2005 Fiscal Year Final Research Report Summary
Mechanism for the involvement of the endothelin system in craniofacial and cardiovascular development
| Project/Area Number |
16590659
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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 |
Circulatory organs internal medicine
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| Research Institution | The University of Tokyo |
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Principal Investigator |
KURIHARA Yukiko The University of Tokyo, Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (80345040)
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| Co-Investigator(Kenkyū-buntansha) |
KURIHARA Hiroki The University of Tokyo, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (20221947)
AMANO Tomokazu The University of Tokyo, Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 寄付講座教員(助手相当) (50359634)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Neural crest cell / cardiovascular development / endothelin / endothelin A receptor |
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| Research Abstract |
We have demonstrated that the ET-1(endothelin-1) signal from branchial epithelium to mesenchyme is important to act on the ETAR(ETA receptor) expressed in the neural crest cells. This pathway regulates Dlx5/6 as homeotic gene which is down-steam of its pathway, and plays a role of dorso-ventral patterning in the 1st branchial arch. In other words, we have demonstrated that both dorsal and ventral 1st branchial arch is determined to be upper jaw pattern at the midgestation embryo, but only the ventral portion receives the ET-1-ETAR-Dlx5/6 signal to specify the lower pattern. Then we made the mice in which transgene can be knocked-in into the ETAR gene locus. For this purpose, mutant lox sequences were inserted into the ETAR gene locus to allow Cre recombinase-mediated cassette exchange. The phenotype of ETAR-mutant lox homozygotes are the same as the phenotype of ET-1 or ETAR homozygotes. We then knocked in the LacZ gene into the downstream of ETAR promoter in these mice. Consequently, target cells of the ET-1 signal contributed to branchial arch and cardiovascular development were visualized. These mice enable us to trace the process of cardiovascular development and to analyze of mutual interaction between neural crest cells and other cells. Further knock-in studies are expected to reveal the molecular mechanism underlying branchial arch and cardiovascular development.
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