Department of Molecular, Cellular, and Developmental Biology, New Haven, CT, USA.
Dev Biol. 2012 Sep 15;369(2):298-307. doi: 10.1016/j.ydbio.2012.07.003. Epub 2012 Jul 14.
Fibroblast growth factor (Fgf) and Wnt signaling are necessary for the intertwined processes of tail elongation, mesodermal development and somitogenesis. Here, we use pharmacological modifiers and time-resolved quantitative analysis of both nascent transcription and protein phosphorylation in the tailbud, to distinguish early effects of signal perturbation from later consequences related to cell fate changes. We demonstrate that Fgf activity elevates Wnt signaling by inhibiting transcription of the Wnt antagonists dkk1 and notum1a. PI3 kinase signaling also increases Wnt signaling via phosphorylation of Gsk3β. Conversely, Wnt can increase signaling within the Mapk branch of the Fgf pathway as Gsk3β phosphorylation elevates phosphorylation levels of Erk. Despite the reciprocal positive regulation between Fgf and Wnt, the two pathways generally have opposing effects on the transcription of co-regulated genes. This opposing regulation of target genes may represent a rudimentary relationship that manifests as out-of-phase oscillation of Fgf and Wnt target genes in the mouse and chick tailbud. In summary, these data suggest that Fgf and Wnt signaling are tightly integrated to maintain proportional levels of activity in the zebrafish tailbud, and this balance is important for axis elongation, cell fate specification and somitogenesis.
成纤维细胞生长因子（Fgf）和 Wnt 信号对于尾巴伸长、中胚层发育和体节形成的交织过程是必要的。在这里，我们使用药理学修饰剂和尾部芽中新生转录和蛋白质磷酸化的时间分辨定量分析，将信号干扰的早期效应与与细胞命运变化相关的后期后果区分开来。我们证明 Fgf 活性通过抑制 Wnt 拮抗剂 dkk1 和 notum1a 的转录来增加 Wnt 信号。PI3 激酶信号还通过磷酸化 Gsk3β 增加 Wnt 信号。相反，Wnt 可以通过增加 Erk 的磷酸化水平来增加 Fgf 途径中 Mapk 分支的信号。尽管 Fgf 和 Wnt 之间存在相互正向调节，但这两个途径通常对共同调节基因的转录具有相反的影响。靶基因的这种反向调节可能代表一种基本关系，表现在小鼠和鸡尾部芽中 Fgf 和 Wnt 靶基因的非同步振荡。总之，这些数据表明 Fgf 和 Wnt 信号紧密结合，以维持斑马鱼尾部芽中活性的比例水平，这种平衡对于轴伸长、细胞命运特化和体节形成很重要。
