Docking protein SNT1 is a critical mediator of fibroblast growth factor signaling during Xenopus embryonic development

Keiko Akagi, Eui Kyun Park, Kathleen Mood, Ira O. Daar

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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.

Original languageEnglish
Pages (from-to)216-228
Number of pages13
JournalDevelopmental Dynamics
Volume223
Issue number2
DOIs
StatePublished - 2002

Keywords

  • Fibroblast growth factor receptor
  • FRS-2
  • Mesoderm
  • SNTI
  • Xenopus

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