| Project/Area Number |
13308044
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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 |
Neurochemistry/Neuropharmacology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
MIKOSHIBA Katsuhiko Institute of Medical Science, Professor, 医科学研究所, 教授 (30051840)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥45,630,000 (Direct Cost: ¥35,100,000、Indirect Cost: ¥10,530,000)
Fiscal Year 2002: ¥20,670,000 (Direct Cost: ¥15,900,000、Indirect Cost: ¥4,770,000)
Fiscal Year 2001: ¥24,960,000 (Direct Cost: ¥19,200,000、Indirect Cost: ¥5,760,000)
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| Keywords | dorsoventral axis formation / IP_3 receptor / GSK3β / NF-AT / Calcium / Wnt singnaling / カルシウムシグナリング / 神経可塑性 / 脳の発生・分化 / シナプス / 長期増強 / 長期抑圧 / IP_3レセプター欠損マウス |
|---|
| Research Abstract |
The involvement of IP_3-Ca^<2+> signaling in dorsoventral axis formation in Xenopus embryo has been proposed, but the immediate target of free Ca^<2+> is not well understood. The secreted Wnt protein family comprises two functional groups, canonical Wnt and Wnt/Ca^<2+> pathways. Despite the finding that the Wnt/Ca^<2+> pathway interfered with the canonical Wnt pathway, the underlying molecular mechanism is poorly understood. We cloned the cDNA encoding Xenopus homolog of the nuclear factor of activated T-cell (XNF-AT). Gain-of-function XNF-AT mutant (CA XNF-AT) inhibited anterior development of the primary axis as well as Xwnt8-induced ectopic dorsal axis. Loss-of-function XNF-AT mutant (DN XNF-AT) induced an ectopic dorsal axis and expression of the canonical Wnt signaling target molecules, siamois and Xnr3. Xwnt5A induced translocation of XNF-AT from the cytosol to the nucleus. These data strongly suggest that XNF-AT functions as a downstream target of Wnt/Ca^<2+> and IP_3-Ca^<2+> pathways and plays an essential role in mediating ventral signals in the Xenopus embryo by suppressing the canonical Wnt pathway.
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