2005 Fiscal Year Final Research Report Summary
Analysis for vasculogenesis using genetic engineering mice
| Project/Area Number |
15390335
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Embryonic/Neonatal medicine
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
NAKAZAWA Makoto Tokyo Women's Medical University, Faculty of Medicine, Professor, 医学部, 教授 (10075567)
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| Co-Investigator(Kenkyū-buntansha) |
TOMITA Sachiko Tokyo Women's Medical University, Faculty of Medicine, Assistant Professor, 医学部, 助手 (40231451)
KOKUBO Hiroki National Institute of Genetics, Genetic strains research center, Assistant Professor, 系統生物学研究センター, 助手 (10270480)
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| Project Period (FY) |
2003 – 2005
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| Keywords | Notch / heart / angiogenesis / morphogenesis / epithelial-mesenchymal transformation / development / valve |
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| Research Abstract |
Notch signaling pathway regulates cell-fate decisions in metazoans through local cell-cell interactions. Notch signaling influences cell proliferation, differentiation, and is an evolutionarily conserved regulation system ranging from flies to humans. Its dysfunction has resulted in a tremendous variety of developmental defects and adult pathologies. We examined the hairy and enhancer of split-related (hesr) genes, encoding basic helix-loop-helix transcription suppressor factors, which are downstream targets of Notch signaling. Although zebrafish mutants of gridlock, a homolog of mouse hesr2, leads to arterial maturation defects, hesr2 knockout mice lost arterial maturation defects. Instead of that, we showed that the mice had anomalies of cardiac morphology, dysplasia of the atrioventricular valve, a ventricular septal defect, and a secundum atrial septal defect using transthoracic echocardiography on 5-day-old homozygous mice. Double knockout mice for hesr1 and hesr2 showed vascular anomalies that are strikingly similar to that of the zebrafish gridlock mutants. Hesr1 and hesr2 function synergistically in epithelial- mesenchymal transformation during atrioventricular valve formation and maintenance of trabecular cells in the ventricles, and in arterial-venous differentiation of blood vessels.
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Research Products
(14 results)
