Core fucosylation is required for midline patterning during zebrafish development.
Core fucosylation is required for midline patterning during zebrafish development.
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DOI：
10.1002/dvdy.22475
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发表时间：
2010-12
影响因子：
2.5
通讯作者：
Shur, Barry D.
中科院分区：
文献类型：
--
作者：
Seth, Anandita;Machingo, Quentin J.;Fritz, Andreas;Shur, Barry D.
复杂的碳水化合物代表了一类最具多态的大分子，但它们在胚胎发育期间的功能仍未得到很好的确定。在这里，我们证明了在斑马鱼发育过程中，负责将α1，6岩藻糖基残基添加到N-连接寡糖核心区的岩藻糖基转移酶FucT8的敲除导致了斑马鱼发育过程中中线图案的缺陷。FucT8的表达减少会导致轻度的睫状视、小的前脑、U形体节以及其他中线图案缺陷。FucT8的主要底物之一被鉴定为载脂蛋白B(ApoB)，它是脊椎动物中负责组装和分泌脂蛋白颗粒的主要支架蛋白。在果蝇中，脂蛋白颗粒被认为通过作为脂质修饰的细胞信号蛋白的运输工具来促进细胞信号传递，如刺猬。在这方面，ApoB在斑马鱼胚胎中的表达下调导致了与FucT8变形胚胎中类似的中线图案缺陷。此外，初步研究表明，ApoB促进了斑马鱼发育过程中的Sonic Hedgehog信号传递，类似于果蝇中脂蛋白颗粒在Hedgehog信号传递过程中的作用。
Complex carbohydrates represent one of the most polymorphic classes of macromolecules, but their functions during embryonic development remain poorly defined. Herein, we show that knockdown of FucT8, the fucosyltransferase responsible for adding an α1,6 fucosyl residue to the core region of N-linked oligosaccharides, results in defective midline patterning during zebrafish development. Reduced FucT8 expression leads to mild cyclopia, small forebrains, U-shaped somites, among other midline patterning defects. One of the principal FucT8 substrates was identified as Apolipoprotein B (ApoB), the major scaffold protein that is responsible for assembly and secretion of lipoprotein particles in vertebrates. In Drosophila, lipoprotein particles are thought to facilitate cell signaling by serving as a transport vehicle for lipid-modified cell signaling proteins, such as hedgehog. In this regard, knockdown of ApoB expression in zebrafish embryos leads to similar midline patterning defects as those seen in FucT8 morphant embryos. Furthermore, preliminary studies suggest that ApoB facilitates Sonic hedgehog signaling during zebrafish development, analogous to the function of lipoprotein particles during hedgehog signaling in Drosophila.
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