Regulatory interactions of signaling pathways and transcription factors in heart valve development. Signaling pathways including Notch, Transforming growth factor (TGF), Bone morphogenetic protein (BMP), and Wnt, with transcription factors including Twist1, Tbx20 and Msx1/2 are involved in endocardial cushion (EC) formation during early valvulogenesis. NFATc1 signaling contributes to elongation and remodeling of the EC. During valve maturation, BMP signaling induces cartilage-associated genes Sox9 and aggrecan. Fibroblast growth factor (FGF) signaling promotes expression of scleraxis and tenascin, which are characteristic of tendon cell lineages. These genes and pathways involved in valve development also are active in adult valve disease.