Dorsky R I, Moon R T, Raible D W
Howard Hughes Medical Institute, Department of Pharmacology, University of Washington School of Medicine, Seattle 98195, USA.
Nature. 1998 Nov 26;396(6709):370-3. doi: 10.1038/24620.
Environmental signals are important in the development of neural crest, during which process multipotent progenitor must choose from several fates. 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 from medial cells near the neural keel, and that clones of neurons arise from lateral cells farther from the neural keel. 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 normally promotes pigment-cell formation by medial crest cells and thereby contributes to the diversity of neural crest cell fates.
环境信号在神经嵴的发育过程中起着重要作用，在此过程中多能祖细胞必须从几种命运中做出选择。然而，这些环境信号的本质尚不清楚。先前斑马鱼颅神经嵴的命运图谱显示，色素细胞的谱系受限克隆源自神经嵴内侧靠近神经嵴的细胞，而神经元克隆则源自远离神经嵴的外侧细胞。Wnt-1和Wnt-3a是影响神经嵴命运的候选基因，因为它们在内侧而非外侧嵴细胞旁边表达。在这里，我们通过将信使RNA注射到斑马鱼单个迁移前神经嵴细胞中来确定Wnt信号在调节神经嵴命运中的作用。对注射细胞的谱系分析表明，通过注射编码细胞质β-连环蛋白的mRNA激活Wnt信号传导会以神经元和神经胶质细胞为代价促进色素细胞的形成。相反，通过注射编码转录因子Tcf-3的截短形式或显性负性Wnt的mRNA来抑制Wnt途径，会以色素细胞为代价促进神经元命运。我们得出结论，内源性Wnt信号通常促进内侧嵴细胞形成色素细胞，从而促进神经嵴细胞命运的多样性。
