Analysis of molecular mechanism in cardiovasculogenesis by Notch signaling gene manipulation
| Project/Area Number |
15590175
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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 anatomy (including Histology/Embryology)
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
TOMIMATSU Hirofumi Tokyo Women's Medical University, Department of Pediatric Cardiology, Assistant Professor, 医学部, 助手 (90197939)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAGAWA Sachiko (TOMITA Sachiko) Tokyo Women's Medical University, Department of Pediatric Cardiology, Assistant Professor, 医学部, 助手 (40231451)
KOKUBO Hiroki National Institute or Genetics, Division of Mammalian Development, Assistant Professor, 系統生物研究センター, 助手 (10270480)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2003: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | Notch signaling / cardiovasculogenesis / hesr genes / development / mouse / 心血管 / 形態形成 |
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| Research Abstract |
Notch signaling is required for multiple aspects of cardiovascular development, including arterial-venous differentiation, septation and cushion formation. Despite recognition of the importance of the Notch pathway in normal cardiovascular development, the proximate downstream effectors are not yet known. Likely candidate effectors are members of the hairy and enhancer of split related (hesr) family of basic helix-loop-helix(bHLH) transcription factors. However, mutational analysis of individual hesr genes has so far failed to elucidate their role in all Notch-mediated cardiovascular signaling events. An example of this is evident for mutants of gridlock, the zebrafish counterpart of mouse hesr2, which have vascular defects, whereas mouse hesr2 mutants have only cardiac defects. One possible explanation for these differences could be functional redundancy between hesrfamily members.
We report that mice lacking the hesr1 gene are viable and fertile, whereas knockout mouse of both hesr1 and hesr2 is embryonic lethal at 11.5 days postcoitum(dpc). Hesr1/2 double mutants show most of the known cardiovascular phenolypes of disrupted Notch pathway mutants including defects in arterial-venous specification, septation and cushion formation. Taken together, our results demonstrate a requirment for hesr1 and hesr2 in mediating Notch signaling in the developing cardiac and vascular systems.
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Report
(3 results)
Research Products
(18 results)
