sonic hedgehog and vascular endothelial growth factor act upstream of the notch pathway during arterial endothelial differentiation
sonic hedgehog and vascular endothelial growth factor act upstream of the notch pathway during arterial endothelial differentiation
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DOI：
10.1016/s1534-5807(02)00198-3
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发表时间：
2002-07-01
影响因子：
11.8
通讯作者：
Weinstein, BM
中科院分区：
文献类型：
--
作者：
Lawson, ND;Vogel, AM;Weinstein, BM
动脉和静脉内皮细胞在循环前的分子差异表明，遗传因素决定了这些细胞类型。我们发现，血管内皮生长因子（vegf）的行为下游的音刺猬（shh）和上游的缺口途径，以确定动脉细胞的命运。VEGF或Shh的缺失导致动脉身份的丧失，而这些因子的外源性表达导致动脉标志物的异位表达。将VEGF mRNA显微注射到缺乏Shh活性的胚胎中可以挽救动脉分化。最后，在缺乏VEGF信号传导的情况下Notch途径的激活可以挽救动脉标志物基因表达。这些研究揭示了一个复杂的信号级联负责建立动脉细胞的命运，并提出了不同的影响VEGF对发展中的内皮细胞。
The appearance of molecular differences between arterial and venous endothelial cells before circulation suggests that genetic factors determine these cell types. We find that vascular endothelial growth factor (vegf) acts downstream of sonic hedgehog (shh) and upstream of the Notch pathway to determine arterial cell fate. Loss of Vegf or Shh results in loss of arterial identity, while exogenous expression of these factors causes ectopic expression of arterial markers. Microinjection of vegf mRNA into embryos lacking Shh activity can rescue arterial differentiation. Finally, activation of the Notch pathway in the absence of Vegf signaling can rescue arterial marker gene expression. These studies reveal a complex signaling cascade responsible for establishing arterial cell fate and suggest differential effects of Vegf on developing endothelial cells.