| Project/Area Number |
15H02577
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Orthodontics/Pediatric dentistry
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| Research Institution | Osaka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
伊藤 慎将 大阪大学, 歯学研究科, 助教 (40633706)
黒坂 寛 大阪大学, 歯学部附属病院, 講師 (20509369)
三原 聖美 大阪大学, 歯学研究科, 招へい教員 (00551920)
中川 一路 京都大学, 医学研究科, 教授 (70294113)
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥41,990,000 (Direct Cost: ¥32,300,000、Indirect Cost: ¥9,690,000)
Fiscal Year 2018: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2017: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2016: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2015: ¥23,660,000 (Direct Cost: ¥18,200,000、Indirect Cost: ¥5,460,000)
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| Keywords | 口蓋裂 / Runx1 / Cbfb / Stat3 / Tgfb3 / Lgr5 / サービカルループ / 切歯 / 幹細胞 / 口蓋上皮の癒合 / Runxシグナル / ゲノム編集 / 歯学 / バイオテクノロジー / 発生・分化 / 口蓋 / 歯 / 遺伝子改変動物 |
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| Outline of Final Research Achievements |
Craniofacial development including palatogenesis and tooth development is regulated by various genes and by complicated molecular pathway. In this research project using various mutant mice and new methodology including genome editing, we found the following new findings. In palatogenesis, we found a new signaling axis of Runx1/Cbfb-pStat3-Tgfb3, which regulated the epithelial fusion in the anterior regions. Furthermore, Socs3, a negative regulator of Stat3 phosphorylation, was regulated by Runx1 signaling. We also found that Stat3 phosphorylation is important in the maintenance of the stem cell in the growing incisors. Our study showed that Runx1-pStat3-Lgr5 signaling pathway maintained the stem cells in the cervical loop. Interestingly, activation of Stat3 phosphorylation rescued the incisor phonotypes of Runx1/Cbfb mutants that demonstrated the disturbed continuous growth of the dental epithelium. Together, we found novel roles of Stat3 phosphorylation in craniofacial morphogenesis.
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| Academic Significance and Societal Importance of the Research Achievements |
口唇口蓋裂や歯の欠損・形成不全等の口腔の先天性疾患の分子機構の解明は、将来の診断・予防・治療の発展のために不可欠である。口唇口蓋裂や歯の形成異常は複数の病原遺伝子が関与し、病原遺伝子の同定とその分子間ネットワークの理解は重要である。本研究によって、Statシグナルをはじめ、形態形成で重要な役割を果たす分子が明らかになった。そして、これらを制御することで、疾患の治療につながる基盤的な所見が得られた。
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