Study on the molecular basis of the position-specific formation of the hair cells and sensory neurons in the inner ear
| Project/Area Number |
16K08453
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General anatomy (including histology/embryology)
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| Research Institution | Jichi Medical University |
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Principal Investigator |
SATO shigeru 自治医科大学, 医学部, 准教授 (70306108)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 感覚器形成 / 内耳形成 / 有毛細胞 / 転写制御 / エンハンサー / 遺伝子改変動物 / ホメオボックス遺伝子 / Six遺伝子 / 内耳有毛細胞 / 難聴 / Six1 / Atoh1 / 突然変異マウス / クロマチン高次構造 / 内耳 / 蝸牛 / 感覚神経 / マウス / 蝸牛有毛細胞 / 感覚器プラコード / ニワトリ胚 / Cre-loxシステム / 再生医療 / 難聴モデルマウス |
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| Outline of Final Research Achievements |
The vertebrate inner ear responsible for hearing and balance is one of the most complex organs. This study aimed to understand the regulation and function of the key homeobox gene Six1. We carried out ATAC-seq analysis using hair cells isolated from E17.5 mouse embryos, and identified 7 candidate hair cell-enhancers located in the Six1-TAD. In addition, SIX1-binding sequences were enriched in top 1,105 hair cell-specific ATAC-seq peaks. This strongly suggest that SIX1 controls not only Atoh1 but also many hair cell genes and acts as the key transciption factor characterizing hair cells. We also established a new Six1-flox mouse strain and crossed them with mice expressing Cre in the otic placode, sensory neurons, hair cells and surrounding mesoderm. These mice should allow us a deeper understanding of the function of Six1 during the formation of the inner ear.
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| Academic Significance and Societal Importance of the Research Achievements |
脊椎動物の内耳は最も精巧な器官の一つであり、聴覚と平衡覚を司る。本研究は、内耳の形成に重要なSix1遺伝子に注目した研究を進めた。その結果、有毛細胞でSix1がはたらくために必須なスイッチを同定できた。また、Six1が多数の遺伝子を活性化し有毛細胞を特徴づける転写因子であることもわかってた。Six1の機能のさらなる理解に役立つマウス系統も作った。本研究は内耳形成、難聴の理解・再生医療に役立つ。
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Report
(4 results)
Research Products
(5 results)
