Development of the mammalian lymphatic vasculature is a stepwise process requiring the specification of lymphatic endothelial cell progenitors in the embryonic veins, and their subsequent budding to give rise to most of the mature lymphatic vasculature. In mice, formation of the lymphatic vascular network starts inside the cardinal vein at around E9.5 when a subpopulation of venous endothelial cells get committed into the lymphatic lineage by their acquisition of Prox1 expression. Here we will continue with our long-time efforts to accomplish a detailed cellular and molecular characterization of the genes and mechanisms regulating the early steps leading to the formation of the mammalian lymphatic vasculature. A better understanding of basic aspects of early lymphatic development and the availability of novel tools and animal models has been instrumental in the identification of important novel functional roles of the lymphatic vasculature.
Here we propose to identify and characterize new candidate genes participating in early stages of lymphatic development, provide novel clues about the role of energy and mitochondria in LEC specification and differentiation, and characterize the processes of lymphatic tube and lumen formation. This knowledge will help us gain a better understanding of most key aspects regulating developmental lymphangiogenesis and provide additional clues on genes and mechanisms responsible for functional defects leading to lymphatic malfunction. This knowledge will facilitate the treatment of pathological conditions such as inflammation, autoimmunity, cancer, metabolic disorders, and maybe even neurological diseases that could all be consequence of a defective or somehow impaired lymphatic vasculature.
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