Novel functions of Runx genes as causal genes for ectodermal dysplasia

• Project/Area Number: 24249093
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthodontic/Pediatric dentistry
• Research Institution: Osaka University (2013-2014); Okayama University (2012)
• Principal Investigator: Yamashiro Takashi 大阪大学, 歯学研究科(研究院), 教授 (70294428)
• Co-Investigator(Kenkyū-buntansha): 川邉 紀章 岡山大学, 医歯(薬)学総合研究科, 准教授 (00397879) ; 村上 隆 岡山大学, 大学病院, 講師 (00534786) ; 伊藤 慎将 大阪大学, 歯学研究科(研究院), 助教 (40633706) ; 上岡 寛 岡山大学, 医歯(薬)学総合研究科, 教授 (80253219) ; 柳田 剛志 岡山大学, 大学病院, 講師 (90534793)
• Co-Investigator(Renkei-kenkyūsha): NAKAGAWA ICHIRO 京都大学, 医学研究科, 教授 (70294113)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥45,240,000 (Direct Cost: ¥34,800,000、Indirect Cost: ¥10,440,000); Fiscal Year 2014: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2013: ¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000); Fiscal Year 2012: ¥21,710,000 (Direct Cost: ¥16,700,000、Indirect Cost: ¥5,010,000)
• Keywords: Runxシグナリング / 上皮間葉相互作用 / 器官形成 / Cbfb / Runx1 / 唾液腺 / 歯 / 皮膚付属器官 / Ｃｂｆｂ / 切歯 / 臼歯

Outline of Final Research Achievements

In this study, we investigated the possible roles of epithelial Runx1/Cbfb signaling in the organogenesis and craniofacial development. Using the epithelial-specific Runx1 knock-out and epithelial-specific Cfbf knock-out mice, we provided evidence that Runx1/Cbfb has indispensable roles in the development of the teeth, the salivary gland, and the palate. In salivary gland, Runx1 is involved in sexual dimorphism in the induction of the granular convoluted tubules of the submandibular gland in the presence of androgen. In the incisors, Runx1 is involved in the regulation of Lgr5-positive epithelial stem cells that differentiate into ameloblasts, through regulation of phosphorylation of Stat3 in the cervical loop of the growing incisors. In the palate, Runx1 epithelial-specific deletion led to the failed disintegration of the contacting palatal epithelium and that Tgfb3 is a critical downstream target in the pathogenesis of anterior cleft palate in the mutants.

Research Products

• [Journal Article] Runx/Cbfb signaling regulates postnatal development of granular convoluted tubule in the mouse submandibular gland. (2015)
  • Author(s): Islam MN, Itoh S, Yanagita T, Sumiyoshi K, Hayano S, Kuremoto K, Kurosaka H, Honjo T, Kawanabe N, Kamioka H, Sakai T, Ishimaru N, Taniuchi I, Yamashiro T
  • Journal Title: Dev Dyn. Volume: 244 Pages: 488-496
  • Peer Reviewed
• [Journal Article] Isolation and characterization of SSEA-4-positive subpopulation of human deciduous dental pulp cells. (2015)
  • Author(s): Kawanabe N, Fukushima H, Ishihara Y, Yanagita T, Kurosaka H, Yamashiro T
  • Journal Title: Clin Oral Investig. Volume: 19 Issue: 2 Pages: 363-371
  • DOI: 10.1007/s00784-014-1260-z
  • Peer Reviewed / Open Access
• [Journal Article] Topical application of lithium chloride on the pulp induces dentin regeneration. (2015)
  • Author(s): Ishimoto K, Hayano S, Yanagita T, Kurosaka H, Kawanabe N, Itoh S, Ono M, Kuboki T, Kamioka H, Yamashiro T.
  • Journal Title: PLoS One Volume: 10 Issue: 3 Pages: 1-12
  • DOI: 10.1371/journal.pone.0121938
  • Peer Reviewed / Open Access
• [Journal Article] Ex vivo real-time observation of Ca(2+) signaling in living bone in response to shear stress applied on the bone surface. (2013)
  • Author(s): Ishihara Y
  • Journal Title: Bone. Volume: 53(1) Pages: 204-15
  • Peer Reviewed
• [Journal Article] Cartilage-Specific Over-Expression of CCN Family Member 2/Connective Tissue Growth Factor (CCN2/CTGF) Stimulates Insulin-Like Growth Factor Expression and Bone Growth. (2013)
  • Author(s): Tomita N
  • Journal Title: PLoS One. Volume: 8(3)
  • Peer Reviewed
• [Journal Article] The early mouse 3D osteocyte network in the presence and absence of mechanical loading. (2013)
  • Author(s): Sugawara Y
  • Journal Title: Bone Volume: 52(1) Pages: 189-96
  • Peer Reviewed
• [Journal Article] Promotion of Ccn2 expression and osteoblastic differentiation by actin polymerization, which is induced by laminar fluid flow stress. (2012)
  • Author(s): Honjo T
  • Journal Title: J Cell Commun Signal. Volume: 6(4) Pages: 225-32
  • Peer Reviewed
• [Journal Article] SSEA-4 is a marker of human deciduous periodontal ligament stem cells. (2012)
  • Author(s): Fukushima H
  • Journal Title: J Dent Res. Volume: 91(10) Pages: 955-60
• [Journal Article] Microscale fluid flow analysis in a human osteocyte canaliculus using a realistic high-resolution image-based three-dimensional model. (2012)
  • Author(s): Kamioka H
  • Journal Title: Integr Biol (Camb) Volume: 4(10) Pages: 1198-206