A New Conserved Player in Lymphatic Morphogenesis.

The lymphatic system comprises a network of interconnected and blind-ended vessels whose central function is to maintain fluid homeostasis. Similar to the vessels of the circulatory system, the lymphatic system consists of a hierarchical network of small and large caliber vessels, which function together to allow fluid drainage. Lymphatic capillaries are lined by endothelial cells that are highly discontinuous, making them permeable to surrounding fluid to facilitate resorption. By contrast, larger lymphatic collecting ducts possess a thin smooth muscle layer and valves to promote unidirectional transport of fluid toward connection points with the circulatory system at the subclavian veins. In addition to fluid homeostasis, the lymphatic system and the constituent lymph nodes are a portal for lymphocytes, as well as antigenpresenting cells, while also functioning in lipid absorption in the digestive system. Given their wide-ranging importance in these normal physiological processes, it is not surprising that the lymphatic system is implicated in several pathological conditions. Indeed, inflammation is intimately associated with lymphatic function and is a central cause of lymphedema in a wide range of acquired and congenital diseases. Notably, congenital forms of lymphedema are associated with mutations in several genes important for lymphatic vessel formation, including those encoding the receptor tyrosine kinase FLT4 and its ligand, VEGFC.