A unique role for 6-O sulfation modification in zebrafish vascular development
A unique role for 6-O sulfation modification in zebrafish vascular development
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DOI：
10.1016/j.ydbio.2005.05.032
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发表时间：
2005-08-15
影响因子：
2.7
通讯作者：
Ekker, SC
中科院分区：
文献类型：
--
作者：
Chen, E;Stringer, SE;Ekker, SC
硫酸乙酰肝素蛋白聚糖是多种模式化过程中生长因子信号传导的重要调节剂。在血管生成中起关键作用的分泌的生长因子与硫酸乙酰肝素结合，并且这种结合受到硫酸乙酰肝素链的6-O-硫酸化的影响。此外，6-O-硫酸酯是由一个家庭的磺基转移酶（HS 6ST）催化，和遗传操纵它们的功能允许评估其对血管组装的贡献。我们报告的生化活性和表达模式的两个斑马鱼HS 6ST基因。原位杂交揭示了这两个基因在发育过程中的动态和不同的表达模式。来自野生型和吗啉代反义“敲低”胚胎的硫酸乙酰肝素的结构分析表明，HS 6ST-1和HS 6ST-2具有相似的生物化学活性。HS 6ST-2，但不是HS 6ST-1，morphants表现出异常的尾静脉在胚胎发育过程中的分支形态发生。我们的发现，HS 6ST-2所需的尾静脉的分支形态发生是第一个在体内的证据，在脊椎动物血管生成的硫酸乙酰肝素修饰酶的基因编码的一个重要作用。我们对两个斑马鱼HS 6ST基因的分析表明，脊椎动物基因组中的一系列硫酸化修饰酶可能会调节广泛的生物过程。(c)2005年爱思唯尔公司All rights reserved.
Heparan sulfate proteoglycans are important modulators of growth factor signaling in a variety of patterning processes. Secreted growth factors that play critical roles in angiogenesis bind to heparan sulfate, and this association is affected by 6-O-sulfation of the heparan sulfate chains. Addition of 6-O-sulfate is catalyzed by a family of sulfotransferases (HS6STs), and genetic manipulation of their function permits an assessment of their contribution to vascular assembly. We report on the biochemical activity and expression patterns of two zebrafish HS6ST genes. In situ hybridization reveals dynamic and distinct expression patterns of these two genes during development. Structural analysis of heparan sulfate from wild-type and morpholino antisense 'knockdown' embryos suggests that HS6ST-1 and HS6ST-2 have similar biochemical activity. HS6ST-2, but not HS6ST-1, morphants exhibit abnormalities in the branching morphogenesis of the caudal vein during embryonic development of the zebrafish. Our finding that HS6ST-2 is required for the branching morphogenesis of the caudal vein is the first in vivo evidence for an essential role of a gene encoding a heparan sulfate modifying enzyme in vertebrate angiogenesis. Our analysis of two zebrafish HS6ST genes suggests that a wide range of biological processes may be regulated by an array of sulfation-modifying enzymes in the vertebrate genome. (c) 2005 Elsevier Inc. All rights reserved.