| Project/Area Number |
15K08272
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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 medical chemistry
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| Research Institution | Osaka University |
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Principal Investigator |
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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 |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 外分泌腺 / 唾液腺 / Wnt / 腺房 / 導管 / 分化 / KIT / Wntシグナル / 腺房分化 / 導管形成 |
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| Outline of Final Research Achievements |
Growth factor signaling is involved in the development of various tubular organs, but how signaling regulates organ early morphogenesis and late differentiation remains to be clarified. Experiments using genetically manipulated mice and organ cultures revealed that Wnt signaling at early stage of submandibular salivary gland (SMG) development inhibits end bud differentiation into proacini by suppressing KIT expression through the upregulation of the transcription factor Myb. In addition, Wnt signaling at the SMG development early stage promoted the expansion of end bud progenitor, leading to duct structure formation. In contrast, Wnt signaling reduction at a late stage of SMG development promoted end bud differentiation into proacini and suppressed duct morphogenesis. These results suggest that Wnt signaling activity fine-tunes the timing of end bud morphogenesis and differentiation into proacini, in co-operation with KIT signaling during salivary gland organogenesis.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、胎生期唾液腺をモデルとして、今回新たに確立した各種上皮単独培養法を用いて、生体内で起きている複雑な形態形成と分化のプロセスをin vitroで再現した。
本研究成果は種々の管腔臓器の発生と再生の仕組みを理解するための分子基盤を提供するものであり、再生医療を現実のものにするための必須の事項である。また、正常な組織形成・維持のメカニズムの解明はその破綻に基づくがんの病態を理解する上でも重要であり、本研究は学術的に重要であるばかりでなく、医療という側面において社会的意義も大きい。
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