Hirashima Masanori, Suda Toshio
The Sakaguchi Laboratory of Developmental Biology, School of Medicine, Keio University, Tokyo, Japan.
Endothelium. 2006 Mar-Apr;13(2):137-45. doi: 10.1080/10623320600698078.
The vascular system is comprised of an organized hierarchical structure of arteries, veins, and capillaries. Recent studies in zebrafish, chick, and mouse reveal that the identity of artery and vein is governed by genetic factors as well as blood flow. The ephrin/Eph system establishes arterial and venous endothelial cell identity, and is important for structural segregation between arteries and veins. Analyses using loss- or gain-of-function mutations in zebrafish and mice show that Su(H)/RBP-J-dependent Delta/Notch signaling is a key mediator of arterial endothelial cell fate decision and vascular patterning. Vascular endothelial growth factor has also been shown to work upstream of Notch and is a key player in arteriogenesis. On the other hand, an orphan nuclear receptor, COUP-TFII, induces venous endothelial cell differentiation by suppressing the Notch signaling. Arteriovenous malformations are frequently induced by a loss of arterial and venous cell specification. These insights indicate that the balance of these genetic factors and modification by epigenetic factors such as hemodynamics and oxygen tension are important for proper endothelial cell identities in vascular morphogenesis.
血管系统由动脉、静脉和毛细血管组成的有组织的层次结构构成。最近在斑马鱼、鸡和小鼠身上的研究表明，动脉和静脉的特性受遗传因素以及血流的支配。 Ephrin/Eph系统确立了动脉和静脉内皮细胞的特性，并且对于动脉和静脉之间的结构分隔很重要。利用斑马鱼和小鼠的功能丧失或功能获得突变进行的分析表明，Su(H)/RBP-J依赖的Delta/Notch信号传导是动脉内皮细胞命运决定和血管模式形成的关键介质。血管内皮生长因子也已被证明在Notch上游起作用，并且是动脉生成中的关键参与者。另一方面，一种孤儿核受体COUP-TFII通过抑制Notch信号传导诱导静脉内皮细胞分化。动静脉畸形经常由动脉和静脉细胞特异性的丧失所诱导。这些见解表明，这些遗传因素的平衡以及诸如血流动力学和氧张力等表观遗传因素的修饰对于血管形态发生中适当的内皮细胞特性很重要。
