FOXC2 transcription factor: a novel regulator of lymphangiogenesis

Lymphangiogenesis is the critical process of forming new lymphatic vessels under physiological and pathological conditions and involves both molecular and morphological changes. Despite evidence that lymphangiogenic factors, including vascular endothelial growth factors (VEGFs) and Prox1, regulate lymphangiogenesis, the molecular mechanisms underlying gene regulation in lymphatic vessel remodeling and maturation are not fully understood. Importantly, recent studies demonstrate that Forkhead transcription factor FOXC2 controls later steps of lymphatic vascular development and is responsible for establishing a collecting lymphatic vessel identity by regulating expression of downstream genes involved in lymphangiogenesis, including PDGF-beta, Delta-like 4 (Dll4) and angiopoietin (Ang)-2. Thus, FOXC2 is now recognized as a novel regulator of lymphatic vascular formation and remodeling. This review summarizes current knowledge about the function of FOXC2 in lymphangiogenesis and discusses prospects for future research in FOXC2-mediated pathological lymphangiogenesis in lymphatic-related disease.