Crosstalk between Fgf and Wnt signaling in the zebrafish tailbud.

Crosstalk between Fgf and Wnt signaling in the zebrafish tailbud.
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DOI:
10.1016/j.ydbio.2012.07.003
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发表时间:
2012-09-15
影响因子:
2.7
通讯作者:
Holley SA
Holley SA
中科院分区:
生物学3区
文献类型:
--
作者:
Stulberg MJ;Lin A;Zhao H;Holley SA

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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 Gskβ 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.
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