LIGAND-DEPENDENT NOTCH SIGNALING IN VASCULAR FORMATION
LIGAND-DEPENDENT NOTCH SIGNALING IN VASCULAR FORMATION
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DOI：
10.1007/978-1-4614-0899-4_16
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发表时间：
2012-01-01
期刊：
影响因子：
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通讯作者：
Kume, Tsutomu
中科院分区：
文献类型：
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作者：
Kume, Tsutomu
Notch信号通路是发育和疾病中血管形成和形态发生的重要组成部分。令人信服的证据表明，Notch信号是发育过程中动脉细胞命运的诱导以及血管新生过程中内皮尖端和柄细胞的选择所必需的。在哺乳动物中，四种Notch受体中的两种（Notchl和Notch4）和五种Notch配体中的三种（Jaggedl、D111和D114）主要在血管内皮细胞中表达，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，Notchl和Notch4的作用被认为是相似的，D114的作用也得到了很好的表征。然而，决定Notch配体在血管内皮细胞中功能异同的分子机制在很大程度上仍然未知；因此，需要进一步的研究来阐明与Notch在血管内皮中激活相关的配体特异性功能和机制。最近的研究结果表明，Dill和D114在动脉细胞身份的规范和维持中具有不同的作用，而D114和Jagged I在发芽血管生成过程中对尖端和柄细胞的选择具有相反的作用。本章将重点介绍新发现的几种Notch配体在血管形成调控中的独特作用，并为该领域的未来研究提供观点。
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 (Notchl and Notch4) and three of the five Notch ligands (Jaggedl, D111 and D114) 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 Notchl and Notch4 are thought to be similar and the role of D114 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 Dill and D114 have distinct roles in the specification and maintenance of arterial cell identity, while D114 and Jagged I have opposing effects on tip- and stalk-cell selection during sprouting angiogenesis. This chapter will focus on the newly discovered, distinct roles of several Notch ligands in the regulation of blood vessel formation and will provide perspectives for future research in the field.