The role of Hand genes for the cardiac ventricular developinent and regionalization
| Project/Area Number |
18591168
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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 |
Pediatrics
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| Research Institution | Keio University |
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Principal Investigator |
MAEDA Jun Keio University, School of Medicine, Instructor (00255506)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAGISHI Hiroyuki Keio University, School of Medicine, Assistant Professor (40255500)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Hand genes / ventricular chamber development / Pharyngeal arch development |
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| Research Abstract |
Hand genes (Hand1/eHand and Hand2/dHand) encode critical transcription factors required for cardiovascular and pharyngeal development. Hand2 is expressed predominantly in developing right ventricle, whereas Hand1 is restricted in left ventricle. Both Hand genes direct overlapping expression in pharyngeal arch mesenchyme. Hand1 null cardiac-specific null mice display defects in left ventricle and endocardial cushion. Hand2 null (Hand2^<-/->) mice display severe hypoplasia of right ventricle and die at embryonic day (E) 10.5 due to the heart failure resulting in degenerative pharyngeal arch and limb buds. To delineate the genetic redundancy and regional function of Hand genes in murine development we genetically engineered Hand2^<Hand1/Hand1> mice where Hand2 gene was replaced by the Hand1 cDNA using homologous recombination so that Hand1 was driven under control of endogenous Hand2 promoter. We also generated Hand2^<Hand1/-> mice from mating of Hand2^<Hand1/+> mice with Hand2^<+/-> mice. Our observation reveled that Hand2^<Hand1/Hand1>mice had hypoplastic right ventricle and preserved pharyngeal arch and survived until E13.5. This phenotype was milder than that of Hand2^<-/->or Hand2^<Hand1/-> mice. These findings suggest that Hand1 could partially compensate the function of Hand2 in ventricular and pharyngeal arch formations in a dose dependent fashion during development. These results indicate that in mammalian cardiac ventricles and pharyngeal arch, Hand genes may have common function and partial genetic redundancy. The complementally expression of Hand genes may be essential for regionalization of right and left ventricles.
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Report
(3 results)
Research Products
(15 results)
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[Journal Article] III-K. cardiovascular Disease/Congenital Heart Defect Ventricular Septal Defect. Lectures Child-health and Developmental Medicine2008
Author(s)
Jun, Maeda, Hiroyuki, Yamagishi, Tsutomu, Saji, Osamu, Arisaka, Makiko, Oosawa, Naomi, Kondo, Tsukasa, Takemura
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Journal Title
Medical View
Pages: 469-471
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Chapter 9. Hand genes in the mammalian heart chamber formation. Future Aspects of Medical Sciences and Education 2nd IREIIMS Open Symposium2007
Author(s)
Jun, Maeda, Hiroyuki, Yamagishi, Takatoshi, Tsuchihashi, Eric N, Olson, Deepak, Srivastava, Nadal-Ginard, Bernardo, Kintomo, Takakura
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Journal Title
International Research and Educational Institute for Integrated Medical Sciences (IREIIMS), p.29-31, Tokyo Women's Medical University
Pages: 29-31
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] Redundant and tissue-specific roles of Hand genes in heart, limbs, and cranial development2007
Author(s)
Jun, Maeda, Takatoshi, Tsuchihashi, Chihiro, Yamagishi, Deepak, Srivastava, Hiroyuki, Yamagishi
Organizer
3rd Congress of Asian Society for Pediatric Research
Place of Presentation
Tokyo, Japan
Year and Date
2007-07-10
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] Hand genes in the mammalian heart formation2007
Author(s)
Jun, Maeda, Takatoshi, Tsuchihashi, Hiroyuki, Yamagishi, Eric N, Olson, Deepak, Srivastava
Organizer
American Heart Association Scientific Sessions 2007
Place of Presentation
Orland, Florida, USA
Year and Date
2007-06-11
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] Hand genes in the mammalian heart chamber formation2006
Author(s)
Jun, Maeda, Hiroyuki, Yamagishi, Takatoshi, Tsuchihashi, Eric, N, Olson, Deepak, Srivastava
Organizer
2nd International Research and Educational Institute for Integrated Medical Sciences(IREIIMS)open symposium Future Aspects of Medical Sciences and Education "Challenge of Integrated Medical Sciences"
Place of Presentation
Tokyo, Japan
Year and Date
2006-03-12
Description
「研究成果報告書概要(欧文)」より
Related Report
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