Wu Xuemei, Zhou Jun, Li Dengwen
State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China.
Shandong Provincial Key Laboratory of Animal Resistance Biology, Collaborative Innovation Center of Cell Biology in Universities of Shandong, College of Life Sciences, Institute of Biomedical Sciences, Shandong Normal University, Jinan, China.
Front Cell Dev Biol. 2020 Sep 17;8:583325. doi: 10.3389/fcell.2020.583325. eCollection 2020.
Angiogenesis requires coordinated endothelial cell specification, proliferation, and collective migration. The orientation of endothelial cell division is tightly regulated during the earliest stages of blood vessel formation in response to morphogenetic cues and the controlled orientation of the mitotic spindle. Consequently, oriented cell division is a vital mechanism in vessel morphogenesis, and defective spindle orientation can perturb the spatial arrangement of daughter cells and consequently contribute to several diseases related to vascular development. Many factors affect endothelial cell proliferation and orientation and therefore blood vessel formation, with the relationship between improper spindle orientation in endothelial cells and various diseases extensively studied. Here we review the molecular mechanisms driving the orientation of endothelial cell division, particularly with respect to the mitotic spindle, and how these processes affect vascular development, disease pathogenesis, and their potential as novel targets.
血管生成需要内皮细胞的特化、增殖和集体迁移协调进行。在血管形成的最早阶段,内皮细胞分裂的方向会根据形态发生线索和有丝分裂纺锤体的可控方向受到严格调控。因此,定向细胞分裂是血管形态发生中的一个重要机制,纺锤体定向缺陷会扰乱子细胞的空间排列,进而导致多种与血管发育相关的疾病。许多因素会影响内皮细胞的增殖和定向,从而影响血管生成,内皮细胞中纺锤体定向不当与各种疾病之间的关系已得到广泛研究。在这里,我们综述了驱动内皮细胞分裂定向的分子机制,特别是关于有丝分裂纺锤体的机制,以及这些过程如何影响血管发育、疾病发病机制,以及它们作为新靶点的潜力。