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Sef is a feedback-induced antagonist of Ras/MAPK-mediated FGF signalling

Nature Cell Biology volume 4, pages 170–174 (2002)Cite this article

Abstract

Fibroblast growth factors (FGFs) are pleiotrophic growth factors that control cell proliferation, migration, differentiation and embryonic patterning1. During early zebrafish embryonic development, FGFs regulate dorsoventral patterning by controlling ventral bone morphogenetic protein (BMP) expression2,3. FGFs function by binding and activating high-affinity tyrosine kinase receptors4. FGF activity is negatively regulated by members of the Sprouty family, which antagonize Ras signalling induced by receptor tyrosine kinases3,5,6,7,8. On the basis of similarities in their expression patterns during embryonic development, we have identified five genes that define a synexpression group — fgf8, fgf3, sprouty2, sprouty4, as well as a novel gene, sef (similar expression to fgf genes). Sef encodes a conserved putative transmembrane protein that shares sequence similarities with the intracellular domain of the interleukin 17 receptor9. Here we show that in zebrafish, Sef functions as a feedback-induced antagonist of Ras/Raf/MEK/MAPK-mediated FGF signalling.

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Figure 1: Structure of Sef and comparison of its expression pattern during embryogenesis with other members of the fgf8 synexpression group.
Figure 2: FGF signalling regulates sef expression.
Figure 3: Phenotypes of sef gain- and loss-of-function animals.
Figure 4: Sef rescues defects caused by Fgf8/Ras/Raf/MEK signalling.
Figure 5: Sef rescues cell-cleavage defects that result from Ras/MEK hyperactivity and prevents MAPK activation.

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GenBank/EMBL/DDBJ

Data deposits

  • Sequences of mouse and zebrafish sef cDNAs have been deposited in Genbank with accession numbers AF424804 and AF401232, respectively.

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Acknowledgements

We are grateful to I. Daar, G. R. Martin, J-F. Riou, J. Smith, M. Umbhauer and M. Whitman for providing constructs used in this study. We thank I. Dawid for fruitful discussion and sharing data prior to publication. We thank V. Heyer, M. Koch, C. Lan for technical assistance and O. Nkundwa for caring for the zebrafish. M.F. was funded by the Ministère de l'Enseignement Supérieur de la Recherche, the Ligue Nationale Contre le Cancer and the Centre National de la Recherche Scientifique. B.T., C.T. and S-L.A. were supported by funds from the Institut National de la Santé et de la Recherche Médicale, the Centre National de la Recherche Scientifique, the Hôpital Universitaire de Strasbourg, the Association pour la Recherche sur le Cancer the Ligue Nationale Contre le Cancer and the National Institute of Health (RO1 RR15402). W.L. was funded by a fellowship from INSERM.

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  1. Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, BP 163, Illkirch cedex, 67404, CU de Strasbourg, France

    Maximilian Fürthauer, Wei Lin, Siew-Lan Ang, Bernard Thisse & Christine Thisse

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Correspondence to Christine Thisse.

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Fürthauer, M., Lin, W., Ang, SL. et al. Sef is a feedback-induced antagonist of Ras/MAPK-mediated FGF signalling. Nat Cell Biol 4, 170–174 (2002). https://doi.org/10.1038/ncb750

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