1995 Fiscal Year Final Research Report Summary
Investigation of the basic process of cell differentiation utilizing mutant animals of crystallin regulators
| Project/Area Number |
05404084
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Developmental biology
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| Research Institution | Osaka University |
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Principal Investigator |
KONDOH Hisato Osaka University, Institute for Molecular and Cellular Biology, Professor, 細胞生体工学センター, 教授 (70127083)
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| Co-Investigator(Kenkyū-buntansha) |
HIGAASHI Yujiro Osaka University, Institute for Molecular and Cellular Biology, Associate Profes, 細胞生体工学センター, 助教授 (30181069)
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| Project Period (FY) |
1993 – 1995
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| Keywords | Lens differentiation / Transcription factors / Sox / deltaEF1 |
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| Research Abstract |
We have aimed at elucidation of the process of lens differentiation as a paradigm of cell differentiation with special attention to transcriptional regulation. It is remarkable that lens cell undergo terminal differentiation exceptionally early in embryogenesis. Onset of lens differentiation is marked by initiation of crystallin gene expression in addition to morphological change of the tissue. We focused on regulation of delta-crystallin gene of the chicken because delta-crystallin is the earliest and the most abundantly synthesized crystallin in avian lenses.
Mutational analysis of the delta-crystallin enhancer core identifed two positive regulatory elements which are interdependent. From this and EMSA of lens nuclear extract, it was concluded these two elements correspond to binding sites of two distinct activators, deltaEF2 (Sox-1 to 3) and deltaEF3. A repressor deltaEF1 modulates the activity of deltaEF3. It was also shown that Sox binding is required for the promoter activity of the mouse gamma-crystallin gene, providing evidence that diversified crystallin genes are regulated, at least partly, by a common mechanism.
The Sox proteins 1 to 3 are shown to be essential for crystallin regulation, and from chronology and spatial distribution of their expression they are good candidates as a key factor of lens differentiation. Pax-6 also seems involved in these processes, but its contribution seems to be in larger number of steps than only provoking lens diffentiation. It looks as if Pax-6 is involved in endowment of eyeness to the tissues in global terms, while Sox-1 to 3 are in determination of lensness in the ectoderm. These two factors appear essential for eliciting lens differentiation, but by themselves they are not sufficient, and more intrinsic and extrinsic factors are probably necessary for lens differentiation to occur. deltaEF3, currently under investigation, may be one of these essential factors.
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Research Products
(13 results)
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[Publications] Sekido, R., Murai, K., Funahashi, J., Kamachi, Y., Fujisawa-sehara, A., Nabeshima, Y.and Kondoh, H.: "d-Crystallin enhancer binding protein dEF1 is a repressor of E2-box-mediated gene activation." Mol.Cell.Biol.14. 5692-5700 (1994)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kamachi, Y., Sockanathan, S., Liu, Q., Breitman, M., Lovell-Badge, R.and Kondoh, H.: "Invovement of SOX proteins in lens-specific activation of crystallin genes." EMBOJ.14. 3510-3519 (1995)
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「研究成果報告書概要(欧文)」より
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[Publications] Sekido, R., Takagi, T., Okanami, M., Moribe, H., Yamamura, M., Higashi, Y.and Kondoh, H.: "Organization of the gene for transcriptional repressor dEF1 and cross-species conservation of encoded protein domains." Gene. (in press). (1996)
Description
「研究成果報告書概要(欧文)」より
