Center for Molecular and Human Genetics, The Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA.
Dev Biol. 2010 Mar 15;339(2):494-506. doi: 10.1016/j.ydbio.2009.12.032. Epub 2010 Jan 7.
The retinal homeobox (Rx) gene product is essential for eye development. However little is known about its molecular function. It has been demonstrated that Rx binds to photoreceptor conserved element (PCE-1), a highly conserved element found in the promoter region of photoreceptor-specific genes such as rhodopsin and red cone opsin. We verify that Rx is co-expressed with rhodopsin and red cone opsin in maturing photoreceptors and demonstrate that Rx binds to the rhodopsin and red cone opsin promoters in vivo. We also find that Rx can cooperate with the Xenopus analogs of Crx and Nrl, otx5b and XLMaf (respectively), to activate a Xenopus opsin promoter-dependent reporter. Finally, we demonstrate that reduction of Rx expression in tadpoles results in decreases in expression of several PCE-1 containing photoreceptor genes, abnormal photoreceptor morphology, and impaired vision. Our data suggests that Rx, in combination with other transcription factors, is necessary for normal photoreceptor gene expression, maintenance, and function. This establishes a direct role for Rx in regulation of genes expressed in a differentiated cell type.
视网膜同源盒（Rx）基因产物对眼睛发育至关重要。然而，人们对其分子功能知之甚少。已经证明 Rx 与光感受器保守元件（PCE-1）结合，PCE-1 是一种高度保守的元件，存在于视紫红质和红锥光感受蛋白等光感受器特异性基因的启动子区域中。我们验证了 Rx 在成熟的光感受器中与视紫红质和红锥光感受蛋白共同表达，并证明 Rx 在体内与视紫红质和红锥光感受蛋白启动子结合。我们还发现，Rx 可以与 Xenopus 的 Crx 和 Nrl、otx5b 和 XLMaf（分别）的类似物相互作用，激活依赖 Xenopus 视蛋白启动子的报告基因。最后，我们证明在蝌蚪中降低 Rx 的表达会导致几种包含 PCE-1 的光感受器基因表达减少、光感受器形态异常和视力受损。我们的数据表明，Rx 与其他转录因子一起，是正常光感受器基因表达、维持和功能所必需的。这确立了 Rx 在调节分化细胞类型中表达的基因中的直接作用。
