Syntenin, a syndecan adaptor and an Arf6 phosphatidylinositol 4,5-bisphosphate effector, is essential for epiboly and gastrulation cell movements in zebrafish
Syntenin, a syndecan adaptor and an Arf6 phosphatidylinositol 4,5-bisphosphate effector, is essential for epiboly and gastrulation cell movements in zebrafish
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DOI：
10.1242/jcs.089987
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发表时间：
2012-03-01
影响因子：
4
通讯作者：
Zimmermann, Pascale
中科院分区：
文献类型：
--
作者：
Lambaerts, Kathleen;Van Dyck, Stijn;Zimmermann, Pascale
在鱼类胚胎中，胚胎层的展开和变薄以覆盖卵黄细胞并关闭胚孔，是原肠形成过程的中心。尽管它很重要，但人们对控制这种协调的细胞运动的分子机制知之甚少。通过对斑马鱼(Danio Rerio)的击倒研究和挽救实验的结合，我们发现胚珠依赖于Syntenin和Syndecan Heparan Sulate蛋白多糖的分子网络，Syndecan Heparan Sulate蛋白多糖作为黏附分子和生长因子的共同受体。此外，我们还发现Syntenin与磷脂酰肌醇4，5-二磷酸(PIP2)以及调节Syndecan内吞循环的小GTP酶ADP-核糖化因子6(Arf6)之间的相互作用是上胚层发育所必需的。对最早的细胞缺陷的分析表明，Syntenin在卵黄合胞层的自主植物扩张和胚胎外组织中肌动蛋白细胞骨架的重排中发挥了作用，但在决定胚胎细胞命运方面没有作用。本研究确定了Syntenin-Syndecan-PIP2-Arf6复合体在鱼类胚珠发育过程中的重要性，并确定了其在早期发育中定向细胞运动中的关键作用。
Epiboly, the spreading and the thinning of the blastoderm to cover the yolk cell and close the blastopore in fish embryos, is central to the process of gastrulation. Despite its fundamental importance, little is known about the molecular mechanisms that control this coordinated cell movement. By a combination of knockdown studies and rescue experiments in zebrafish (Danio rerio), we show that epiboly relies on the molecular networking of syntenin with syndecan heparan sulphate proteoglycans, which act as co-receptors for adhesion molecules and growth factors. Furthermore, we show that the interaction of syntenin with phosphatidylinositol 4,5-bisphosphate (PIP2) and with the small GTPase ADP-ribosylation factor 6 (Arf6), which regulate the endocytic recycling of syndecan, is necessary for epiboly progression. Analysis of the earliest cellular defects suggests a role for syntenin in the autonomous vegetal expansion of the yolk syncytial layer and the rearrangement of the actin cytoskeleton in extra-embryonic tissues, but not in embryonic cell fate determination. This study identifies the importance of the syntenin-syndecan-PIP2-Arf6 complex for the progression of fish epiboly and establishes its key role in directional cell movements during early development.