Docking Protein SNT1 Is a Critical Mediator of Fibroblast Growth Factor Signaling During Xenopus Embryonic Development

Dev Dyn. 2002 Mar;223(2):216-28. doi: 10.1002/dvdy.10048.

Abstract

The docking protein SNT1/FRS2 (fibroblast growth factor receptor substrate 2) is implicated in the transmission of extracellular signals from several growth factor receptors to the mitogen-activated protein (MAP) kinase signaling cascade, but its biological function during development is not well characterized. Here, we show that the Xenopus homolog of mammalian SNT1/FRS-2 (XSNT1) plays a critical role in the appropriate formation of mesoderm-derived tissue during embryogenesis. XSNT1 has an expression pattern that is quite similar to the fibroblast growth factor receptor-1 (FGFR1) during Xenopus development. Ectopic expression of XSNT1 markedly enhanced the embryonic defects induced by an activated FGF receptor, and increased the MAP kinase activity as well as the expression of a mesodermal marker in response to FGF receptor signaling. A loss-of-function study using antisense XSNT1 morpholino oligonucleotides (XSNT-AS) shows severe malformation of trunk and posterior structures. Moreover, XSNT-AS disrupts muscle and notochord formation, and inhibits FGFR-induced MAP kinase activation. In ectodermal explants, XSNT-AS blocks FGFR-mediated induction of mesoderm and the accompanying elongation movements. Our results indicate that XSNT1 is a critical mediator of FGF signaling and is required for early Xenopus development.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Animals
  • Embryo, Nonmammalian / metabolism
  • Embryonic Development
  • Fibroblast Growth Factor 1 / physiology*
  • Gene Expression Regulation, Developmental
  • In Situ Hybridization
  • MAP Kinase Signaling System*
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Mesoderm / metabolism
  • Molecular Sequence Data
  • Morphogenesis
  • Oligodeoxyribonucleotides, Antisense / pharmacology
  • Phosphoproteins / biosynthesis
  • Phosphoproteins / genetics
  • Phosphoproteins / physiology*
  • Receptor Protein-Tyrosine Kinases / biosynthesis
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / physiology*
  • Receptor, Fibroblast Growth Factor, Type 1
  • Receptors, Fibroblast Growth Factor / biosynthesis
  • Receptors, Fibroblast Growth Factor / genetics
  • Receptors, Fibroblast Growth Factor / physiology*
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Species Specificity
  • Vertebrates / genetics
  • Xenopus Proteins / biosynthesis
  • Xenopus Proteins / genetics
  • Xenopus Proteins / physiology*
  • Xenopus laevis / embryology*
  • Xenopus laevis / genetics
  • Xenopus laevis / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • FRS2 protein, human
  • Membrane Proteins
  • Oligodeoxyribonucleotides, Antisense
  • Phosphoproteins
  • Receptors, Fibroblast Growth Factor
  • Xenopus Proteins
  • Fibroblast Growth Factor 1
  • Receptor Protein-Tyrosine Kinases
  • Receptor, Fibroblast Growth Factor, Type 1