Shawber Carrie J, Kitajewski Jan
Department of Pathology and OB/GYN, Columbia University, USA.
Bioessays. 2004 Mar;26(3):225-34. doi: 10.1002/bies.20004.
Vascular development entails multiple cell-fate decisions to specify a diverse array of vascular structures. Notch proteins are signaling receptors that regulate cell-fate determination in a variety of cell types. The finding that Notch genes are robustly expressed in the vasculature suggests roles for Notch in guiding endothelial and associated mural cells through the myriad of cell-fate decisions needed to form the vasculature. In fact, mice with defects in genes encoding Notch, Notch ligands, and components of the Notch signaling cascade invariably display vascular defects. Human Notch genes are linked to Alagille's Syndrome, a developmental disorder with vascular defects, and CADASIL, a cerebral arteriopathy. Studies in zebrafish, mice and humans indicate that Notch works in conjunction with other angiogenic pathways to pattern and stabilize the vasculature. Here, we will focus on established functions for Notch in vascular remodeling and arterial/venous specification and more speculative roles in vascular homeostasis and organ-specific angiogenesis.
血管发育需要进行多种细胞命运决定，以形成多种多样的血管结构。Notch蛋白是信号受体，可调节多种细胞类型中的细胞命运决定。Notch基因在脉管系统中强烈表达这一发现表明，Notch在引导内皮细胞和相关壁细胞做出形成脉管系统所需的众多细胞命运决定中发挥作用。事实上，编码Notch、Notch配体和Notch信号级联成分的基因存在缺陷的小鼠总是表现出血管缺陷。人类Notch基因与伴有血管缺陷的发育障碍阿拉吉耶综合征以及一种脑动脉病——伴有皮质下梗死和白质脑病的常染色体显性遗传性脑动脉病（CADASIL）相关。对斑马鱼、小鼠和人类的研究表明，Notch与其他血管生成途径协同作用，以构建脉管系统并使其稳定。在此，我们将重点关注Notch在血管重塑和动脉/静脉特化方面已确定的功能，以及在血管稳态和器官特异性血管生成方面更具推测性的作用。
