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(Investigative Ophthalmology and Visual Science. 2005;46:2897-2904.)
© 2005 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.05-0093
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Retinoid X Receptor {gamma} Is Necessary to Establish the S-opsin Gradient in Cone Photoreceptors of the Developing Mouse Retina

Melanie R. Roberts,1,2 Anita Hendrickson,2 Christopher R. McGuire,2 and Thomas A. Reh2

1From the Graduate Program in Neurobiology and Behavior and the 2Department of Biological Structure, University of Washington, Seattle, Washington.

PURPOSE. The retinoid X receptors (RXRs) are members of the family of ligand-dependent nuclear hormone receptors. One of these genes, RXR{gamma}, is expressed in highly restricted regions of the developing central nervous system (CNS), including the retina. Although previous studies have localized RXR{gamma} to developing cone photoreceptors in several species, its function in these cells is unknown. A prior study showed that thyroid hormone receptor ß2 (TRß2) 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 RXR{gamma} cooperates with TRß2 to regulate cone opsin patterning, the developmental expression of RXR{gamma} was examined, and cone opsin expression in RXR{gamma}-null mice was analyzed.

RESULTS. RXR{gamma} was expressed in postmitotic cones and was transiently downregulated at the time of S-opsin onset in both mouse and human cones. RXR{gamma}-null mice expressed S-opsin in all cones, similar to the TRß2-null mice. Unlike TRß2-null mice, which did not express M-opsin, RXR{gamma}-null mice had a normal pattern of M-opsin expression.

CONCLUSIONS. RXR{gamma} is essential (along with TRß2) 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.




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