Laboratory of Developmental Signaling, VIB Center for the Biology of Disease, VIB, 3000 Leuven, Belgium.
Trends Genet. 2013 Mar;29(3):140-9. doi: 10.1016/j.tig.2012.11.008. Epub 2012 Dec 30.
Vascular patterning involves sprouting of blood vessels, which is governed by orchestrated communication between cells in the surrounding tissue and endothelial cells (ECs) lining the blood vessels. Single ECs are selected for sprouting by hypoxia-induced stimuli and become the 'tip' or leader cell that guides new sprouts. The 'stalk' or trailing ECs proliferate for tube extension and lumenize the nascent vessel. Stalk and tip cells can dynamically switch their identities during this process in a Notch-dependent manner. Here, we review recent studies showing that bone morphogenetic protein (BMP) signaling coregulates Notch target genes in ECs. In particular, we focus on how Delta-like ligand 4 (DLL4)-Notch and BMP effector interplay may drive nonsynchronized oscillatory gene expression in ECs essential for setting sharp tip-stalk cell boundaries while sustaining a dynamic pool of nonsprouting ECs. Deeper knowledge about the coregulation of vessel plasticity in different vascular beds may result in refinement of anti-angiogenesis and vessel normalization therapies.
血管模式形成涉及血管的出芽,这是由周围组织细胞和血管内皮细胞(EC)之间协调的通讯控制的。单个 EC 被缺氧诱导的刺激选择进行出芽,并成为引导新出芽的“尖端”或先导细胞。“茎干”或尾随 EC 增殖以延长管腔并使新生血管管腔化。在这个过程中,茎干和尖端细胞可以以 Notch 依赖的方式动态切换它们的身份。在这里,我们回顾了最近的研究表明,骨形态发生蛋白(BMP)信号在 EC 中共同调节 Notch 靶基因。特别是,我们关注的是 Delta-like 配体 4(DLL4)-Notch 和 BMP 效应子相互作用如何驱动 EC 中必不可少的非同步振荡基因表达,为设置尖锐的尖端-茎干细胞边界提供动力,同时维持动态的非出芽 EC 池。对不同血管床中血管可塑性的共同调控的更深了解可能会导致抗血管生成和血管正常化治疗的改进。