Cone opsin patterning in the mouse retina is controlled by thyroid hormone receptor ß2

Abstract

Abstract: : Purpose: Deletion of thyroid hormone receptor (TR) ß2 perturbs mouse cone opsin spatial patterning by derepressing S opsin dorsally and completely abolishing M opsin expression. We sought to map the expression of TRs in the mouse retina and to determine the molecular mechanism by which TRs regulate cone opsin expression. Methods:RT–PCR and in situ hybridization were used to monitor the spatiotemporal expression of TR isoforms α, ß1, and ß2 in wildtype (WT) mouse retinas from embryonic day 15 to postnatal day 60. Cone opsin distribution was evaluated with opsin specific antibodies in WT, TRß2^–/–, TRß^GS/GS (incapable of DNA–binding), and TRß^Δ337T (incapable of ligand–T3–binding) mice. Results: In the WT mouse retina, TRα, ß1, and ß2 are differentially expressed throughout all developmental stages examined. TRß1 and TRß2 are localized exclusively to cone photoreceptors. Their mRNA levels diminish from the dorsal to ventral retina. TRß2^–/–, TRß^GS/GS and TRß^Δ337T mice show no expression of M opsin throughout their retina. In these transgenics, S opsin is fully expressed in the dorsal retina in contrast to a gradient of expression in the WT mouse. Conclusions:The spatiotemporal characteristics of TRß2 expression are consistent with the control of dorsoventral gradients in S opsin expression. TRß2 at higher levels functions, directly or indirectly, as a repressor of S opsin. TRß2 serves as an activator of M opsin. The knock–out and knock–in models indicate that the function of TRß2 as a repressor for S opsin or activator of M opsin expression depends on both DNA and ligand binding.

Keywords: opsins • transcription factors • retinal development