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

  1. Author:
    Akagi, K.
    Park, E. K.
    Mood, K.
    Daar, I. O.

  2. Author Address

    NCI, Regulat Cell Growth Lab, Bldg 560, Room 22-3, Frederick, MD 21702 USA. NCI, Regulat Cell Growth Lab, Frederick, MD 21702 USA. Daar IO NCI, Regulat Cell Growth Lab, Bldg 560, Room 22-3, Frederick, MD 21702 USA.
    1. Year: 2002
  2. Journal: Developmental Dynamics
    1. 223
    2. 2
    3. Pages: 216-228
  4. Type of Article: Article
  1. 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 ALAP 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. (C) 2002 Wiley-Liss, Inc.

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