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Identification of Sef, a novel modulator of FGF signalling

Nature Cell Biology volume 4, pages 165–169 (2002)Cite this article

Abstract

Fibroblast growth factors (FGFs) are members of a family of some 30 secreted proteins important in the regulation of cellular proliferation, migration, differentiation and survival1,2,3,4. Here we report the identification of a novel modulator of FGF signal transduction, sef, isolated from a zebrafish embryo library through an in situ hybridization screen. The sef gene encodes a transmembrane protein, and belongs to the synexpression group that includes some of the fgf genes. Sef expression is positively regulated by FGF, and ectopic expression of sef in zebrafish or Xenopus laevis embryos specifically inhibits FGF signalling. In co-immunoprecipitation assays, the intracellular domain of Sef interacts with FGF receptors, FGFR1 and FGFR2. Injection of antisense sef morpholino oligos mimicked the phenotypes observed by ectopic fgf8 expression, suggesting that Sef is required to limit FGF signalling during development.

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Figure 1: FGF signalling regulates sef expression.
Figure 2: Ectopic expression of Sef suppresses FGF signalling.
Figure 3: Sef functions to attenuate FGF activity during early development.
Figure 4: Co-immunopreciptation of Sef and Xenopus FGF receptors.

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Accessions

GenBank/EMBL/DDBJ

Data deposits

  • The sef sequence is deposited at Genbank under the accession number AF364103.

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Acknowledgements

We are grateful to E. Weinberg, D. Stainier, and M. Halpern for zebrafish lines; M. Whitman, J. Breen, M. Ekker, E. M. De Robertis and A. B. Roberts for constructs; and E. Laver for zebrafish technical assistance. N. Hukriede, A. Kawahara, L. Kodjabachian and I. Daar for discussions and critical reading of the manuscript. We thank B. Thisse and C. Thisse for sharing unpublished results. R.F. was supported by grants DE13248, HL65301 and RR15555 from the NIH.

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Authors and Affiliations

  1. Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, 20892, MD, USA

    Michael Tsang, Tetsuhiro Kudoh & Igor B Dawid

  2. Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, 04074, ME, USA

    Robert Friesel

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  1. Michael Tsang
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  2. Robert Friesel
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  3. Tetsuhiro Kudoh
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  4. Igor B Dawid
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Corresponding author

Correspondence to Igor B Dawid.

Supplementary information

Supplementary Figures

Figure S1 Sef sequence analysis. (PDF 432 kb)

Figure S2 Ectopic expression of sef in Zebrafish and Xenopus embryos.

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Tsang, M., Friesel, R., Kudoh, T. et al. Identification of Sef, a novel modulator of FGF signalling. Nat Cell Biol 4, 165–169 (2002). https://doi.org/10.1038/ncb749

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