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Vol. 15, No. 9, pp. 1152-1166, May 1, 2001
1 Wellcome/CRC Institute, Cambridge CB2 1QR, UK and
Department of Zoology, University of Cambridge CB2 3EJ, UK;
2 Department of Anatomy, University of Cambridge,
Cambridge CB2 3DY, UK
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.
[Key Words: Sprouty; FGF signaling; gastrulation; convergent extension]
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