1998 Fiscal Year Final Research Report Summary
Analysis of the Notch-HES pathway that regulates mammalian neurogenesis
| Project/Area Number |
09670009
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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 |
General anatomy (including Histology/Embryology)
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
ISHIBASHI Makoto Kyoto Univ.Graduate School of Medicine, Dept.of Anat.& Develop.Biol., Lecturer, 医学研究科, 助手 (30232341)
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| Co-Investigator(Kenkyū-buntansha) |
SHIOTA Kohei Kyoto Univ.Graduate School of Medicine, Dept.of Anat.& Develop.Biol., Professor, 医学研究科, 教授 (80109529)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Neural precursor cell / Differentiation / Transcriptional regulation / Myogenesis / HES / Notch / Gene targeting |
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| Research Abstract |
In order to elucidate the transcriptional regulation of mammalian neurogenesis, we analyzed the roles HES-1, which is a mammalian homolog of Drosophila hairy and Enhancer of split genes, in neurogenesis and obtained the following results.
1. HES-l was intensely expressed in immature tissues of rodent embryos, including neural and muscular tissues, and the expression level declined along with tissue differentiation.
2. HES- 1 suppressed the differentiation of cultured myogenic cells which is mediated by Myo-D.
3. When HES-l was induced in neural precursor cells in the central nervous system of mouse embryos, it completely inhibited neuronal differentiation.
4. In mice lacking HES-1, the expression of Mashl increased and premature neurogenesis occurred. These mice had cranial neural tube defects resulting from the failure of neural tube closure.
5. When the retinal tissue of fetal mice lacking HES-l was cultured in vitro, the neural retina showed premature and abnormal differentiation.
6. From an in vitro promotor analysis of mouse HES-1 gene, it was revealed that HES-1 expression is regulated by itself (negative autoregulation).
From these observations, it was concluded that HES-I negatively regulates mammalian neurogenesis.
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