BMP-4 upregulates kit expression in mouse melanoblasts prior to the kit-dependent cycle of melanogenesis
BMP-4 upregulates kit expression in mouse melanoblasts prior to the kit-dependent cycle of melanogenesis
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DOI：
10.1038/sj.jid.5701136
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发表时间：
2008-05-01
影响因子：
6.5
通讯作者：
Soma, Yoshinao
中科院分区：
文献类型：
--
作者：
Kawakami, Tamihiro;Kimura, Satoko;Soma, Yoshinao
编码Kit和Kit配体（KL）的基因在黑素母细胞的分化中起着至关重要的作用。我们先前建立了三种不朽但不同的小鼠神经嵴（NC）细胞群。NCCmelb4M5细胞不表达Kit，独立于KL生长；它们有可能分化成NCCmelb4细胞，这是kit阳性的黑素细胞前体。NCCmelan5细胞具有分化黑色素细胞的特征。三种细胞系均表现出骨形态发生蛋白（BMP）受体的表达。BMP-4上调了大多数未成熟NCCmelb4M5细胞中Kit蛋白和mRNA的表达。Noggin是一种BMP-4拮抗剂，可显著降低BMP-4诱导的Kit表达。Western blot分析显示，外源性BMP-4可导致NCCmelb4M5细胞中Smads的磷酸化。利用转染的Kit启动子报告子，我们发现BMP-4可以激活转染的NCCmelb4M5细胞中的Kit启动子。我们得出结论，BMP-4是活跃的，并参与了Kit在大多数未成熟黑素细胞前体上的表达调节。我们利用野生型小鼠原代NC细胞进一步研究了BMP-4的体外影响。与稀释剂处理的对照相比，在培养基中添加BMP-4增加了kit阳性细胞的数量。我们已经确定BMP-4是产前kit阴性黑素母细胞进入kit依赖周期之前的一个重要因素。
Genes encoding Kit and the Kit ligand (KL) play essential roles in the differentiation of melanoblasts. We previously established three immortal but distinct cell populations of mouse neural crest (NC) cells. NCCmelb4M5 cells do not express Kit and grow independently of KL; they have the potential to differentiate into NCCmelb4 cells, which are Kit-positive melanocyte precursors. NCCmelan5 cells show the characteristics of differentiated melanocytes. All three cell lines demonstrated bone morphogenetic protein (BMP) receptor expression. BMP-4 upregulated Kit protein and mRNA expression in most immature NCCmelb4M5 cells. Noggin, a BMP-4 antagonist, dramatically decreased the Kit expression induced by BMP-4. Western blot analysis revealed that extrinsic BMP-4 leads to the phosphorylation of Smads in NCCmelb4M5 cells. Using transfected Kit-promoter reporter, we showed BMP-4 could activate Kit promoter in transfected NCCmelb4M5 cells. We conclude that BMP-4 is active and is involved in the regulation of Kit expression on most immature melanocyte precursors. We further investigated the influence of BMP-4 in vitro using primary NC cells cultured from wild-type mice. Addition of BMP-4 to the medium increased the number of Kit-positive cells compared to diluent-treated controls. We have identified BMP-4 as an important factor for prenatal Kit-negative melanoblasts just prior to entering the Kit-dependent cycle of melanogenesis.