| Project/Area Number |
16390054
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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 physiology
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| Research Institution | Keio University |
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Principal Investigator |
MATSUZAKI Yumi Keio University, School of Medicine, Associate Professor, 医学部, 助教授 (50338183)
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| Co-Investigator(Kenkyū-buntansha) |
SAWAMOTO Kazuhobu Keio University, School of Medicine, Associate Professor, 医学部, 助教授 (90282350)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,700,000 (Direct Cost: ¥14,700,000)
Fiscal Year 2006: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2005: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 2004: ¥5,400,000 (Direct Cost: ¥5,400,000)
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| Keywords | Notch / Stem cells / Self-renew / Transgenic / Wnt / トランスジェニックマウス / 造血幹細胞 / 神経幹細胞 / レポーター遺伝子 / Notchシグナル / Wntシグナル / 自己複製能 |
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| Research Abstract |
Notch signaling plays various key roles in cell fate determination during CNS development in a context-dependent fashion. However, its precise physiological role and the localization of its target cells remain unclear. To address iris issue, we developed a new reporter system for assessing the RBP-J-mediated activation of Notch signaling target genes in living cells and tissues using a fluorescent protein Venus. Our reporter system revealed. that Notch signaling is selectively activated in neurosphere-initiating multipotent neural stem cells in vitro and in radial glia in the embryonic forebrain in vivo. Furthermore, the activation of Notch signaling occurs during gliogenesis and is required in the early stage of astroglial development. Consistent with these Endings, the persistent activation of Notch signaling inhibits the differentiation of GFAP-positive astrocytes. Thus, the development of our RBP-J-dependent live reporter system, which is activated upon Notch activation, together with a stage-dependent gain-of-function analysis allowed us to gain further insight into the complexity of Notch signaling in mammalian CNS development.
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