| Project/Area Number |
15500228
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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 |
Nerve anatomy/Neuropathology
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| Research Institution | National Institute of Genetics (2004-2005)
The University of Tokyo (2003) |
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Principal Investigator |
SUZUKI Emiko National Institute of Genetics, Structural Biology Center, Associate Professor, 構造遺伝学研究センター, 助教授 (20173891)
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| Co-Investigator(Kenkyū-buntansha) |
KURUSU Mituhiko National Institute of Genetics, Structural Biology Center, Assistant Professor, 構造遺伝学研究センター, 助手 (50413985)
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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 |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | gene / cell-tissue / Drosophila / development / synapse / neuromuscular junction / 神経科学 / シナプス形成 / 電子顕微鏡 / 標的認識 / 免疫細胞化学 / 細胞標識 / 標的認識分子 |
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| Research Abstract |
Establishment of neural networks is based on the target specificity of synaptic connection. The goal of this research project is to elucidate the mechanism that ensures the specific synaptic connectivity. We chose, as a model system, Drosophila embryonic neuromuscular junctions, that constitute relatively simple neural circuits enabling single-cell analyses. By the detailed morphological observation of the stages when an axonal growth cone approaches its target, we found the dynamic interactions of filopodia extending from muscles (myopodia) and neurofiopodia that converge together into a cluster at a definite position for synaptogenesis. The expression of Ezrin-DN in a muscle disturbed cluster formation, leading to abnormal extension of neurites and abortive synaptogenesis. Next, we asked whether the synaptic scaffolding protein PSD-95/Dlg is required in the cluster for proceeding of synaptogenesis. We found that PSD-95/Dlg accumulates in the cluster from the beginning of its formation, and that the expression of Dlg-DN that disturbs endogenous Dig completely blocks the synaptogenesis after the cluster formation. These results indicate that the filopodial clustering plays a pivotal role in synaptogenesis at the right place of a target cell by recruitment of PSD-95/Dlg. Based on these findings, we started a reverse genetic screen for the search of cell-surface proteins involved in the regulation of filopodial clustering that leads to the target-specific synapse formation. By the ectopic expression screening, we have selected about 40 candidate proteins so far. We plan to pursue functional studies on these proteins to elucidate further the mechanism for the synaptogenesis.
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