The lymphatic system is composed of a hierarchy of vessels with specific features serving their unique functions: the blind-ended lymphatic capillaries that absorb the interstitial fluid and the collecting lymphatic vessels that transport the lymph to the cardiovascular system. Failure of the lymphatic vessels, caused by a genetic defect (primary) or damage following surgery or radiation therapy (secondary) can lead to lymphoedema, which is a progressive and lifelong condition characterised by gross swelling of the affected tissue. Notably, several primary lymphoedemas are characterised by defects that affect specifically either the collecting vessels or the capillaries. In addition, specific area(s) of the body are affected in different types of lymphoedemas. What underlies tissue-specific vessel failure is not understood yet this knowledge is instrumental in designing therapeutic strategies for lymphoedema and other lymphatic disorders that are currently lacking. In this project we will identify genes and mechanisms required for organ-specific lymphatic vascular development by characterising the features of specific lymphatic vascular beds, and by identifying and functionally characterising genes regulating lymphatic development in an organ- and/or vessel-type specific manner using genetic mouse models.

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