Program in Genomics of Differentiation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Department of Cell and Developmental Biology, University College London, London WC1E 6BT, United Kingdom.
Dev Biol. 2014 Jun 15;390(2):116-25. doi: 10.1016/j.ydbio.2014.03.018. Epub 2014 Mar 31.
Initial embryonic determination of artery or vein identity is regulated by genetic factors that work in concert to specify the endothelial cell׳s (EC) fate, giving rise to two structurally unique components of the circulatory loop. The Shh/VEGF/Notch pathway is critical for arterial specification, while the orphan receptor nr2f2 (COUP-TFII) has been implicated in venous specification. Studies in mice have shown that nr2f2 is expressed in venous but not arterial ECs, and that it preferentially induces markers of venous cell fate. We have examined the role of nr2f2 during early arterial-venous development in the zebrafish trunk. We show that expression of a subset of markers of venous endothelial identity requires nr2f2, while the expression of nr2f2 itself requires sox7 and sox18 gene function. However, while sox7 and sox18 are expressed in both the cardinal vein and the dorsal aorta during early trunk development, nr2f2 is expressed only in the cardinal vein. We show that Notch signaling activity present in the dorsal aorta suppresses expression of nr2f2, restricting nr2f2-dependent promotion of venous differentiation to the cardinal vein.
动脉或静脉身份的初始胚胎决定受遗传因素的协调调节，这些遗传因素决定了内皮细胞（EC）的命运，形成循环回路的两个结构独特的组成部分。Shh/VEGF/Notch 通路对于动脉特化至关重要，而孤儿受体 nr2f2（COUP-TFII）已被牵连到静脉特化中。在小鼠中的研究表明，nr2f2 在静脉而不是动脉 EC 中表达，并且它优先诱导静脉细胞命运的标志物。我们已经在斑马鱼躯干中检查了 nr2f2 在早期动静脉发育过程中的作用。我们表明，一组静脉内皮特征标志物的表达需要 nr2f2，而 nr2f2 本身的表达需要 sox7 和 sox18 基因功能。然而，虽然 sox7 和 sox18 在早期躯干发育过程中都在心脏静脉和背主动脉中表达，但 nr2f2 仅在心脏静脉中表达。我们表明，存在于背主动脉中的 Notch 信号活性抑制了 nr2f2 的表达，将 nr2f2 依赖性促进静脉分化限制在心脏静脉中。
