Heparan sulfate proteoglycans (HSPGs) are synthesised and modified in the Golgi before they are presented at the cell surface. Modifications include the addition of sulfate groups at specific positions on sugar residues along the heparan sulfate (HS) chain which results in a structural heterogeneity that underpins the ability of HSPGs to bind with high affinity to many different proteins, including growth factors and their receptors. Sulf1 codes for a 6-0-endosulfatase that is present and active extracellularly, providing a further mechanism to generate structural diversity through the post-synthetic remodelling of HS. Here we use Xenopus embryos to demonstrate in vivo that Xtsulf1 plays an important role in modulating cell signaling during development. We show that while XtSulf1 can enhance the axis-inducing activity of Wnt11, XtSulf1 acts during embryogenesis to restrict BMP and FGF signaling.

In vertebrates, there are two related genes, Sulf1 and Sulf2 that code for extracellular heparan sulphate 6-0-endosulphatases. These enzymes act to post-synthetically remodel heparan sulphate chains, generating structural diversity of cell surface HSPGs; this activity provides an important mechanism to modulate developmental cell signalling. Here we describe the expression and activity of Xenopus tropicalis Sulf2 (XtSulf2), which like XtSulf1, can act extracellularly to inhibit BMP4 and FGF4 signalling. Consistent with its discrete expression in regions of the anterior developing nervous system, we found that overexpression of XtSulf2 disrupts the expression of a set of neural markers and inhibits the migration of the neural crest. Using a combination of grafting experiments and antisense morpholino based knockdown studies in Xenopus embryos, we demonstrate that endogenous XtSulf1 and XtSulf2 play an important role during cranial neural crest cell migration in vivo.