2001 Fiscal Year Final Research Report Summary
Molecular machanism of the MFH-1 gene in, the aoortic arch formation, Skeletogenesis and kidney formation
| Project/Area Number |
11694239
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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 |
Molecular biology
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
MIURA Naoyuki Hamamatsu University, School of Medicine, Professor, 医学部, 教授 (40165965)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIDA Nobuaki University of Tokyo, Inst. Medical Science, Professor, 医科学研究所, 教授 (10250341)
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| Project Period (FY) |
1999 – 2001
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| Keywords | MFH-1 / Pax-1 / Endothelin receptor A / Knockout mice / BMp / Heart / Aortic arch / Skeletogenesis |
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| Research Abstract |
In the first year we investigated the relationship between the MFH-1 and Pax1 genes in skeletogenesis. We obtained the results that MFH-1 and Pax1 were expressed in the ventral and lateral areas of sclerotome and that MFH-1 expression is dependent on the notochord. We also investigated that the MFH-1/Pax1 double knockout mice showed more severe defects in cell proliferative ability in the sclerotomal cells than either single knockout mouse did.
These results showed that MFH-1 and Pax1 play a cooperative role in the sclerotome to make vertebraes. In the second year, we investigated the relationship between the MFH-1 and endothelin receptor A (ETA) genes in the aortic arch formation. The results that MFH-1 and ETA were expressed at the similar areas and at similar time and that both knockout mice showed interrupted aortic arch seem likely that there is an upstream-down stream relationship between these two genes. However, the in situ hybridization experiments using the knockout mice indicated that MFH-1 and ETA might act independently in the aortic arch formation. In the last year, we investigated the phenotypes of MFH 1/ETA double knockout mice. We found that the double knockout mice died at the embryonic day of 11.5 day due to heart failure. In the study on the role of MFH-1 gene in the bone differentiation, we found that the MFH-1 gene was expressed strongly just before the bone formation and its expression decreased after the bone was differentiated. Next, we determined whether the MFH-1 gene was induced in response to the implanted beads containing the bone morphogenetic protein (BMP) in the developing mouse limbs. The result showed that the MFH-1 expression was enhanced at a little remote site from the beads. The data together indicate that BMP regulates the MFH-1 gene directly or indirectly in the bone formation of mouse limbs.
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