FOXC2 TRANSCRIPTION FACTOR: A NOVEL REGULATOR OF LYMPHANGIOGENESIS

Abstract

Lymphangiogenesis is the critical processof forming new lymphatic vessels underphysiological and pathological conditions andinvolves both molecular and morphologicalchanges. Despite evidence that lymphangiogenicfactors, including vascular endothelialgrowth factors (VEGFs) and Prox1, regulatelymphangiogenesis, the molecular mechanismsunderlying gene regulation in lymphatic vesselremodeling and maturation are not fullyunderstood. Importantly, recent studiesdemonstrate that Forkhead transcriptionfactor FOXC2 controls later steps of lymphaticvascular development and is responsible forestablishing a collecting lymphatic vesselidentity by regulating expression of downstreamgenes involved in lymphangiogenesis,including PDGF-ß, Delta-like 4 (Dll4) andangiopoietin (Ang)-2. Thus, FOXC2 is nowrecognized as a novel regulator of lymphaticvascular formation and remodeling. Thisreview summarizes current knowledge aboutthe function of FOXC2 in lymphangiogenesisand discusses prospects for future research inFOXC2-mediated pathological lymphangiogenesisin lymphatic-related disease.