Zebrafish Ext2 is necessary for Fgf and Wnt signaling, but not for Hh signaling

BMC Developmental Biology

Johan Ledin³  Beata Filipek-Gorniok¹  Sabine Fischer² 

[1] Department of Medical Biochemistry and Microbiology, Uppsala University, Husarg. 3,751 23 Uppsala, Sweden;European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany;Department of Organismal Biology, Science for Life Laboratory, Uppsala University, Norbyv. 18A, 752 36 Uppsala, Sweden

关键词: Hh;    Wnt;    Fgf;    Heparan;    HSPG;    Ext2;    Zebrafish;   

Others  :  1087444
DOI  :  10.1186/1471-213X-11-53

 received in 2011-02-14, accepted in 2011-09-05,  发布年份 2011

【 摘 要 】

Background

Heparan sulfate (HS) biosynthesis is tightly regulated during vertebrate embryo development. However, potential roles for HS biosynthesis in regulating the function of paracrine signaling molecules that bind to HS are incompletely understood.

Results

In this report we have studied Fgf, Wnt and Hedgehog (Hh) signaling in ext2 mutants, where heparan sulfate content is low. We found that Fgf targeted gene expression is reduced in ext2 mutants and that the remaining expression is readily inhibited by SU5402, an FGF receptor inhibitor. In the ext2 mutants, Fgf signaling is shown to be affected during nervous system development and reduction of Fgf ligands in the mutants affects tail development. Also, Wnt signaling is affected in the ext2 mutants, as shown by a stronger phenotype in ext2 mutants injected with morpholinos that partially block translation of Wnt11 or Wnt5b, compared to injected wild type embryos. In contrast, Hh dependent signaling is apparently unaffected in the ext2 mutants; Hh targeted gene expression is not reduced, the Hh inhibitor cyclopamine is not more affective in the mutants and Hh dependent cell differentiation in the retina and in the myotome are normal in ext2 mutants. In addition, no genetic interaction between ext2 and shha during development could be detected.

Conclusion

We conclude that ext2 is involved in Fgf and Wnt signaling but not in Hh signaling, revealing an unexpected specificity for ext2 in signaling pathways during embryonic development. Thus, our results support the hypothesis that regulation of heparan sulfate biosynthesis has distinct instructive functions for different signaling factors.

【 授权许可】

   
2011 Fischer et al; licensee BioMed Central Ltd.

【 图 表 】

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