Abstract
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 language | English |
|---|---|
| Pages (from-to) | 1408-1421 |
| Number of pages | 14 |
| Journal | Journal of Cell Science |
| Volume | 128 |
| Issue number | 7 |
| Early online date | 13 Feb 2015 |
| DOIs | |
| Publication status | Published - 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 (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.Keywords
- Morphogen
- Development
- Cell signalling
- Pronephros
- 6-O-endosulfatase
- Heparan sulfate
- HSPG
- Wnt
