Sulf1 has ligand-dependent effects on canonical and non-canonical Wnt signalling

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Wnt signalling plays essential roles during embryonic development and is known to be mis-regulated in human disease. There are many molecular mechanisms that ensure tight regulation of Wnt activity. One such regulator is the heparan-sulfate-specific 6-O-endosulfatase Sulf1. Sulf1 acts extracellularly to modify the structure of heparan sulfate chains to affect the bio-availability of Wnt ligands. Sulf1 could, therefore, influence the formation of Wnt signalling complexes to modulate the activation of both canonical and non-canonical pathways. In this study, we use well-established assays in Xenopus to investigate the ability of Sulf1 to modify canonical and non-canonical Wnt signalling. In addition, we model the ability of Sulf1 to influence morphogen gradients using fluorescently tagged Wnt ligands in ectodermal explants. We show that Sulf1 overexpression has ligand-specific effects on Wnt signalling: it affects membrane accumulation and extracellular levels of tagged Wnt8a and Wnt11b ligands differently, and inhibits the activity of canonical Wnt8a but enhances the activity of non-canonical Wnt11b.

Original languageEnglish
Pages (from-to)1408-1421
Number of pages14
JournalJournal of Cell Science
Issue number7
Early online date13 Feb 2015
Publication statusPublished - 1 Apr 2015

Bibliographical note

© 2015. Published by The Company of Biologists Ltd . This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.


  • Morphogen
  • Development
  • Cell signalling
  • Pronephros
  • 6-O-endosulfatase
  • Heparan sulfate
  • HSPG
  • Wnt

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