| Project/Area Number |
15590900
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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 |
Neurology
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| Research Institution | Kagoshima University |
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Principal Investigator |
UMEHARA Fujio Kagoshima University, Graduate School of Medical and Dental Sciences, Assistant Professor, 大学院・医歯学総合研究科, 講師 (20271140)
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| Co-Investigator(Kenkyū-buntansha) |
TATE Genshu Showa University, Faculty of Medicine, Professor, 医学部, 講師 (10216997)
ARIMURA Kimiyoshi Kagoshima University, Graduate School of Medical and Dental Sciences, Associate Professor, 大学院・医歯学総合研究科, 助教授 (20159510)
OSAME Mitsuhiro Kagoshima University, Graduate School of Medical and Dental Sciences, Professor, 大学院・医歯学総合研究科, 教授 (10041435)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | Desert hedgehog / peripheral nervous system / Schwann cell / Patched / ノックアウト マウス / 神経再生 / 行動解析 / 性分化異常症 / 遺伝性抹消神経障害 |
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| Research Abstract |
Role of Desert hedgehog signalin pathway in the peripheral nervous system
The hedgehog(Hh) family of secreted ligands has critical role in a variety of developmental processes in insects and vertebrates. Three homologs of Hh ; Sonic, Indian and Desert (Dhh) hedgehog have been described in mammals. Dhh signaling pathway is involved in the development of peripheral nerves. Hh signaling is mediated by a multicomponent receptor complex involving two transmembrane proteins, Patched(Ptc) and Smoothened(Smo). We found that both dhh and patched 2(ptc2) mRNA were expressed in adult mouse peripheral nerves but ptc1 mRNA was undetectable. Using RT-PCR in purified cultures of mouse Schwann cells and fibroblasts, we have found ptc2 mRNA in Schwann cells, and at much lower levels, in the fibroblasts. By immunohistochemistry, Ptc2 protein was seen in unmyelinated nerve fibers. After sciatic nerve crush injury, wild type(WT) and dhh-null nerves were analyzed morphologically at different time points and expression of dhh mRNA and related receptors (Ptc1, Ptc2, and Smo) was also measured by RT-PCR in WT mice. In dhh-null mice, degeneration of myelinated fibers was more severe than in WT mice. Furthermore, in regenerated nerves of dhh-null mice, minifascicular formation was even more extensive in than in dhh-null intact nerves. Dhh and ptc2 mRNA expression showed a marked decline during the degenerating phase after injury in WT mice followed by a slow increase in the regenerating phase. The ptc1 mRNA was undetectable in both injured and control nerves and the smo mRNA levels did not change after injury. These results suggest that the Dhh-Ptc2 signaling pathway may be involved in the maintenance of adult nerves and degeneration and regeneration process after injury.
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