Suppression of Notch signalling by the COUP-TFII transcription factor regulates vein identity
Suppression of Notch signalling by the COUP-TFII transcription factor regulates vein identity
复制标题
DOI：
10.1038/nature03511
复制
发表时间：
2005-05-05
期刊：
影响因子：
64.8
通讯作者：
Tsai, SY
中科院分区：
文献类型：
--
作者：
You, LR;Lin, FJ;Tsai, SY
动脉和静脉在解剖学上、功能上和分子上是不同的。目前的动脉-静脉同一性模型提出，血管内皮生长因子与其异二聚体受体-Flk 1和神经纤毛蛋白1（NP-1;也称为Nrp 1）-的结合激活内皮中的Notch信号传导途径，引起肝配蛋白B2表达的诱导和肝配蛋白受体B4表达的抑制，以建立动脉同一性（1-4）。关于静脉身份知之甚少，除了它涉及肝配蛋白受体B4表达，因为Notch信号在静脉中不被激活;一个未解决的问题是静脉身份是如何调节的。在这里，我们表明，COUP-TFII（也称为Nr 2f 2），孤儿核受体超家族的成员，是专门表达在静脉，但不是动脉内皮。内皮细胞中COUP-TFII的消融使静脉能够获得动脉特征，包括动脉标志物NP-1和Notch信号传导分子的表达，以及造血细胞簇的产生。此外，COUP-TFII在内皮细胞中的异位表达导致转基因小鼠胚胎中静脉和动脉的融合。因此，COUP-TFII在抑制Notch信号传导以维持静脉身份方面具有关键作用，这表明静脉身份受遗传控制，并且不是由默认途径衍生的。
Arteries and veins are anatomically, functionally and molecularly distinct. The current model of arterial - venous identity proposes that binding of vascular endothelial growth factor to its heterodimeric receptor - Flk1 and neuropilin 1 (NP-1; also called Nrp1) - activates the Notch signalling pathway in the endothelium, causing induction of ephrin B2 expression and suppression of ephrin receptor B4 expression to establish arterial identity(1-4). Little is known about vein identity except that it involves ephrin receptor B4 expression, because Notch signalling is not activated in veins; an unresolved question is how vein identity is regulated. Here, we show that COUP-TFII ( also known as Nr2f2), a member of the orphan nuclear receptor superfamily, is specifically expressed in venous but not arterial endothelium. Ablation of COUP-TFII in endothelial cells enables veins to acquire arterial characteristics, including the expression of arterial markers NP-1 and Notch signalling molecules, and the generation of haematopoietic cell clusters. Furthermore, ectopic expression of COUP-TFII in endothelial cells results in the fusion of veins and arteries in transgenic mouse embryos. Thus, COUP-TFII has a critical role in repressing Notch signalling to maintain vein identity, which suggests that vein identity is under genetic control and is not derived by a default pathway.