| Project/Area Number |
11694227
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Developmental biology
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| Research Institution | Natiomal Institute of Genetics (2000-2001)
National Institute of Health Sciences (1999) |
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Principal Investigator |
SAGA Yumiko Natiomal Institute of Genetics, Professor, 系統生物研究センター, 教授 (50221271)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAGI Atsuya Natiomal Institute of Health sciences,Senior Research Associate, 毒性部, 主任研究官 (00179417)
北嶋 聡 国立医薬品食品衛生研究所, 毒性部, 研究員 (30270622)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥19,700,000 (Direct Cost: ¥17,600,000、Indirect Cost: ¥2,100,000)
Fiscal Year 2001: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Fiscal Year 2000: ¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1999: ¥3,600,000 (Direct Cost: ¥3,600,000)
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| Keywords | somitogenesis / Mesp2 / 読めない / rostrocaudal polarity / knockout mice / myogenesis / paraxis / vetebral column / 筋分化 / Mesp2ノックアウトマウス / プレセニリン / 分節化 / 上皮化 / パラキシス |
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| Research Abstract |
Elaborate metamerism in vertebrate somitogenesis is based on precise stripe pattern of gene expression, representing establishment of rostro-caudal polarity in the presomitic rnesoderm (PSM). Previously we have reported that expression pattern of a Notch ligand, Dill is well correlated with the rostro-caudal polarity, and a transcription factor Mesp2 and a Notch signal mediator Presenilinl differentially regulate Dill expression to specify rostral or caudal half of a somite. Here we examined in detail changes in expression domain of Mesp2 and Dill, and describe that the process of formation of the rostral and caudal halves is rather complex, i. e. narrowing stripes of Mesp2 and Dill are still overlapped and only finally separated to each other. We also analyzed genetic interaction between Dill and Mesp2, and show that Dill induces expression of Dill itself and Mesp2, whereas Mesp2 suppresses expression of Dill. This cascade also explains expansion of Mesp2-LacZ in the absence of Mesp2,
… More
and is supported by the phenotype of Dill/ Mesp2 double mutant embryo, which lacks expansion of Mesp2-LacZ. Analysis of the rostro-caudal polarity in the Dill/ Mesp2 double mutant revealed that Mesp2 suppresses expression of Uncx4.1, a caudal half marker gene, in both Dill-dependent and independent manner. Thus, the positive and negative feedback loop composed of Dill and Mesp2 appears to be critical for the establishment of the segmental pattern of gene expression at the rostral PSM. In addition, we found that Mesp2 and Paraxis act synergistically to generate the vertebral column. In Mesp2/Paraxis double mutants, the axial skeleton and ribs were severely malformed. Although partial cartilaginous vertebrae are present in the all-axial levels, they are fused and almost no ossification was observed caudal to the pelvis. However, so far we have not observed the synergistic primary defect in the expression of genes implicated for sclerotomal development (origin of axial skeleton). In contrast, synergistic defect was evident in the myotome, because myotomal marker Myf-5 was clearly downregulated in the double mutant mouse. These results indicate that myotomal defects may cause sclerotomal abnormality resulting in the defective development of axial skeleton Less
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