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Zebrafish Ext2 is necessary for Fgf and Wnt signaling, but not for Hh signaling
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
2011 (English)In: BMC Developmental Biology, ISSN 1471-213X, Vol. 11, 53- p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2011. Vol. 11, 53- p.
Keyword [en]
Zebrafish, Ext2, HSPG, Heparan, Fgf, Wnt, Hh
National Category
Biological Sciences
URN: urn:nbn:se:uu:diva-160420DOI: 10.1186/1471-213X-11-53ISI: 000295412800001OAI: diva2:450885
Available from: 2011-10-24 Created: 2011-10-24 Last updated: 2011-10-24Bibliographically approved

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Department of Medical Biochemistry and MicrobiologyEvolution and Developmental BiologyScience for Life Laboratory, SciLifeLab
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