Sl. Nutt et al., Xenopus Sprouty2 inhibits FGF-mediated gastrulation movements but does notaffect mesoderm induction and patterning, GENE DEV, 15(9), 2001, pp. 1152-1166
Signal transduction through the FGF receptor is essential for the specifica
tion of the vertebrate body plan. Blocking the EGF pathway in early Xenopus
embryos inhibits mesoderm induction and results in truncation of the anter
ior-posterior axis. The Drosophila gene sprouty encodes an antagonist of FG
F signaling, which is transcriptionally induced by the pathway, but whose m
olecular functions are poorly characterized. We have cloned Xenopus sprouty
2 and show that it is expressed in a similar pattern to known FGFs and is d
ependent on the FGF/Ras/MAPK pathway for its expression. Overexpression of
Xsprouty2 in both embryos and explant assays results in the inhibition of t
he cell movements of convergent extension. Although blocking FGF/Ras/MAPK s
ignaling leads to an inhibition of mesodermal gene expression, these marker
s are unaffected by Xsprouty2, indicating that mesoderm induction and patte
rning occurs normally in these embryos. Finally, using Xenopus oocytes we s
how that Xsprouty2 is an intracellular antagonist of EGF dependent calcium
signaling. These results provide evidence for at least two distinct FGF-dep
endent signal transduction pathways: a Sprouty-insensitive Ras/MAPK pathway
required for the transcription of most mesodermal genes, and a Sprouty-sen
sitive pathway required for coordination of cellular morphogenesis.