Neural crest stem cells (NCSC) can differentiate to neurons, glia, melanocytes and smooth muscle cells under stimulation with different growth factors.Transforming growth factor-beta (TGF-β) converts NCSC to smooth muscle cell (SMC) phenotype.By using a NCSC line, we developed and characterized an in vitro model system to study NCSC differentiation to SMC.We found that TGF-β not only induced biochemical and morphological alteration of NCSC, but also converted the NCSC to a functional SMC, i.e.contractile phenotype.Additional studies revealed that Smad and RhoA signaling pathways played a critical role in TGF-β-mediated NCSC differentiation.