Molecular lymphangiogenesis: new players

The function of the lymphatic vascular system as a conduit for immune cells and excess tissue fluid has been known for over a century, but the molecular players involved in lymphangiogenesis--the formation of lymphatic vessels--have remained unknown until recently. Signals mediated by vascular endothelial growth factor-C, the homeodomain transcription factor PROX1 and the forkhead transcription factor FOXC2 have been implicated in the growth, morphogenesis and hierarchic organization of the lymphatic vascular network. Recent results have also shown the importance of the angiopoietin-Tie and ephrin-Eph signaling systems in lymphangiogenesis, suggesting that these pathways regulate the lymphatic vascular system in a manner similar to, yet distinct from, their regulation of angiogenesis. This review provides an overview of the molecular players involved in lymphangiogenesis, with special emphasis on recently discovered molecular mechanisms.