Control of neural crest cell fate by the Wnt signalling pathway
Control of neural crest cell fate by the Wnt signalling pathway
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DOI：
10.1038/24620
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发表时间：
1998-11-26
期刊：
影响因子：
64.8
通讯作者：
Raible, DW
中科院分区：
文献类型：
--
作者：
Dorsky, RI;Moon, RT;Raible, DW
环境信号在神经嵴的发育中是重要的，在此过程中，多能祖细胞必须从几种命运中选择（1-3）。然而，这些环境信号的性质是未知的。先前的斑马鱼颅神经嵴命运图显示，色素细胞的谱系限制克隆来自靠近神经龙骨的内侧细胞，而神经元克隆来自远离神经龙骨的外侧细胞（4），Wnt-1和Wnt-3a是影响神经嵴命运的候选基因，因为它们在内侧嵴细胞附近表达，而不是外侧嵴细胞。在这里，我们确定Wnt信号在调节神经嵴的命运的作用，通过注射信使RNA到单个的，前迁移的神经嵴细胞的斑马鱼，注射细胞的谱系分析表明，激活Wnt信号通过注射编码细胞质β-连环蛋白的mRNA促进色素细胞的形成，在神经元和神经胶质细胞的费用。相反，通过注射编码截短形式的转录因子Tcf-3或显性负性Wnt的mRNA来抑制Wnt途径，以色素细胞为代价促进神经元的命运。我们的结论是，内源性Wnt信号正常促进色素细胞形成的内侧嵴细胞，从而有助于神经嵴细胞命运的多样性。
Environmental signals are important in the development of neural crest, during which process multipotent progenitor must choose from several fates(1-3). However, the nature of these environmental signals is unknown. A previous fate map of zebrafish cranial neural crest showed that lineage-restricted clones of pigment cells arise hom medial cells near the neural keel, and that clones of neurons arise from lateral cells farther from the neural keel(4), Wnt-1 and Wnt-3a are candidate genes for influencing neural crest fate, as they are expressed next to medial, but not lateral, crest cells. Here we determine the role of Wnt signals in modulating the fate of neural crest by injecting messenger RNAs into single, premigratory neural crest cells of zebrafish, Lineage analysis of injected cells shows that activation of Wnt signalling by injection of mRNA encoding cytoplasmic beta-catenin promotes pigment-cell formation at the expense of neurons and glia. Conversely, inhibition of the Wnt pathway, by injection of mRNAs encoding either a truncated form of the transcription factor Tcf-3 or a dominant-negative Wnt, promotes neuronal fates at the expense of pigment cells. We conclude that endogenous Wnt signalling normality promotes pigment-cell formation by medial crest cells and thereby contributes to the diversity of neural crest cell fates.