| Project/Area Number |
10470380
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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 |
Morphological basic dentistry
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| Research Institution | Osaka University |
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Principal Investigator |
KURISU Kojiro Graduate School of Dentistry, Professor, 歯学研究科, 教授 (50028346)
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| Co-Investigator(Kenkyū-buntansha) |
MAKOTO Tabata Graduate School of Dentistry, Research Associate, 歯学研究科, 助手 (20243248)
IWAMOTO Masahiro Graduate School of Dentistry, Assistant Professor, 歯学研究科, 講師 (30223431)
WAKISAKA Satoshi Graduate School of Dentistry, Associate Professor, 歯学研究科, 助教授 (40158598)
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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 |
¥10,200,000 (Direct Cost: ¥10,200,000)
Fiscal Year 2000: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1999: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 1998: ¥4,900,000 (Direct Cost: ¥4,900,000)
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| Keywords | tooth germ / Sonic hedgehog / organ culture / mouse / morphogenesis / development / antisense oligo / differentiation |
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| Research Abstract |
Sonic hedgehog (Shh) is expressed in specific spatio-temporal patterns during odontogenesis, but the specific roles played by this signaling effector are not clear. To address this question, molar tooth germs from E11 and E14 mouse embryos were maintained in organ culture conditions, which allow continuation of their development, in the absence or presence of antisense Shh oligonucleotides. RT-PCR and immunohistological analyses showed that a marked and selective reduction of endogenous Shh expression was caused by antisense oligonucleotide treatment, whereas sense, random or mutated antisense oligomers had no effect. Inhibition of Shh expression in cultured E11 lamina stage tooth germs prevented their progression to the cap stage seen in companion control germs and was accompanied by a sharp reduction of proliferation in both epithelial and mesenchymal cells and down-regulation of hedgehog signal-mediating molecules Patched-1, Patched-2 and Gli-1. Likewise, Shh inhibition in E14 germs led not only to a severe growth retardation but also severe abnormalities in morphogenesis and cytodifferentiation. Control E14 cap stage germs advanced to the bell stage and displayed conspicuous cusps, ameloblasts and odontoblasts, whereas the antisense-treated germs lacked both cusps and differentiated cells. These results show that Shh is an essential factor for normal tooth development is appeared to be required for multiple events, including morphogenesis, cell proliferation and cytodifferentiation.
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