Docking protein SNT1 is a critical mediator of fibroblast growth factor signaling during Xenopus embryonic development.
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.
Akagi
Keiko
K
Regulation of Cell Growth Laboratory, National Cancer Institute-Frederick, Frederick, MD 21702, USA.
Kyun Park
Eui
E
Mood
Kathleen
K
Daar
Ira O
IO
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D004625:Embryo, Nonmammalian / Q000378:metabolism; D047108:Embryonic Development; D016220:Fibroblast Growth Factor 1 / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D020935:MAP Kinase Signaling System; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008648:Mesoderm / Q000378:metabolism; D008969:Molecular Sequence Data; D009024:Morphogenesis; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014714:Vertebrates / Q000235:genetics; D029867:Xenopus Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C106534:FRS2 protein, human; D008565:Membrane Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D010750:Phosphoproteins; D017468:Receptors, Fibroblast Growth Factor; D029867:Xenopus Proteins; D016220:Fibroblast Growth Factor 1; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1