Dorsky R I, Raible D W, Moon R T
Howard Hughes Medical Institute and Department of Pharmacology, University of Washington School of Medicine, Seattle, Washington 98195, USA.
Genes Dev. 2000 Jan 15;14(2):158-62.
We have shown that Wnt signals are necessary and sufficient for neural crest cells to adopt pigment cell fates. nacre, a zebrafish homolog of MITF, is required for pigment cell differentiation. We isolated a promoter region of nacre that contains Tcf/Lef binding sites, which can mediate Wnt responsiveness. This promoter binds to zebrafish Lef1 protein in vitro, and a nacre reporter construct is strongly repressed by dominant-negative Tcf in melanoma cells. Mutation of Tcf/Lef sites abolishes Lef1 binding and reporter function in vivo. Wnt signaling therefore directly activates nacre, which in turn leads to pigment cell differentiation.
我们已经证明，Wnt信号对于神经嵴细胞分化为色素细胞是必需且充分的。小眼畸形相关转录因子（MITF）的斑马鱼同源基因nacre是色素细胞分化所必需的。我们分离出了nacre的一个启动子区域，该区域含有Tcf/Lef结合位点，可介导Wnt反应性。该启动子在体外可与斑马鱼Lef1蛋白结合，并且在黑色素瘤细胞中，nacre报告基因构建体受到显性负性Tcf的强烈抑制。Tcf/Lef位点的突变在体内消除了Lef1结合和报告基因功能。因此，Wnt信号直接激活nacre，进而导致色素细胞分化。
