| Project/Area Number |
10680691
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Fujjita Health University |
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Principal Investigator |
KADOKAWA Yuzo Institute of Comprehensive Medical Science, Assistant Professor, 総合医科学研究所, 講師 (00261199)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Masahiko Institute of Comprehensive Medical Science, Lecturer, 総合医科学研究所, 講師 (60267953)
HAMADA Yosio National Institute for Basic Biology, Assistant Professor, 基礎生物学研究所, 助手 (10132739)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥2,800,000 (Direct Cost: ¥2,800,000)
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| Keywords | North2 / gene targeting / glial cell / dumeric mouse / roof plate / sortiry out / wut-1 / Mash1 / Notch 2 / ノックアウトマウス / アポトーシス |
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| Research Abstract |
1. Norch2 expression negatively correlates with glial differentiation in the postnatal mouse brain
Norch2 was expressed by Bergmann glia in the cerebellm, radia glia in the hippocampus, and some astrocytes in both regions.,
Immunohistochemical examination revealed that the expression level of Notch2 is higher in immature glial cells than matured glial cells. In addition, Notch 2 expression correlated with the incorporation of BrdU both in vivo and in vitro. We also showed that ectopic expression of cytoplasmid region of Notch 2 gene, which is known to constitutively activate Notch signalling pathway, up-regulated the incorporation of BrdU in glial cells.
2. Notch2 is required for the formation of the roof plate of the diencephalon and mesencephalon
Targeted disruption of mouse Notch2 gene in mice results in embryonic lethality around E10.5 with widespread cell death. In order to study Notch2 function in development beyond the embryonic lethal stage, we produced chimeras between Notch2ィイD1m
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/mィエD1 and wild-type mice. While chimeric mice showed mosaicism inevery tissue studied so far at E9.5, Notch2ィイD1m/mィエD1 cells failed to contribute to formation of the roof plate of the diencephalon and messencephalon, where Notch2 is normally expressed at high levels. Notch2ィイD1+/mィエD1cells were also preferentially excluded from the roof plate in chimeras with wild type. These results indicate that Notch2 is necessary in a dose-dependent manner for morphogenesis of the roof plate and suggest that cell rearrangement is involved in this process.
We also showed that Wnt-"I" snf Mash expression patterns at the roof plate were disorganized in Notch2ィイD1m/mィエD1 embryos. To clarify the Notch2 signalling pathway in the roof plate, we introduced constitutive active form of Notch2 gene into the mesencephalon of mouse embryos at E9.5 and cultured for one day in vitro. The expression of Wnt-"I" was repressed by the ectopically introduced Notch2 gene at the roof plate. We are now trying to reveal the Notch2 signalling pathway in the roof plate and the function of it in the morophogenesis of the brain. Less
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