Xenopus Sprouty2 inhibits FGF-mediated gastrulation movements but does not affect mesoderm induction and patterning.
Signal transduction through the FGF receptor is essential for the specification of the vertebrate body plan. Blocking the FGF pathway in early Xenopus embryos inhibits mesoderm induction and results in truncation of the anterior-posterior axis. The Drosophila gene sprouty encodes an antagonist of FGF signaling, which is transcriptionally induced by the pathway, but whose molecular functions are poorly characterized. We have cloned Xenopus sprouty2 and show that it is expressed in a similar pattern to known FGFs and is dependent on the FGF/Ras/MAPK pathway for its expression. Overexpression of Xsprouty2 in both embryos and explant assays results in the inhibition of the cell movements of convergent extension. Although blocking FGF/Ras/MAPK signaling leads to an inhibition of mesodermal gene expression, these markers are unaffected by Xsprouty2, indicating that mesoderm induction and patterning occurs normally in these embryos. Finally, using Xenopus oocytes we show that Xsprouty2 is an intracellular antagonist of FGF-dependent calcium signaling. These results provide evidence for at least two distinct FGF-dependent signal transduction pathways: a Sprouty-insensitive Ras/MAPK pathway required for the transcription of most mesodermal genes, and a Sprouty-sensitive pathway required for coordination of cellular morphogenesis.
Nutt
S L
SL
Wellcome/CRC Institute, Cambridge CB2 1QR, UK and Department of Zoology, University of Cambridge CB2 3EJ, UK.
Dingwell
K S
KS
Holt
C E
CE
Amaya
E
E
D000595:Amino Acid Sequence; D000818:Animals; D019521:Body Patterning; D002118:Calcium; D004625:Embryo, Nonmammalian; D004627:Embryonic Induction; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D005775:Gastrula; D018507:Gene Expression Regulation, Developmental; D008648:Mesoderm; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics
D009419:Nerve Tissue Proteins; D017468:Receptors, Fibroblast Growth Factor; C404992:Spry2 protein, rat; D005346:Fibroblast Growth Factors; D020928:Mitogen-Activated Protein Kinases; D002118:Calcium