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Abstract
Although FGF signaling plays an integral role in the migration and patterning of mesoderm
at gastrulation, the mechanism and downstream targets of FGF activity have remained
elusive. Here, we demonstrate that FGFR1 orchestrates the epithelial to mesenchymal
transition and morphogenesis of mesoderm at the primitive streak by controlling Snail
and E-cadherin expression. Furthermore, we show that FGFR1 functions in mesoderm cell
fate specification by positively regulating Brachyury and Tbx6 expression. Finally,
we provide evidence that the attenuation of Wnt3a signaling observed in Fgfr1 -/-
embryos can be rescued by lowering E-cadherin levels. We propose that modulation of
cytoplasmic beta-catenin levels, associated with FGF-induced downregulation of E-cadherin,
provides a molecular link between FGF and Wnt signaling pathways at the streak.