2004 Fiscal Year Final Research Report Summary
Molecular mechanisms that specify the cardiac cell lineage
| Project/Area Number |
15590738
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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 | Kyoto University |
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Principal Investigator |
TANAKA Makoto Kyoto University, Graduate school of Medicine, Associate Professor, 医学研究科, 助教授 (00271007)
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| Project Period (FY) |
2003 – 2004
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| Keywords | cardiac myocyte / development / differentiation / regeneration |
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| Research Abstract |
In this study, we investigated molecular mechanisms that specify the cardiac cell lineage by analyzing enhancers of Nkx2.5, a cardiac specific transcription factor. We isolated BAC clones that cover 60kb of upstream sequence of Nkx2.5 and generated approximately 70 reporter constructs containing various length of the upstream sequence. We measured luciferase activity of each construct in primary culture of rat neonatal cardiac myoctyes and identified 6 regions exhibiting significantly high luciferase activities. We subcloned these 6 DNA fragments into a LacZ reporter vector and generated transgenic mice. Out of the 6 fragments, 3 fragments showed enhancer activities in vivo. Particularly, a DNA fragment between 5.2 and 6.4kb upstream of Nkx2.5 exhibited strong activity in cardiac myocytes from the cardiac crescent to the straight heart tube. This DNA fragment contained tandem Smad binding sites and deletion of the Smad binding sites almost abolished the enhancer activity in cultured cardiac myocytes. This result suggested that the Smad signaling pathway was required for expression of Nkx2.5 at early stages of cardiac development and may play a critical role in the specification of the cardiac cell lineage. We are now trying to confirm this result in vivo using transgenic approach. In this fragment, we also found another region having high reporter activity in vitro. Since this region did not contain known cis-acting elements, we are trying to isolate binding proteins using yeast one-hybrid system.
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[Journal Article] Expression of the novel Snai-related zinc-finger transcription factor gene Smuc during mouse development.2005
Author(s)
Zhuge X, Kataoka H, Tanaka M, Murayama T, Kawamoto T, Sano H, Togi K, Yamauchi R, Ueda Y, Xu Y, Nishikawa S, Kita T, Yokode M
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Journal Title
Int J Mol Med. 15
Pages: 945-948
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Up-regulation of SR-PSOX/CXCL16 and recruitment of CD8^+ T cells in cardiac valves during inflammatory valvular heart disease.2004
Author(s)
Yamauchi R, Tanaka M, Kume N, Minami M, Kawamoto T, Togi K, Shimaoka T, Takahashi S, Yamaguchi J, Nishina T, Kitaichi M, Komeda M, Manabe T, Yonehara S, Kita T.
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Journal Title
Arterioscler Thromb Vasc Biol 24
Pages: 282-287
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Nkx2.5 mutation causes anatomic hypoplasia of the cardiac conduction system.2004
Author(s)
Jay PY, Harris BS, Maguire CT, Buerger A, Wakimoto H, Tanaka M, Kuperschmidt S, Roden DM, Schultheiss TM, O'Brien TX, Gourdie RG, Berul CI, Izumo S.
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Journal Title
J.Clin.Invest. 113
Pages: 1130-1137
Description
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