| Project/Area Number |
10044247
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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 |
Cell biology
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| Research Institution | Kumamoto University (2000)
Tokyo Medical and Dental University (1998-1999) |
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Principal Investigator |
TAGA Tetsuya Kumamoto University, Institute of Molecular Embryology and Genetics, Professor, 発生医学研究センター, 教授 (40192629)
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| Co-Investigator(Kenkyū-buntansha) |
NOBUHISA Ikuo Kumamoto University, Institute of Molecular Embryology and Genetics, Research Associate, 発生医学研究センター, 助手
NAKASHIMA Kinichi Kumamoto University, Institute of Molecular Embryology and Genetics, Associate Professor, 発生医学研究センター, 助教授 (80302892)
オースチン G.スミス エジンバラ大学, ゲノム研究センター, 所長
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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 |
¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 2000: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1999: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1998: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | astrocyte / cytokine / differentiation / gp130 / neural stem cell / neurons / STAT3 / transcription factor / AGM領域 / gp130 / 分化 / アストロサイト / STAT3 / 胚性幹細胞 / ES細胞 |
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| Research Abstract |
Development of multicellular organs is regulated by various external signals and intrinsic cues. This project is amied to understand molecular regulation of organ development, in particular brain development, by focusing on cytokine signaling. The interleukin-6(IL-6) family of cytokines, i.e. IL-6, IL-11, leukemia inhibitory factor(LIF), ciliary neurotrophic factor(CNTF), oncostatin M(OSM), and cardiotrophin-1(CT-1), share gp130 as a receptor component critical for signal transduction. We have found that signals from gp130 and bone morphogenetic protein(BMP) receptors act in synergy on fetal brain neural progenitor cells to induce astrocyte differentiation. For instance, LIF and BMP2 synergistically induce astrocytes in cultured neuroepithelial cells. The molecular basis proposed by us is that respective downstream transcription factors, STAT3 and Smads, form a complex bridged by a transcriptional coactivator p300. Another finding is that BMP2 inhibits neurogenesis from neural progenitor cells by upregulating expression of negative helix-loop-helix(HLH) factors, Id1, Id3 and Hes-5, which are capable of inhibiting transcriptional activity of neurogenic HLH transcription factors, Mash1 and Neurogenin. We have also identified several novel genes that are likely to regulate brain development : (1)Tbr-2 is a new member of the T-box containing gene family which is expressed predominantly expressed in the developing brain. (2)Lhx6.1 is a molecule very close to Lhx6 and shows obvious expression in olfactory bulb, medial ganglionic eminenee, arcuate nucleus in mouse fetal brain. (3)NDRP is a novel molecule expressed predominantly in developing retina, olfactory bulb and dorsal root ganglion.
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