Figure 1.

Development of lymphatics. (a) In response to unknown factors, lymphatic differentiation is initiated by the polarized expression of Sox18 (yellow nuclei) in venous endothelium. (b) Subsequently, Sox18 causes Prox1 expression (brown nuclei) leading to the exodus of lymphatic progenitors (yellow cells) from the cardinal veins and the formation of primary lymph sacs at distant sites. (c) Sox18 expression subsides, but Prox1 expression is maintained in lymphatic endothelium, and lymphatics form by sprouting from the primitive lymph sacs. (d) Genetic ablation of Prox1 from lymphatic endothelium results in dedifferentiation. Lymphatic-specific proteins are lost, whereas blood-vessel-specific proteins are re-expressed (magenta). Blood enters the lymphatics via aberrant connections, which could be caused by fusion of adjacent vessels (white arrow) or sprouting angiogenesis (grey arrow).