2001 Fiscal Year Final Research Report Summary
Upstream signals of left-bide specific nodal expression in the lateral plate mesoderm
| Project/Area Number |
12680716
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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 | Osaka University |
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Principal Investigator |
SAIJOH Yukio CELLULAR BIOLOGY, Osaka University, ASSISTANT, 細胞生体工学センター, 助手 (20260333)
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| Project Period (FY) |
2000 – 2001
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| Keywords | nodal / transcriptional regulation / left-right asymmetry / transgenic mouse / knockout mouse |
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| Research Abstract |
I focused on transcriptional regulation of nodal in order to understand the left-right determination pathway in the lateral plate mesoderm. ASE is a left side enhancer of nodal and lefty2 in the lateral plate mesoderm. Nodal gene is also regulated by another enhancer, the left side specific enhancer LSE. Using transgenic technique, I identified this enhancer activity in a 300b region 5 kb upstream of nodal gene. Deletion analysis of this region in detail revealed three independent regions essential for LSE activity. These regions did not contain FoxH1 binding sequences which regulate ASE of nodal and lefty2. Therefore LSE was regulated by at last three different signals other than FoxH1.
In order to study the function of LSE in the left-side specific expression of nodal, LSE deleted knockout mice were generated by using the Cre-loxP system. The LSE region was replaced by a PGK-neo gene inserted between loxP sequences, and subsequently PGK-neo gene was excised by Cre recombinase. Postnatal development of the mutants was slightly delayed compared with wild type mice.
Since some mutant homozygotes showed atrial septum defects left-right information was affected by the deletion of LSE. Therefore, expression patterns of left-side expressed genes such as nodal, lefties and Pitx2 were examined at 8 days post coitum. These genes were expressed in the mutant embryos. However, the beginning of the expression of nodal was delayed for about 1 somite period in mutant embryos.
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Research Products
(12 results)
