| Project/Area Number |
14380365
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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 |
Neuroscience in general
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| Research Institution | Nagaoka University of Technology |
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Principal Investigator |
WATANABE Kazutada Nagaoka University of Technology, Department of Bio Engineering, Professor, 工学部, 教授 (70114717)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMODA Yasushi Nagaoka University of Technology, Department of Bio Engineering, Assistant Professor, 工学部, 助手 (00291154)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥14,000,000 (Direct Cost: ¥14,000,000)
Fiscal Year 2004: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2003: ¥5,200,000 (Direct Cost: ¥5,200,000)
Fiscal Year 2002: ¥5,800,000 (Direct Cost: ¥5,800,000)
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| Keywords | contactin / Notch / oligodendrocyte / Deltex1 / MAG / Myelin / Notch1 / ミエリン化 / OLN-93細胞 |
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| Research Abstract |
Contactin and NB-3 are neural adhesion molecules which belongs to contactin subgroup of the immunoglobulin superfamily. Recent studies revealed that subgroup molecules of cotactin and TAG-1 play essential roles in the formation of myelination. On the other hand, oligodendrocyte maturation is known to be suppressed by the interaction between Jagged1 on neuronal axon and Notch on the oligodendrocyte precursor cell (OPC). In the suppression, intracellular domain of Notch translocates to the nucleus to associate RBP-J and upregulates Hes1 expression. Here, we identified that contactin and NB-3 are functional ligands of Notch to promote the oligodendrocyte. Maturation. Interaction of Notch with contactin or NB-3 triggers the nuclear translocation of Notch intracellular domain and upregulates MAG and CNPase in the oligodendrocyte cell line OLN-93. The upregulation of these molecules was blocked by dominant negative constructs of Notch 1, Notch2 and Deltex, but not by dominant-negative RBP-J. In addition, antisense oligonucleotides for Hes1 did not upregulated the MAG or CNPase in the OLN-93. Coculture of OLN-93 cells with contactin-cDNA transfected CHO cells stops the OLN-93 processes at the CHO cells to elaborate flattened cytoplasmic sheets that envelope the cell bodies. Treatment of OPCs with contactin induced the expression of CNPase and differentiated to become matured oligodendrocytes. Thus, contactin and NB-3 differentiate OPCs to the matured oligodendrcytes through Notch signaling via Deltex1.
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