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Published on: May 26, 2011
Docking protein SNT1 is a critical mediator of fibroblast growth factor signaling during Xenopus embryonic
Keiko Akagi1, Eui Kyun Park, Kathleen Mood
1Regulation of Cell Growth Laboratory, National Cancer Institute-Frederick, Frederick, MD 21702, USA.
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.
Insights
The docking protein SNT1/FRS2 (fibroblast growth factor receptor substrate 2) is crucial for Xenopus development. It mediates fibroblast growth factor (FGF) signaling, essential for mesoderm formation and embryonic structure development.
Area of Science:
- Developmental Biology
- Cell Signaling
- Molecular Biology
Background:
- Fibroblast growth factor receptor substrate 2 (SNT1/FRS2) is known to transmit signals from growth factor receptors to the MAP kinase cascade.
- However, its specific biological roles during embryonic development remain largely uncharacterized.
Purpose of the Study:
- To investigate the function of the Xenopus homolog of SNT1/FRS2 (XSNT1) in early embryonic development.
- To elucidate the role of XSNT1 in mediating fibroblast growth factor (FGF) signaling pathways.
Main Methods:
- Expression pattern analysis of XSNT1 during Xenopus development.
- Gain-of-function experiments using ectopic XSNT1 expression.
- Loss-of-function studies utilizing antisense XSNT1 morpholino oligonucleotides (XSNT-AS).
- Assessment of MAP kinase activity and mesodermal marker expression.
Main Results:
- XSNT1 expression parallels that of fibroblast growth factor receptor-1 (FGFR1) in Xenopus embryos.
- Ectopic XSNT1 enhanced FGF receptor-induced defects and boosted MAP kinase activity and mesodermal marker expression.
- Loss-of-function studies with XSNT-AS resulted in severe malformations, disrupted muscle and notochord formation, and inhibited FGFR-induced MAP kinase activation.
- XSNT-AS blocked FGFR-mediated mesoderm induction and elongation movements in ectodermal explants.
Conclusions:
- XSNT1 is a critical mediator of FGF signaling in Xenopus.
- XSNT1 plays an essential role in mesoderm formation and overall early embryonic development.
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