Journal
MECHANISMS OF DEVELOPMENT
Volume 109, Issue 2, Pages 195-204Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0925-4773(01)00524-X
Keywords
mesoderm; Xenopus; SNT-1; FRS2 alpha; Laloo; fibroblast growth factor
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Funding
- NIGMS NIH HHS [R01-GM61671, R01-GM59432, R01 GM061671, R01 GM059432-02] Funding Source: Medline
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Members of the fibroblast growth factor (FGF) ligand family play a critical role in mesoderm formation in the frog Xenopus laevis. While many components or the signaling cascade triggered by FGF receptor activation have been identified, links between these intracellular factors and the receptor itself have been difficult to establish. We report here the characterization of Xenopus SNT-1 (FRS2 alpha), a scaffolding protein previously identified as a mediator of FGF activity in other biological contexts. SNT-1 is widely expressed during early Xenopus development. consistent with a role for this protein in mesoderm formation. Ectopic SNT-1 induces mesoderm in Xenopus ectodermal explants, synergizes with low levels of FGF, and is blocked by inhibition of Ras activity, suggesting that SNT-1 functions to transmit signals from the FGF receptor during mesoderm formation. Furthermore, dominant-inhibitory SNT-1 mutants inhibit mesoderm induction by FGF. suggesting that SNT-1 is required for this process. Expression of dominant-negative SNT-1 in intact embryos blocks mesoderm formation and dramatically disrupts trunk and tail development, indicating a requirement for SNT-1. or a related factor inhibited by the mutant construct, during axis formation in vivo. Finally, we demonstrate that SNT-1 physically associates with the Src-like kinase Laloo, and that SNT-1 activity is required for mesoderm induction by Laloo, suggesting that SNT-1 and Latoo function as components of a signaling complex during mesoderm formation in the vertebrate. (C) 2001 Elsevier Science Ltd. All rights reserved.
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