ABSTRACT
Introduction .................................................................................................. 75 Notch signaling cascade ............................................................................. 76 Roles in embryonic vasculatures of zebrafish ........................................ 77 Functions in mammalian embryonic vasculature .................................. 80 Arterial-venous specification in mammals ............................................. 81 Function in mammalian arterial vascular smooth muscle cell differentiation........................................................................................ 83 Function in human vascular disorders .................................................... 84 Conclusions................................................................................................... 85 Acknowledgments ....................................................................................... 86 References...................................................................................................... 86
Introduction Development and maintenance of the cardiovascular system entail multiple cell fate decisions, each of which contributes to the wide array of vascular structures necessary for normal organ function. By modulating the responses of individual cells to environmental cues, the Notch signaling cascade mediates the cell-cell interactions that result in such decisions. The dynamic expression of Notch genes in the vasculature underlies their key function in integrating micro-environmental signals required for the development of arteries, veins, capillaries, and specialized vascular structures. Studies in vertebrates demonstrate that components of the Notch pathway are essential for both developmental angiogenesis and vascular homeostasis. Defective Notch signaling is implicated in human diseases, such as cerebral autosomal
dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and Alagille’s syndrome that are characterized by pathologic vascular degeneration.
