Regulation and analysis of tooth and salivary gland morphogenesis

• Project/Area Number: 26293433
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Orthodontics/Pediatric dentistry
• Research Institution: Tohoku University
• Principal Investigator: FUKUMOTO EMIKO 東北大学, 歯学研究科(研究院), 大学院非常勤講師 (10264251)
• Co-Investigator(Kenkyū-buntansha): 福本 敏 東北大学, 歯学研究科(研究院), 教授 (30264253) ; 齋藤 正寛 東北大学, 歯学研究科(研究院), 教授 (40215562) ; 阪井 丘芳 大阪大学, 歯学研究科(研究院), 教授 (90379082) ; 保住 建太郎 東京薬科大学, 薬学部, 講師 (10453804)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000); Fiscal Year 2016: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2015: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2014: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
• Keywords: 歯の発生 / 形態形成 / 唾液腺 / 再生 / 発生・分化 / 歯胚

Outline of Final Research Achievements

To regenerate of tooth and salivary gland, it is important to identify the gene associated with the regulation of morphogenesis. However, it has never clearly understood the morphogenesis of tooth and salivary gland. Here, we identified the genes specifically expressed in tooth germ using microarray gene screening.
Mst1 is one of the Hippo pathway molecule expressed in embryonic tooth germ. Over expression of Mst1 in dental epithelial cells showed inhibition of proliferation. On the other hand, suppression of Mst1 expression using siRNA showed enhanced proliferation. Further, knockdown of Mob1 in mice, which is down stream molecule of Mst1, showed enhanced tooth size. Moreover, we identified the regulation of tooth width by NF-kB singaling molecule, NIK and p50. Further, GDF5 down-regulated enamel formation. These information is useful for establish the regeneration of tooth and salivary gland.

Research Products

• [Int'l Joint Research] 北京大学(中国)
• [Journal Article] Nephronectin plays critical roles in Sox2 expression and proliferation in dental epithelial stem cells via EGF-like repeat domains. (2017)
  • Author(s): Arai C, Yoshizaki K, Miyazaki K, Saito K, Yamada A, Han X, Funada K, Fukumoto E, Haruyama N, Iwamoto T, Takahashi I, Fukumoto S.
  • Journal Title: Sci Rep. Volume: 27 Issue: 1 Pages: 45181-45181
  • DOI: 10.1038/srep45181
  • NAID: 120006534986
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Geminin is an indispensable inhibitor of Cdt1 in mouse embryonic stem cells. (2017)
  • Author(s): Hosogane, M., Bosu, L., Fukumoto, E., Yamada, H., Sato, S., Nakayama, K.
  • Journal Title: Genes Cells Volume: 印刷中 Issue: 4 Pages: 360-375
  • DOI: 10.1111/gtc.12482
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Mutant GDF5 enhances ameloblast differentiation via accelerated BMP2-induced Smad1/5/8 phosphorylation (2016)
  • Author(s): Liu J, Saito K*, Maruya Y, Nakamura T, Yamada A, Fukumoto E, Ishikawa M, Iwamoto T, Miyazaki K, Yoshizaki K, Ge L, Fukumoto S
  • Journal Title: Scientific reports Volume: 6 Issue: 1 Pages: 23670-23670
  • DOI: 10.1038/srep23670
  • NAID: 120006534957
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Connexin 43 is necessary for salivary gland branching morphogenesis and FGF10-induced ERK1/2 phosphorylation (2016)
  • Author(s): Yamada A, Futagi M, Fukumoto E, Saito K, Yoshizaki K, Ishikawa M, Arakaki M, Hino R, Sugawara Y, Ishikawa M, Naruse M, Miyazaki K, Nakamura T, Fukumoto S.
  • Journal Title: The Journal of Biological Chemistry Volume: 291 Issue: 2 Pages: 904-912
  • DOI: 10.1074/jbc.m115.674663
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Interaction between Fibronectin and β1 Integrin is Essential for Tooth Development. (2015)
  • Author(s): Saito, K., Fukumoto, E., Yamada, A., Yuasa, K., Yoshizaki, K., Iwamoto, T., Saito, M., Nakamura, T., and Fukumoto, S.
  • Journal Title: PLOS one Volume: 10(4) Issue: 4 Pages: 1-12
  • DOI: 10.1371/journal.pone.0121667
  • NAID: 120006872347
  • Peer Reviewed / Open Access