| Project/Area Number |
15207016
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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 |
Developmental biology
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| Research Institution | Tohoku University |
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Principal Investigator |
NAKAMURA Harukazu Tohoku University, Department of Molecular Neurobiology, Graduate School of Life Sciences, Professor, 大学院・生命科学研究科, 教授 (90079690)
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| Co-Investigator(Kenkyū-buntansha) |
FUNAHASHI Junichi Tohoku University, Department of Molecular Neurobiology, Institute of Development, Aging & Cancer, Associate Professor, 加齢医学研究科, 助教授 (00270827)
WATANABE Yuji Tohoku University, Department of Molecular Neurobiology, Graduate School of Life Sciences, Assistant professor, 大学院・生命科学研究科, 助手 (80301042)
片平 立矢 東北大学, 大学院・生命科学研究科, 日本学術振興会特別研究員(PD)
佐藤 達也 東北大学, 大学院・生命科学研究科, 日本学術振興会特別研究員
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥50,310,000 (Direct Cost: ¥38,700,000、Indirect Cost: ¥11,610,000)
Fiscal Year 2005: ¥14,690,000 (Direct Cost: ¥11,300,000、Indirect Cost: ¥3,390,000)
Fiscal Year 2004: ¥14,690,000 (Direct Cost: ¥11,300,000、Indirect Cost: ¥3,390,000)
Fiscal Year 2003: ¥20,930,000 (Direct Cost: ¥16,100,000、Indirect Cost: ¥4,830,000)
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| Keywords | chick embryo / cerebellum / Fgf8-Ras-ERK signaling cascade / organizer / Sprouty2 / regulation / misexpression / tectum / 峡部 / Fgf8 / Ras-ERKシグナル伝達系 / エレクトロポレーション / Ras-ERKシグナル経路 / siRNA / 遺伝子発現阻害 |
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| Research Abstract |
The isthmus works as an organizer, and Fgf8 mimics the organizing activity. The isthmic organizer plays a role for the development of the tectum and the cerebellum in the mesencephalon and in the metencephalon, respectively. It was previously shown that strong Fgf8 signal induces cerebellar differentiation. In the present study, we have shown that strong Fgf8 signal activates Ras-ERK signaling cascade. If we shut down this signaling cascade by misexpression of dominant negative form of Ras (DN-Ras), y electroporation the fate of the metencephalon changes to the mesencephalon, and the tectum differentiates in place of the cerebellum. Then, we focused on Sprouty2. Sprouty2 is expressed overlapping to Fgf8, but was indicated as a negative regulator of Ras-ERK signaling cascade. As indicated, Sprouty2 expression was induced rapidly by Fgf8, that is, 2 hours after electroporation of Fgf8 expression vector, and repressed ERK activation. Misexpression of Sprouty2 exerted similar results as that of DN-Ras, that is, fate change of the metencephalon to the mesencephalon. On the other hand, misexpression of dominant negative form of Sprouty2 resulted in anterior shift of the mes-metencephalic boundary. The results indicate the need of fine regulation of Ras-ERK signaling.
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