Because fibroblast growth factor (FGF) signalling is important in many developmental processes, its intensity and duration during embryogenesis must be closely regulated. Tsang et al. reveal on that mitogen-activated protein kinase phosphatase 3 (MKP3) regulates the FGF/RAS/MAPK signalling pathway through negative feedback in early zebrafish embryos, and that this pathway helps to establish axial polarity. MKP3, whose expression is controlled by FGF signalling through the RAS/MAPK pathway,inhibits MAPK activity. The researchers show that the experimental alteration of mkp3 expression disrupts dorsoventral patterning at gastrulation. Endogenous mkp3 expression, they report, is initiated by a maternalβ-catenin signal but its expression quickly comes under the control of FGF signalling. These results indicate that the tight regulation of FGF signalling, which the authors show here is necessary for specifying axial polarity, is achieved by having MKP3 expression in place before FGF signalling starts.
