Department of Biology, University of York, York YO10 5YW, UK.
Dev Biol. 2010 May 15;341(2):375-88. doi: 10.1016/j.ydbio.2010.02.034. Epub 2010 Mar 4.
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.
在脊椎动物中,有两个相关基因,Sulf1 和 Sulf2,它们编码细胞外肝素硫酸 6-O-内切硫酸酯酶。这些酶在后合成过程中重塑肝素硫酸链,产生细胞表面 HSPG 的结构多样性;这种活性提供了调节发育细胞信号的重要机制。在这里,我们描述了 Xenopus tropicalis Sulf2(XtSulf2)的表达和活性,它与 XtSulf1 一样,可以在细胞外发挥作用,抑制 BMP4 和 FGF4 信号。与其在发育中神经前区域的离散表达一致,我们发现 XtSulf2 的过表达会破坏一组神经标记物的表达,并抑制神经嵴的迁移。我们使用 Xenopus 胚胎的移植实验和基于反义 morpholino 的敲低研究的组合,证明内源性 XtSulf1 和 XtSulf2 在体内颅神经嵴细胞迁移中发挥重要作用。