PURPOSE: The retinoid X receptors (RXRs) are members of the family of ligand-dependent nuclear hormone receptors. One of these genes, RXRgamma, is expressed in highly restricted regions of the developing central nervous system (CNS), including the retina. Although previous studies have localized RXRgamma to developing cone photoreceptors in several species, its function in these cells is unknown. A prior study showed that thyroid hormone receptor beta2 (TRbeta2) is necessary to establish proper cone patterning in mice by activating medium-wavelength (M) cone opsin and suppressing short-wavelength (S) cone opsin. Thyroid hormone receptors often regulate gene transcription as heterodimeric complexes with RXRs. METHODS: To determine whether RXRgamma cooperates with TRbeta2 to regulate cone opsin patterning, the developmental expression of RXRgamma was examined, and cone opsin expression in RXRgamma-null mice was analyzed. RESULTS: RXRgamma was expressed in postmitotic cones and was transiently downregulated at the time of S-opsin onset in both mouse and human cones. RXRgamma-null mice expressed S-opsin in all cones, similar to the TRbeta2-null mice. Unlike TRbeta2-null mice, which did not express M-opsin, RXRgamma-null mice had a normal pattern of M-opsin expression. CONCLUSIONS: RXRgamma is essential (along with TRbeta2) for suppressing S-opsin in all immature cones and in dorsal cones in the mature retina, but it is not necessary for M-opsin regulation. These results demonstrate a critical role for RXRs in regulating cell differentiation in the CNS and highlight a remarkable conservation of opsin regulation from Drosophila to mammals.
PURPOSE: The retinoid X receptors (RXRs) are members of the family of ligand-dependent nuclear hormone receptors. One of these genes, RXRgamma, is expressed in highly restricted regions of the developing central nervous system (CNS), including the retina. Although previous studies have localized RXRgamma to developing cone photoreceptors in several species, its function in these cells is unknown. A prior study showed that thyroid hormone receptor beta2 (TRbeta2) is necessary to establish proper cone patterning in mice by activating medium-wavelength (M) cone opsin and suppressing short-wavelength (S) cone opsin. Thyroid hormone receptors often regulate gene transcription as heterodimeric complexes with RXRs. METHODS: To determine whether RXRgamma cooperates with TRbeta2 to regulate cone opsin patterning, the developmental expression of RXRgamma was examined, and cone opsin expression in RXRgamma-null mice was analyzed. RESULTS: RXRgamma was expressed in postmitotic cones and was transiently downregulated at the time of S-opsin onset in both mouse and human cones. RXRgamma-null mice expressed S-opsin in all cones, similar to the TRbeta2-null mice. Unlike TRbeta2-null mice, which did not express M-opsin, RXRgamma-null mice had a normal pattern of M-opsin expression. CONCLUSIONS: RXRgamma is essential (along with TRbeta2) for suppressing S-opsin in all immature cones and in dorsal cones in the mature retina, but it is not necessary for M-opsin regulation. These results demonstrate a critical role for RXRs in regulating cell differentiation in the CNS and highlight a remarkable conservation of opsin regulation from Drosophila to mammals.
Authors: Melanie R Roberts; Maya Srinivas; Douglas Forrest; Gabriella Morreale de Escobar; Thomas A Reh Journal: Proc Natl Acad Sci U S A Date: 2006-04-10 Impact factor: 11.205