Genetic Analysis of Vascular Development in Zebrafish
The development of the vascular system is one of the earliest events in organogenesis. All other organs depend on a vascular supply for delivery of nutrients, oxygen and cellular and humoral factors, and for clearance of wastes....
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Descripción del proyecto
The development of the vascular system is one of the earliest events in organogenesis. All other organs depend on a vascular supply for delivery of nutrients, oxygen and cellular and humoral factors, and for clearance of wastes. Serious disruptions in the formation of the vascular network are lethal early in post-implantation, while the maintenance of vessel integrity and the control of vessel physiology have important consequences throughout embryonic and adult life. Research carried out over the past years has shed light into the different steps involved in the formation of the vascular system. Genetic evidence has highlighted the roles of many molecules that affect vasculogenesis, angiogenesis and lymphangiogenesis in a complex and tightly regulated manner. Many of the signaling pathways implicated in vascular development are reactivated during disease states of angiogenesis or vessel regression, making a full understanding of the complexities of these pathways important for identifying new targets for therapeutic intervention during pathological situations such as severe tissue ischemia, coronary heart disease, lymphedema and tumor promoted angiogenesis and lymphangiogenesis.
The objective of this proposal is to use the accessible zebrafish embryo, which has a well-described, stereotypical vertebrate vasculature, to identify and characterize novel players involved in the formation of blood and lymphatic vessels. The strength of our approach lies in our ability to combine unique in vivo assays, powerful genetic tools, and sophisticated long term imaging of living embryos. As most developmental processes are remarkably similar between zebrafish and humans, both in molecular aspects and function, these studies are likely to reveal conserved pathways regulating the development and function of blood and lymphatic endothelial cells in humans.