| Project/Area Number |
08680822
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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 | Kochi Medical School |
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Principal Investigator |
MIMA Tatsuo Kochi Medical School Research Associate, 医学部・附属病院, 助手 (30192363)
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| Co-Investigator(Kenkyū-buntansha) |
MORI Takahisa Kochi Medical School Research Associate, 医学部・附属病院, 助手 (20230071)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1997: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1996: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | fibroblast growth factor / signal transduction / neuronal differentiation / cell proliferation / retrovirus / gene transfer / chick embryo / optic tectum / ニワトリ / 発生 |
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| Research Abstract |
Although it has been believed that FGF signaling induces neuronal differentiation, the results have mainly derived from in vitro studies. We examined in vivo roles of FGF signaling in neuronal differentiation using a retrovirus-mediated gene transfer method. We prepared a set of replication-defective retroviruses which permit both to mark infected cells and to regulate FGF signaling. For upregulation of FGF signaling, we made two types of viruses overexpressing a ligand (FGF1) or a receptor (FGFR1). For downregulation, we designed viruses to overexpress a truncated mutant of FGFR1 which lacks intracellular tyrosine kinase domain serving as a competitive inhibitor. LacZ gene was also inserted to each virus for expressing beta-galactosidase as a marker. Each virus was microinjected into the neural tube on the embryonic day 3, and analyzed the embryos on embryonic day 7. Upregulated FGF signaling inhibited cell migration to the marginal zone and only a few cells were differentiated into neurons. The colony shape was shortened in radial direction and its adjacent ventricular surface was concaved. When many colonies were infected with FGF-overexpressing viruses, hydrocephalus-like thin cortex was generated. In contrast, downregulated FGF signaling suppressed cell proliferation. In conclusion, upregulation of FGF signaling, contrary to the conventional wisdom, inhibited neuronal differentiation in the optic tectum of the chick embryo.
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