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

Retinoic acid (RA), a derivative of vitamin A, is essential for normal patt erning and neurogenesis during development. Until recently, studies have be en focused on the physiological roles of RA receptors (RARs), one of the tw o types of nuclear receptors, whereas the functions of the other nuclear re ceptors, retinoid X receptors (RXRs), have not been explored. Accumulating evidence now suggests that RXR alpha is a critical receptor component media ting the effects of RA during embryonic development. In this study, we have examined the expression profiles of RXR alpha and RARs during the RA-induc ed neuronal differentiation in a human embryonal carcinoma cell line, NT2. Distinct expression profiles of RXR alpha, RAR alpha, RAR beta, and RAR gam ma were observed following treatment with RA. In particular, we found that RA treatment resulted in a biphasic up-regulation of RXR alpha expression i n NT2 cells. The induced RXR alpha was found to bind specifically to the re tinoid X response element based on gel mobility retardation assays. Further more, 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. T aken together, our findings provide the first demonstration of the cellular localization and regulation of RXR alpha expression in NT2 cells and sugge st that RXR alpha might play a crucial role in the cellular functions of hu man CNS neurons.