| Project/Area Number |
10680695
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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 |
Developmental biology
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| Research Institution | National Institute of Health Sciences |
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Principal Investigator |
SAGA Yumiko National Institute of Health Sciences, 毒性部, 室長 (50221271)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Somitogenesis / Segmentation / Mesp2 knowckout mouse / Anterior-posterior polarity / Notch signaling / Presenilin / Dll1 / 体節の分節化 / cre-lox / Mesp2ノックアウトマウス / 体節中胚葉 / ノックインマウス |
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| Research Abstract |
The somites are the first morphologically distinct segmental units which are formed in pairs on either side of the axial organs in a cranio-caudal order by the successive segmentation of the paraxial mesoderm. Segmented somites are known to be subdivided into anterior and posterior halves that differ in their adhesive properties and gene expression. Notch signaling pathway play an important role to establish metameric pattern during somitogenesis. Notch1 is down-regulated, while expression of Dll1 is expanded in the rostral part of presomitic mesoderm (PSM) of Mesp2 deficient mice, which results in the formation of caudalized vertebra. In contrast, Presenilin-1 (PS1) deficient mice exhibit the reverse phenotype, which is featured by the rostoralized vertebra and the loss of Dll1 expression in the rostral PSM. The compound double deficient mice for Mesp2 and PS1 genes showed exactly same phenotype to MesP2 deficient mice. We took a gene knockin strategy to ask whether the activated Notch1 can rescue segmentation defect observed in Mesp2 and/or PS-1 deficient mice. Activated Notch1 expressed in the Mesp-2- deficient mice strongly induced a downstream gene; Hes-5 but did not rescue the phenotype of Mesp2-deficient mice. However, expression of activated Notch1 in Mesp2/PS-1 double deficient mice resulted in the moderate recovery of the metameric pattern of vertebra, which was accompanied with significant repression of Dll1 expression in the rostral PSM. We propose a model that MesP2 play an important role to suppress Dll1 expression before Dll1activation of PS-1 mediated Notch signaling pathway.
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