Planque Nathalie, Raposo Graça, Leconte Laurence, Anezo Oceane, Martin Patrick, Saule Simon
UMR 146, Institut Curie Section de Recherche, Bātiment 110, Centre Universitaire, 91405 Orsay Cedex, France.
J Biol Chem. 2004 Oct 1;279(40):41911-7. doi: 10.1074/jbc.M404964200. Epub 2004 Jul 23.
Mitf encodes a basic helix-loop-helix transcription factor that plays an essential role in the differentiation of the retinal pigmented epithelium (RPE) and neural crest-derived melanocytes. As cells containing melanogenic enzymes (TRP2) are found in Mitf mouse mutants, it is not clear whether Mitf is a downstream factor or a master regulator of melanocyte differentiation. To further study the role of Mitf in committing cells to the melanocyte lineage, we express Mitf in the cultured quail neuroretina cells. This leads to the induction of two types of pigmented cells: neural crest-derived melanocytes, according to their dendritic morphology, physiology, and gene expression pattern are observed together with pigmented epithelial RPE-like cells. The expression of Mitf is lower in pigmented epithelial RPE-like cells than in neural crest-derived melanocytes. Accordingly, overexpression of Mitf in cultured quail RPE causes cells to develop into neural crest-like pigmented cells. Thus, Mitf is sufficient for the proper differentiation of crest-like pigmented cells from retinal cells and its expression level may determine the type of pigment cell induced.
Mitf编码一种碱性螺旋-环-螺旋转录因子,它在视网膜色素上皮(RPE)和神经嵴衍生的黑素细胞的分化中起重要作用。由于在Mitf小鼠突变体中发现了含有黑素生成酶(TRP2)的细胞,因此尚不清楚Mitf是黑素细胞分化的下游因子还是主要调节因子。为了进一步研究Mitf在使细胞定向于黑素细胞谱系中的作用,我们在培养的鹌鹑神经视网膜细胞中表达Mitf。这导致了两种类型色素细胞的诱导:神经嵴衍生的黑素细胞,根据其树突形态、生理学和基因表达模式,与色素上皮RPE样细胞一起被观察到。Mitf在色素上皮RPE样细胞中的表达低于神经嵴衍生的黑素细胞。因此,在培养的鹌鹑RPE中过表达Mitf会使细胞发育成神经嵴样色素细胞。因此,Mitf足以使视网膜细胞正确分化为嵴样色素细胞,其表达水平可能决定所诱导的色素细胞类型。