Abstract
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.
Highlights
Blood vessel development, which includes vasculogenesis and angiogenesis, is crucial for the formation of the cardiovascular system and blood vessel regeneration after injury
We summarize how spindle orientation regulates endothelial cell division to affect vascular development and discuss the relationship between misorientation and pathological state
During angiogenesis, the asymmetric division of endothelial tip cells generates heterogeneous daughter cells that maintain hierarchical tip-stalk organization and synchronize collective movements (Costa et al, 2016). These processes are closely related to mitotic spindle orientation, which is precisely controlled by many cues, either intrinsic or extrinsic, such as natural direct current electric fields (DC-EFs) and many signaling pathways and proteins that play an important role in spindle orientation including vascular endothelial growth factor (VEGF) signaling, the Rho family of GTPases Cdc42 are indispensable to vascular development and regeneration
Summary
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. Oriented cell division is a vital mechanism in vessel morphogenesis, and defective spindle orientation can perturb the spatial arrangement of daughter cells and contribute to several diseases related to vascular development. Many factors affect endothelial cell proliferation and orientation and blood vessel formation, with the relationship between improper spindle orientation in endothelial cells and various diseases extensively studied. We review the molecular mechanisms driving the orientation of endothelial cell division, with respect to the mitotic spindle, and how these processes affect vascular development, disease pathogenesis, and their potential as novel targets
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