| Project/Area Number |
10480228
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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 | National Institute for Physiological Sciences |
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Principal Investigator |
IKENAKA Kazuhiro National Institute for Physiological Sciences, Professor, 生理学研究所, 教授 (00144527)
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| Co-Investigator(Kenkyū-buntansha) |
IWASAKI Yasuno National Institute for Physiological Sciences, Research Associate, 生理学研究所, 助手 (40311196)
NAKAHIRA Kensuke Saitama Medical School Department of Physiology, Lecturer, 第二生理学教室, 講師 (10260043)
BABA Hiroko Tokyo University of Pharmacy and Life Sciences, Professor, 薬学部, 教授 (40271499)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥12,000,000 (Direct Cost: ¥12,000,000)
Fiscal Year 2000: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1999: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1998: ¥5,400,000 (Direct Cost: ¥5,400,000)
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| Keywords | oligodendrocyte / astrocyte / PDGFα receptor / myelin proteolipid protein / Cystatin C / グリア細胞 / 細胞系譜 / Glial Cell Missing / アストロサイト / レトロウィルス / GFAP / GLAST |
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| Research Abstract |
We studied cell lineage of various glial cells and the mechanism underlying their differentiation. We used PLP, PDGFα receptor and O4 to mark cells of oligodendrocyte (OL) lineage, and BrdU incorporation to label proliferating cells. Even at a very early embryonic period PLP- or O4- positive cells were not dividing in the mouse hind brain or spinal cord while PDGFR α -positive cells were. On the other hand in the neonatal cerebral cortex PLP-positive cells were dividing and can therefore be considered as an OL progenitor. However, there were no overlaps between PLP-and PDGFR α -positive cells, indicating that there are two OL lineage in the mouse cerebral cortex.
We developed a flat whole mount culture, in which the dorsal midline of hind brain to cervical spinal cord region is cut open and cultured, preserving most of the three dimensional architecture. Using this system we showed that the development of OL is inhibited by the factor present in the dorsal portion of the spinal cord and that this factor is not BMPs. This might expain why OL can develop from such a restricted region of ventral spinal cord.
We isolated an endogenous cystein protease inhibitor, Cystatin C (CysC), as an a strocyte-inducing factor. When CysC was added into the culture medium of prima ry embryonic brain cell culture, it increased the number of astrocyte. This activi ty was mimicked by the addition of a synthetic cystein protease inhibitor, E64. I n the neurosphere assay the effect was more prominent, indicating that cell-cell i nteraction is important in exerting CysC effects. Thus, astrocyte development is regulated by cystein proteases and inhibition of their activity induces astrocyte dif ferentiation.
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