Functional specificity of the two retinoic acid receptor RAR and RXR families in myogenesis

Abstract

In C2 myoblasts, retinoic acid (RA) is an efficient inducer of both growth arrest and differentiation. These RA effects are mediated through at least two classes of retinoic acid receptors (RARs and RXRs), which belong to the nuclear receptor superfamily. To determine the role played by each RAR or RXR family in this model system, we have analysed the effects of RA in C2 myoblasts expressing a dominant negative RAR (dnRAR) or a dominant negative RXR (dnRXR). The stable expression of dnRAR or dnRXR in C2 cells delays the RA-induced growth arrest and differentiation, an effect which is more pronounced in C2-dnRXR myoblasts. Furthermore, the RA-inducible expression of MyoD gene is lost in C2-dnRXR but not in C2-dnRAR cells, indicating that each family of retinoid receptors RAR and RXR may regulate distinct subsets of RA-responsive genes. Finally, using C2 cell lines with different retinoid responsiveness, we provided evidence for a link between the RXR and MyoD families in the process of myogenic differentiation. These results illustrate a critical role for RA-receptors in RA-control of C2 myogenesis and provide tools for studying the function of RA and its receptors during vertebrate development.