| Project/Area Number |
18390091
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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 |
General medical chemistry
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| Research Institution | Kyushu University (2007)
National Institute for Basic Biology (2006) |
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Principal Investigator |
MOROHASHI Ken-ichirou Kyushu University, Graduate School of Medical Sciences, Professor (30183114)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMA Yuichi National Istitute for Basic Biology, Division for Sex differentiation, Post-doctoral Fellow (80425420)
MOHAMAD Zubair 基礎生物学研究所, 性差生物学研究部門, 特別協力研究員 (70419860)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥16,830,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥2,130,000)
Fiscal Year 2007: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
Fiscal Year 2006: ¥7,600,000 (Direct Cost: ¥7,600,000)
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| Keywords | enhancer / gene expression / tissue specificity / adrenal gland / steroid hormone / adrenal cortex / development |
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| Research Abstract |
The adrenal cortex plays a crucial role for homeostasis of ionic and glucose concentration through synthesis of mineralocorticoid and glucocorticoid, while Ad4BP/SF-1, a member of nuclear receptor superfamily, plays roles for development and steroidogenic gene regulation of the adrenal cortex. In order to elucidate the mechanism for the tissue development, we identified adrenal specific enhancer of Ad4BP/SF-1 gene and examined the function of the nucleotide sequences required for the adrenal specific expression. Subsequently, we investigated the transcription factors which bind to the functional sequences. As the consequence, we found that Hox/Pbx/Meis complex activates enhancer function through binding.
It has been discussed that the fetal adrenal cortex and adult adrenal cortex originate from mutually distinct cells. The adrenal specific enhancer identified by our current study drives gene expression only in the fetal but not adult adrenal cortex. Using the enhancer, we produced mice in which Cre recombinase transgene is induced specifically in the fetal adrenal. The mice were crossed with ROSA mice to label the cells in which the fetal adrenal enhancer turned on once, and examined cell lineage of the cells. As the consequence, we demonstrated that a certain population of the fetal adrenal cortex has the potential to differentiate into the adult adrenal cortex, and this ability for differentiation can be detected at an early stage of the tissue and thereafter disappears soon.
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