The regulation of tissue morphogenesis by non-coding RNAs
| Project/Area Number |
22590266
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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 |
General medical chemistry
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | noncoding RNA / miR-199a / miR-214 / 形態形成 / 骨形成 / 心筋傷害 / non-coding RNA / micro RNA / 組織形成 / Dnm3os |
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| Research Abstract |
Our research group previously established the Dnm3os gene knockout mice. This gene encodes noncoding RNAs (ncRNAs) including miR-199a and miR-214. Since the mice displayed small body size with hypoplasia of bones and muscular tissues, the author assumed that these noncoding RNAs might regulate tissue morphogenesis. In order to clarify our hypothesis, the author knocked in miR-199a and/or miR-214 in the Dnm3os locus using the recombinase-mediated cassette exchange (RMCE) method. The authorconfirmed that the recovery of the expression of each miRNA among knocked in animals, but the recovery of abnormal phenotypes was observed only when both miRNAs were knocked in. Thus, it became clear that each noncoding RNA contributed to the tissue formation. The author tried to identify the target genes of these ncRNAs in P19 cells by using a unique dual drug selection system, but there seemed no gene displaying remarkable changes in expression. This could reflect the well-known feature of miR s that
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generally suppress the expression level of many genes with a small extent. As miR-199a and miR-214 were reported to change the expression levels in some heart problems, we suspected these genes could be involved in the pathogenesis of heart dysfunctions. Since our research group previously demonstrated that ETAR-positive cells contributed to the formation of heart and vessel systems, the author knocked in these ncRNAs to the ETAR locus using the RMCE method, and compared the histology of hearts with the control animals. Heart injury was induced by the administration of doxorubicin, which was known to cause severe heart injury in high dose in human. As a result, doxorubicin induced myocardial fibrosis in the control animals, but the fibrosis was considerably suppressed in the heart of miR-knocked in animals. These results suggested that miR-199a/214 might contribute to the maintenance of the normal heart function. Additionally, the results obtained here clearly demonstrated that this knock in system was an effective tool to investigate not only the mechanisms oftissue development but also the involvement of genes in disease. Less
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Report
(4 results)
Research Products
(52 results)
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[Journal Article] Preotic neural crest cells contribute to coronary artery smooth muscle involving endothelin signalling2013
Author(s)
Arima Y, Miyagawa-Tomita S, Maeda K, Asai R, Seya D, Minoux m、Rijli FM, 西山 K, Kim KS, Uchijima Y, Ogawa H, Kurihara Y, Kurihara H.
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Journal Title
Nature Communications
Volume: 3
Pages: 1267-1277
Related Report
Peer Reviewed
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[Journal Article] Endothelin receptor type-A expression defines a distinct cardiac subdomain within the heart field, with a later implication of this signaling pathway in chamber myocardium formation2010
Author(s)
Asai R, Kurihara Y, Fujisawa K, Sato T, Kawamura Y, Kokubo H, Tonami K, Nishiyama K, Uchijima Y, Miyagawa-Tomita S, Kurihara H.
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Journal Title
Development
Volume: 137
Pages: 3823-3833
Related Report
Peer Reviewed
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[Journal Article] Establishment of mice expressiong EGFP in the placode-derived inner ear sensory cell lineage and FACS-array analysis focused on the regional specificity of the otocyst2010
Author(s)
Fujimoto C, Ozeki H, Uchijima Y, Suzukawa K, Mitani A, Fukuhara S, nishiyama K, Kurihara Y, Kondo K, Aburatani H, Kaga K, Yamasoba T, Kurihara H.
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Journal Title
Journal of Comparative Neurology
Volume: 18
Pages: 4702-4722
Related Report
Peer Reviewed
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[Presentation] Endothelin type-A receptor expression defines a distinct subpopulation within the first heart field contributing to chamber myocardium2010
Author(s)
Asai R, Kurihara Y, Fujisawa K, Sato T, Kawamura Y, Kokubo H, Tonami K, Nishiyama K, Uchijima Y, Saga Y, Miyagawa-Tomita S, Kurihara H.
Organizer
第33回日本分子生物学会・第 83 回日本 生化学会 合同年会
Place of Presentation
神戸国際展示場(兵庫県神戸市)
Year and Date
2010-12-10
Related Report
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