| Project/Area Number |
12671764
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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 |
Morphological basic dentistry
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
ISEKI Sachiko Tokyo Medical and Dental University, Graduate School, assistant professor, 大学院・医歯学総合研究科, 助手 (80251544)
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| Co-Investigator(Kenkyū-buntansha) |
OTA Masato Tokyo Medical and Dental University, Graduate School, assistant professor, 大学院・医歯学総合研究科, 助手 (70313228)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | skull vault / adenoviral vector / ex-utero surgery / meninges / osteogenesis / Twist / 骨 / 頭蓋骨癒合症 / 線維芽細胞増殖因子受容体 / 増殖と分化 / 骨芽細胞 |
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| Research Abstract |
In order to understand the function of the genes involved in mammalian skull vault development we first investigated the possibility of adenoviral vector-mediated gene expression in vivo. Mouse fetal skull was injected enhanced green fluorescent protein (eGFP) expression vector subcutaneously by ex-utero surgery. There are four layers identified in the developing mouse skull, skin, connective tissue, osteogenic and meningeal layers. In the osteogenic layer each skull bone domain appears at the lateral side of the skull and grow expanding up to the top. Infection specificity in the layers varied according to the stage of the injection. The meningeal layer was preferably infected when the injection was carried out on embryonic day (E)13.5, the osteogenic layer was a major infection site when E14 fetuses were injected. The injection on E14.5 resulted in eGFP expression only in the connective tissue layer.
A transcription factor, Twist, is known to function in maintenance of undifferentiated condition and expressed in undifferentiated mesenchymal cells of the osteogenic layer and ubiquitously in the meningeal layer during the prenatal skull development. We injected the Twist expression vector into either right or left side of a fetal skull. When the infection was achieved in the osteogenic layer bone domain patterning was not affected but the bone on injected side became slightly thinner than that of uninjected side. When Twist was over-expressed in the meningeal layer, however, growth of the bone domains of injected side was inhibited and they stayed at the lateral side of the skull. Expression levels of bone morphogenetic protein 4 and 7, which are normally expressed in the meningeal layer, were severely decreased in Twist over-expressed site. From these results we suggest that a signal from the meningeal layer promotes bone domain growth in the osteogenic layer.
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