MOLECULAR MECHANISMS UNDERLYING THE MULTIPOTENCY OF DIFFERENTIATED PIGMENTED EPITHELIAL CELLS.

脊椎动物色素上皮细胞（佩奇）具有向透镜和神经视网膜细胞转分化的独特能力，为了阐明佩奇多能性的分子机制，我们重点研究了Mitf（一种碱性螺旋环螺旋拉链转录因子）的作用和调控。在没有检测到佩奇的其他标志物的阶段。在体内和体外，表达根据PEC分化而增加。Mitf表达被FGF和EGF处理下调，其诱导去分化和转分化。使用逆转录病毒载体过表达Mitf支持色素细胞特异性基因mmpll5和酪氨酸酶的表达，并且抑制转分化我们发现日本鹌鹑的银突变是由Mitf中的功能缺失突变引起的。银鹌鹑中的部分佩奇在体内自发地转分化为神经视网膜细胞。来自银突变体的分离的佩奇在不添加生长因子的情况下在体外频繁地转分化为透镜和神经细胞，这些结果表明Mitf在色素上皮细胞转分化的调控中具有重要作用，并提示应分析Mitf表达的调控机制，以揭示色素上皮细胞多能性的分子机制。

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 transdifferentiationWe 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.