Notch signaling in vascular morphogenesis

PURPOSE OF REVIEW: This review highlights recent developments in the role of the Notch signaling pathway during vascular morphogenesis, angiogenesis, and vessel homeostasis. RECENT FINDINGS: Studies conducted over the past 4 years have significantly advanced the understanding of the effect of Notch signaling on vascular development. Major breakthroughs have elucidated the role of Notch in arterial versus venular specification and have placed this pathway downstream of vascular endothelial growth factor. SUMMARY: An emerging hallmark of the Notch signaling pathway is its nearly ubiquitous participation in cell fate decisions that affect several tissues, including epithelial, neuronal, hematopoietic, and muscle. The vascular compartment has been the latest addition to the list of tissues known to be regulated by Notch. Unraveling the contribution of Notch signaling to blood vessel formation has resulted principally from gain-of-function and loss-of-function experiments in mouse and zebrafish. During the past 4 years, these mechanistic studies have revealed that Notch is required for the successful completion of several steps during vascular morphogenesis and differentiation. In addition, the findings that Notch mutations are linked to some late-onset hereditary vascular pathologic conditions suggest the added contribution of this signaling pathway to vascular homeostasis.