Alva Jackelyn A, Iruela-Arispe M Luisa
Department of Molecular, Cell, and Developmental Biology and Molecular Biology Institute, UCLA, Los Angeles, California 90095, USA.
Curr Opin Hematol. 2004 Jul;11(4):278-83. doi: 10.1097/01.moh.0000130309.44976.ad.
This review highlights recent developments in the role of the Notch signaling pathway during vascular morphogenesis, angiogenesis, and vessel homeostasis.
Studies conducted over the past 4 years have significantly advanced the understanding of the effect of Notch signaling on vascular development. Major breakthroughs have elucidated the role of Notch in arterial versus venular specification and have placed this pathway downstream of vascular endothelial growth factor.
An emerging hallmark of the Notch signaling pathway is its nearly ubiquitous participation in cell fate decisions that affect several tissues, including epithelial, neuronal, hematopoietic, and muscle. The vascular compartment has been the latest addition to the list of tissues known to be regulated by Notch. Unraveling the contribution of Notch signaling to blood vessel formation has resulted principally from gain-of-function and loss-of-function experiments in mouse and zebrafish. During the past 4 years, these mechanistic studies have revealed that Notch is required for the successful completion of several steps during vascular morphogenesis and differentiation. In addition, the findings that Notch mutations are linked to some late-onset hereditary vascular pathologic conditions suggest the added contribution of this signaling pathway to vascular homeostasis.
本综述重点介绍Notch信号通路在血管形态发生、血管生成和血管稳态过程中的作用的最新进展。
过去4年进行的研究显著推进了对Notch信号对血管发育影响的理解。重大突破阐明了Notch在动脉与静脉特化中的作用,并将该信号通路置于血管内皮生长因子下游。
Notch信号通路的一个新特点是它几乎普遍参与影响多种组织(包括上皮、神经元、造血和肌肉组织)的细胞命运决定。血管部分是已知受Notch调节的组织名单中的最新成员。阐明Notch信号对血管形成的贡献主要源于在小鼠和斑马鱼中进行的功能获得和功能丧失实验。在过去4年中,这些机制研究表明,Notch是血管形态发生和分化过程中成功完成几个步骤所必需的。此外,Notch突变与一些迟发性遗传性血管病理状况相关的发现表明该信号通路对血管稳态也有额外贡献。