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Updated: Aug 10, 2026

Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development
Published on: June 15, 2017
Promotion and attenuation of FGF signaling through the Ras-MAPK pathway
1Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Abstract:
The fibroblast growth factors (FGFs) represent a large family of ligands that activate signal transduction pathways leading to diverse biological responses, including many involved in various processes during development. Here, we discuss the discovery of a subset of conserved FGF target genes that encode feedback regulators of FGF signaling itself. Members of the Sprouty, Sef, and mitogen-activated protein kinase phosphatase families are negative modulators of FGF signaling, whereas positive factors that promote FGF signaling include the ETS transcription factors ERM and PEA3 and the transmembrane protein XFLRT3. These molecules affect the FGF signaling cascade at different levels to regulate the final output of the pathway. This multilayered regulation suggests that precise adjustment of FGF signaling is critical in development.
Insights
Fibroblast growth factors (FGFs) regulate development by activating signaling pathways. Conserved FGF target genes provide feedback, with Sprouty, Sef, and phosphatases inhibiting FGF signaling, while ERM, PEA3, and XFLRT3 promote it.
Area of Science:
- Developmental Biology
- Molecular Biology
- Cell Signaling
Background:
- Fibroblast growth factors (FGFs) are crucial ligands initiating signal transduction pathways.
- FGF signaling orchestrates diverse biological responses essential for development.
Purpose of the Study:
- To identify conserved FGF target genes that act as feedback regulators of FGF signaling.
- To elucidate the mechanisms of multilayered regulation within the FGF signaling cascade.
Main Methods:
- Analysis of conserved FGF target genes.
- Identification of genes encoding feedback regulators (positive and negative).
- Characterization of Sprouty, Sef, mitogen-activated protein kinase phosphatase families, ERM, PEA3, and XFLRT3 roles.
Main Results:
- Discovery of conserved FGF target genes encoding feedback regulators.
- Sprouty, Sef, and phosphatases identified as negative modulators of FGF signaling.
- ETS transcription factors ERM and PEA3, and XFLRT3 identified as positive regulators.
Conclusions:
- FGF signaling is subject to multilayered regulation by feedback modulators.
- Precise adjustment of FGF signaling through these regulators is critical for developmental processes.
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