits bone formation in maxillary process through suppressing apoptosis. (2019)
  • Author(s): Watanabe M, Kawasaki M, Kawasaki K, Kitamura A, Nagai T, Kodama Y, Meguro F, Yamada A, Sharpe PT, Maeda T, Takagi R, Ohazama A.
  • Journal Title: Arch Oral Biol Volume: 101 Pages: 43-50
  • DOI: 10.1016/j.archoralbio.2019.02.017
  • Peer Reviewed
• [Journal Article] Expanding the Oro-Dental and Mutational Spectra of Kabuki Syndrome and Expression of KMT2D and KDM6A in Human Tooth Germs. (2018)
  • Author(s): Porntaveetus T, Abid MF, Theerapanon T, Srichomthong C, Ohazama A, Kawasaki K, Kawasaki M, Suphapeetiporn K, Sharpe PT, Shotelersuk V.
  • Journal Title: Int J Biol Sci. Volume: 14(4) Issue: 4 Pages: 381-389
  • DOI: 10.7150/ijbs.23517
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] The Role of Primary Cilia in Craniofacial Development. (2018)
  • Author(s): Kawasaki M, Kawasaki K, Ohazama A.
  • Organizer: International Collaborative Symposium on Development of Human Resources in Practical Oral Health and treatment
  • Int'l Joint Research
• [Presentation] he Role of Primary Cilia in Tongue Development. (2017)
  • Author(s): Kawasaki M, Kawasaki K, Ohazama A.
  • Organizer: Niigata-Taiwan University Dental Research Symposium.
  • Int'l Joint Research