Retinoid X receptor γ is necessary to establish the S-opsin gradient in cone photoreceptors of the developing mouse retina
Retinoid X receptor γ is necessary to establish the S-opsin gradient in cone photoreceptors of the developing mouse retina
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DOI：
10.1167/iovs.05-0093
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发表时间：
2005-08-01
影响因子：
4.4
通讯作者：
Reh, TA
中科院分区：
文献类型：
--
作者：
Roberts, MR;Hendrickson, A;Reh, TA
目的。类视黄醇X受体（RXRs）是配体依赖性核激素受体家族的成员。其中一种基因RXR γ在发育中的中枢神经系统（CNS）的高度受限区域表达，包括视网膜。尽管先前的研究已经将RXR γ定位于几种物种中发育中的视锥感受器，但其在这些细胞中的功能尚不清楚。先前的研究表明，甲状腺激素受体β 2 （TR β 2）通过激活中波长(M)视锥蛋白和抑制短波长(S)视锥蛋白来建立小鼠正常的视锥模式。甲状腺激素受体常以异源二聚体形式通过rxrs调节基因转录。为了确定RXR γ是否与TR β 2协同调节视锥蛋白的模式，我们检测了RXR γ的发育表达，并分析了RXR γ缺失小鼠视锥蛋白的表达。RXR γ在有丝分裂后视锥细胞中表达，并在S-opsin开始时在小鼠和人视锥细胞中短暂下调。RXR γ -缺失小鼠在所有视锥细胞中表达s -视蛋白，与TR β 2缺失小鼠相似。与TR β 2缺失小鼠不表达M-opsin不同，RXR γ缺失小鼠的M-opsin表达模式正常。RXR γ对抑制所有未成熟视锥细胞和成熟视网膜背视锥细胞中的s -视蛋白是必需的（与TR β 2一起），但对m -视蛋白的调节不是必需的。这些结果表明RXRs在调节中枢神经系统细胞分化中起着关键作用，并突出了从果蝇到哺乳动物的视蛋白调节的显著保守性。
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 beta 2 (TR beta 2) 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 TR beta 2 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 TR beta 2-null mice. Unlike TR beta 2-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 TR beta 2) 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.