| Project/Area Number |
13470003
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General anatomy (including Histology/Embryology)
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| Research Institution | Kyoto University |
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Principal Investigator |
SHIOTA Kouhei Kyoto Univ, Grad Sch of Med, Professor, 医学研究科, 教授 (80109529)
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| Co-Investigator(Kenkyū-buntansha) |
MORIMOTO Takeshi Kyoto Univ, Grad Sch of Med, Instructor, 医学研究科, 助手 (00311746)
TAKIGAWA Toshiya Kyoto Univ, Grad Sch of Med, Instructor, 医学研究科, 助手 (90263095)
ISHIBASHI Makoto Kyoto Univ, Grad Sch of Med, Lecturer, 医学研究科, 講師 (30232341)
SEKI Kenji Kyoto Univ, Grad Sch of Med, Instructor, 医学研究科, 助手 (60362505)
三浦 岳 京都大学, 医学研究科, 助手 (10324617)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2003: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2002: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2001: ¥7,000,000 (Direct Cost: ¥7,000,000)
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| Keywords | Sonic hedgehog (Shh) / Indian hedgehog (Ihh) / Fibroblast growth factor (Fgf) / Bone-morphogenetic protein (BMP) / Development / Differentiation / Brain / Lung / Sonic hedgebog / Fibroblast growth factor / Bone morphogenetic protein / シグナル / 神経分化 / 間脳 / 中脳 / 全前脳胞症 / 肺原基 / 反応-拡散モデル / Sonic hedgehog / FGF / 遺伝子ノックアウトマウス / 発生異常 / 器官培養 / 数理モデル |
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| Research Abstract |
1) Shh gene regulates the development of the brain and spinal cord, especially the differentiation of the ventral neurons. We analyzed the phenotype of mouse embryos lacking Shh and found that Shh-dependent signaling relay regulates proliferation and survival of dorsal cell populations in the diencephalon and midbrain. It was also found that in the diencephalons/midbrain of the mouse embryo, FgF15 is directly regulated by Glitranscription factors and Gli2 plays a central role in this regulation.
2) During lung branching morphogenesis, the interction of positive and inhibitory signals play a crucial role. Using lung bud organ culture, we found that depletion of FGF acts as a lateral inhibitory factor in branching morphogenesis but bone morphogenetic protein (BMP) 4 do not substitute for the inhibitory effect. Based on the experimental result, we constructed a reaction-diffusion model and concluded that FGF may be a key regulatory component in the initial phase of branching morphogenesis of the lung bud epithelium.
3) Using a chromatin immunoprecipitation-based gene cloning method, we identified the Indian hedgehog (Ihh) gene as a target of BMP signaling. Both reporter and reverses transcription-PCR assays revealed that Ihh is up-regulated in embryonic cells upon BMP treatment. It was suggested that the expression of the Ihh gene may be finely regulated by a gradient of BMP concentrations.
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