Expression of retinoid receptors during the retinoic acid-induced neuronal differentiation of human embryonal carcinoma cells

Retinoic acid (RA), a derivative of vitamin A, is essential for normal patterning and neurogenesis during development. Until recently, studies have been focused on the physiological roles of RA receptors (RARs), one of the two types of nuclear receptors, whereas the functions of the other nuclear receptors, retinoid X receptors (RXRs), have not been explored. Accumulating evidence now suggests that RXR alpha is a critical receptor component mediating the effects of RA during embryonic development. In this study, we have examined the expression profiles of RXR alpha and RARs during the RA-induced neuronal differentiation in a human embryonal carcinoma cell line, NT2. Distinct expression profiles of RXR alpha, RAR alpha, RAR beta, and RAR gamma were observed following treatment with RA. In particular, we found that RA treatment resulted in a biphasic up-regulation of RXR alpha expression in NT2 cells. The induced RXR alpha was found to bind specifically to the retinoid X response element based on gel mobility retardation assays. Furthermore, immunocytochemical analysis revealed that RXR alpha expression could be localized to the somatoaxonal regions of the NT2 neurons, including the tyrosine hydroxylase- and vasoactive intestinal peptide-positive neurons. Taken together, our findings provide the first demonstration of the cellular localization and regulation of RXR alpha expression in NT2 cells and suggest that RXR alpha might play a crucial role in the cellular functions of human CNS neurons.