Novel insights into the differential functions of Notch ligands in vascular formation.
Novel insights into the differential functions of Notch ligands in vascular formation.
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DOI：
10.1186/2040-2384-1-8
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发表时间：
2009-11-16
期刊：
影响因子：
--
通讯作者：
Kume T
中科院分区：
文献类型：
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作者：
Kume T
Notch信号通路是发育和疾病中血管形成和形态发生的关键组成部分。令人信服的证据表明，Notch信号是必需的动脉细胞的命运在发展过程中的诱导和选择的内皮细胞的尖端和茎细胞在萌芽血管生成。在哺乳动物中，四种Notch受体中的两种（Notch 1和Notch 4）和五种Notch配体中的三种（Jagged 1、Dll 1和Dll 4）主要在血管内皮细胞中表达，并且对血管生物学的许多方面都很重要。在动脉细胞命运选择和血管生成过程中，Notch 1和Notch 4的作用被认为是相似的，并且Dll 4的功能被充分表征。然而，决定Notch配体在血管内皮细胞中的功能相似性和差异性的分子机制在很大程度上仍然未知;因此，需要进行额外的研究来阐明与血管内皮中Notch激活相关的配体特异性功能和机制。最近的研究结果表明，Dll 1和Dll 4在动脉细胞身份的规范和维护中具有不同的作用，而Dll 4和Jagged 1在萌芽血管生成过程中的尖端和茎细胞选择中具有相反的功能。本文就近年来新发现的Notch配体在血管形成调控中的作用进行综述，并为今后Notch配体在血管形成调控中的研究提供展望。
The Notch signaling pathway is a critical component of vascular formation and morphogenesis in both development and disease. Compelling evidence indicates that Notch signaling is required for the induction of arterial-cell fate during development and for the selection of endothelial tip and stalk cells during sprouting angiogenesis. In mammals, two of the four Notch receptors (Notch1 and Notch4) and three of the five Notch ligands (Jagged1, Dll1, and Dll4) are predominantly expressed in vascular endothelial cells and are important for many aspects of vascular biology. During arterial cell-fate selection and angiogenesis, the roles of Notch1 and Notch4 are thought to be similar, and the function of Dll4 is well-characterized. However, the molecular mechanisms that determine the functional similarities and differences of Notch ligands in vascular endothelial cells remain largely unknown; consequently, additional research is needed to elucidate the ligand-specific functions and mechanisms associated with Notch activation in the vascular endothelium. Results from recent studies indicate that Dll1 and Dll4 have distinct roles in the specification and maintenance of arterial cell identity, while Dll4 and Jagged1 have opposing functions in tip- and stalk-cell selection during sprouting angiogenesis. This review will focus on the newly discovered, distinct functions of several Notch ligands in the regulation of blood vessel formation and will provide perspectives for future research in the field.