The SOX genes comprise a family of transcriptional regulators implicated in the control of nervous system development. The developing brain is the major site of expression of many Sox genes. Sox2 and Sox3 genes are predominantly expressed in the immature, undifferentiated cells of the neural epithelium throughout the entire CNS. NTERA2 is a human embryonal carcinoma cell line that phenotypically represents undifferentiated, pluripotent embryonic stem cells. In the presence of retinoic acid, cells differentiate into mature neurons providing an in vitro model for studying human genes that promote and regulate neural differentiation. In this study it is shown for the first time that the retinoic acid-induced neuronal differentiation of NTERA2 cells is accompanied by down-regulation of SOX2 and up-regulation of SOX3 gene during early phases of induction. These data suggest that the effects of retinoic acid on neural differentiation of NTERA2 EC cells might be mediated by modulation of SOX2 and SOX3 gene expression.