| Project/Area Number |
06671805
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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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 |
YAMASHITA Noriko Tokyo Medical and Dental Unibersity, Faculty of Dentistry, Research Associate, 歯学部, 助手 (00220343)
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| Co-Investigator(Kenkyū-buntansha) |
NINOMIYA Youichirou Tokyo Medical and Dental University, Faculty of Dentistry, Research Associate, 歯学部, 助手 (90237777)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1994: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | Craniofacial malformation / Cranial neural crest cells / retinoic acid / Mammalian whole embryo culture / Rat / Mouse / Cranial nerves / CRABP-I / CRABP-I / ラット胚 / 鰓弓(咽頭弓) / transformation / 顎顔面形態異常 |
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| Research Abstract |
Retinoic acid (RA), a natural metabolite of vitamin A,is essential for normal mammalian development. However, embryos exhibit anomalies also by excess vitamin A and other natural and synthesized retinoids including RA.Craniofacial malformations experimentally induced with retinoids in laboratory animals are regarded as models for human congenital anomalies such as Treacher-Collins and Di George syndromes. Since cranial neural crest cells play important roles in development of head and face, here we have established in vitro conditions which reproducibly induce typical phenotypes of craniofacial abnormalities and examined behavior of the crest cells.
9.0 day and 9.5 day rat embryos were treated in vitro with all-trans-RA for 6 hours and further cultured up to the stage corresponding to 11.5 day in vivo embryos. The former treatment induced posteriorization in the CNS and pharyngeal arches, while the latter treatment resulted in fusion of the first and second arches as well as that of the trigeminal and acousticofacial ganglia. Interestingly, DiI labeling study revealed that crest cells derived from the anterior and preotic hindbrain do not mix within the fused arch. It supports the idea that differential identities of the crest cell populations are still maintained. In contrast, crest cells from the anterior hindbrain ectopically migrate into the second arch in cultured rat embryos treated at 9.0day, suggesting that RA affected not only the identity of the hindbrain neuroectoderm but also that of the crest cells derived from the hindbrain. Thus, RA affected migration of crest cells and features of cranial nerves in a stage-dependent manner. Such stage dependency in RA's effects was also observed at the molecular level since the distribution pattern of CRABP-I protein was unchanged in the late-stage treatment but drastically altered in the early-stage treatment.
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