PDF(Pubmed)
Abstract：
Endothelial cells in veins differ in morphology, function and gene expression from those in arteries and lymphatics. Understanding how venous and arterial identities are induced during development is required to understand how arterio-venous malformations occur, and to improve the outcome of vein grafts in surgery by promoting arterialization of veins. To identify factors that promote venous endothelial cell fate in vivo, we isolated veins from quail embryos, at different developmental stages, that were grafted into the coelom of chick embryos. Endothelial cells migrated out from the grafted vein and their colonization of host veins and/or arteries was quantified. We show that venous fate is promoted by sympathetic vessel innervation at embryonic day 11. Removal of sympathetic innervation decreased vein colonization, while norepinephrine enhanced venous colonization. BMP treatment or inhibition of ERK enhanced venous fate, revealing environmental neurotransmitter and BMP signaling and intrinsic ERK inhibition as actors in venous fate acquisition. We also identify the BMP antagonist Noggin as a potent mediator of venous arterialization.
摘要：
静脉中的内皮细胞形态不同，动脉和淋巴管的功能和基因表达。需要了解在发育过程中如何诱导静脉和动脉身份，以了解动静脉畸形是如何发生的。并通过促进静脉动脉化来改善手术中静脉移植的效果。为了确定促进体内静脉内皮细胞命运的因素，我们从鹌鹑胚胎中分离出静脉,在不同的发展阶段，移植到鸡胚的腔室中。内皮细胞从移植静脉迁移出来,并定量它们在宿主静脉和/或动脉中的定植。我们表明，在胚胎第11天时，交感神经血管神经支配会促进静脉命运。去除交感神经支配减少静脉定植，而去甲肾上腺素增强静脉定植。BMP治疗或ERK抑制可增强静脉命运，揭示环境神经递质和BMP信号传导和内在ERK抑制作为静脉命运获取的参与者。我们还确定BMP拮抗剂Noggin是静脉动脉化的有效介质。
