| Project/Area Number |
09680733
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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 | OKAZAKI NATIONAL RESEARCH INSTITUTES |
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Principal Investigator |
MOCHII Makoto OKAZAKI NATL, RES.INST., NATL.INST.BASIC BIOL., RESEARCH ASSOCIATE, 基礎生物学研究所, 助手 (90202358)
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| Co-Investigator(Kenkyū-buntansha) |
KOSAKA Mitsuko JAPAN SCIENECE AND TECHNOLOGY CORPORATION, PRESTO, RESEARCHER, さきがけ21, 専任研究員
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1997: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | PIGMENTED EPITHELIAL CELLS / TRANSDIFFERENTIATION / MITF / CHICKEN / QUAIL / pax6 / FGF / EGF |
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| Research Abstract |
Vertebrate pigmented epithelial cells (PECs) are unique in their ability to transdifferentiate to lens and neural retinal cells.To elucidate the molecular mechanisms underlying the multi-potency of PECs, we focused on the role and regulation of Mitf, a basic-helix-loop-helix-zipper transcriptional factor.
Chicken Mitf is first detected in the proximal region of the optic vesicle, a presumptive pigmented epithelium, at a stage when no other markers for PECs are detected.The expression increases according to the PEC differentiation both in vivo and in vitro.Mitf expression is down-regulated by FGF and EGF treatments, which induce dedifferentiation and transdifferentiation.Overexpression of Mitf using a retrovirus vector supports expression of pigment cell specific genes, mmpll5 and tyrosinase, and inhibits transdifferentiation
We found that a silver mutation in Japanese quail is caused by a loss-of-function mutation in the Mitf.A part of PECs in the silver quail spontaneously transdifferentiate to neural retinal cells in vivo.Isolated PECs from the silver mutant frequently transdifferentiate to both lens and neural cells in vitro with no addition of growth factors, while either FGF or EGF is required for wild type PECs to transdifferentiate.
These results demonstrate that Mitf has a critical role in regulation of transdifferentiation and suggest that the regulational mechanism for Mitf expression should be analysed to reveal the molecular mechanisms underlying the multi-potency OF pigmented epithelial cells.
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