Crosstalk between Fgf and Wnt signaling in the zebrafish tailbud.
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.
Department of Molecular, Cellular, and Developmental Biology, New Haven, CT, USA.
Michael J
MJ
Stulberg
Aiping
A
Lin
Hongyu
H
Zhao
Scott A
SA
Holley
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D020935:MAP Kinase Signaling System; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D013623:Tail / Q000196:embryology / Q000378:metabolism; D060449:Wnt Signaling Pathway; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D017931:DNA Primers; D029961:Zebrafish Proteins; D005346:Fibroblast Growth Factors; D019869:Phosphatidylinositol 3-Kinases; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3