Retinoic acid receptor-related orphan receptor α regulates a subset of cone genes during mouse retinal development
Retinoic acid receptor-related orphan receptor α regulates a subset of cone genes during mouse retinal development
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DOI：
10.1111/j.1471-4159.2008.05739.x
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发表时间：
2009-01-01
影响因子：
4.7
通讯作者：
Sasaki, Hiroshi
中科院分区：
文献类型：
--
作者：
Fujieda, Hiroki;Bremner, Rod;Sasaki, Hiroshi
色觉由视网膜锥光感受器支持，在大多数哺乳动物中，视网膜锥光感受器表达对短波长（S-视蛋白）或中波长（M-视蛋白）敏感的两种色素。分别编码S-视蛋白和M-视蛋白的Opn 1 sw和Opn 1 mw基因的表达受核受体的控制，包括甲状腺激素受体β 2（TR β 2）、类维生素A X受体γ（RXR γ）和ROR β（视黄酸受体相关孤儿受体（ROR）家族的成员）。我们现在证明，ROR α，ROR家族的另一个成员，调节Opn 1 sw，Opn 1 mw，以及Arr 3（锥抑制蛋白）在小鼠视网膜。出生后第3天在视锥细胞中检测到ROR α表达，并维持至成年。携带ROR α无效突变的staggerer小鼠的视网膜显示Opn 1 sw、Opn 1 mw和Arr 3的显著下调。ROR α与锥-杆同源框转录因子（Crx）协同作用，以在体外激活Opn 1 sw启动子。染色质免疫沉淀试验表明，ROR alpha在体内直接结合Opn 1 sw启动子、Opn 1 mw基因座控制区和Arr 3启动子。我们的数据表明，ROR α通过直接调节多个视锥基因在视锥发育中起着至关重要的作用。
Color vision is supported by retinal cone photoreceptors that, in most mammals, express two photopigments sensitive to short (S-opsin) or middle (M-opsin) wavelengths. Expression of the Opn1sw and Opn1mw genes, encoding S-opsin and M-opsin, respectively, is under the control of nuclear receptors, including thyroid hormone receptor beta 2 (TR beta 2), retinoid X receptor gamma (RXR gamma), and ROR beta, a member of the retinoic acid receptor-related orphan receptor (ROR) family. We now demonstrate that ROR alpha, another member of the ROR family, regulates Opn1sw, Opn1mw, as well as Arr3 (cone arrestin) in the mouse retina. ROR alpha expression is detected in cones by postnatal day 3 and maintained through adulthood. The retinas of staggerer mice, carrying a null mutation of ROR alpha, show significant down-regulation of Opn1sw, Opn1mw, and Arr3. ROR alpha acts in synergy with cone-rod homeobox transcription factor (Crx), to activate the Opn1sw promoter in vitro. Chromatin immunoprecipitation assays reveal that ROR alpha directly binds to the Opn1sw promoter, Opn1mw locus control region, and the Arr3 promoter in vivo. Our data suggest that ROR alpha plays a crucial role in cone development by directly regulating multiple cone genes.