Rax Homeoprotein Regulates Photoreceptor Cell Maturation and Survival in Association with Crx in the Postnatal Mouse Retina
Rax Homeoprotein Regulates Photoreceptor Cell Maturation and Survival in Association with Crx in the Postnatal Mouse Retina
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DOI：
10.1128/mcb.00048-15
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发表时间：
2015-08-01
影响因子：
5.3
通讯作者：
Furukawaa, Takahisa
中科院分区：
文献类型：
--
作者：
Irie, Shoichi;Sanuki, Rikako;Furukawaa, Takahisa
Rax同源框基因在脊椎动物视网膜发育的多个过程中起着重要作用。许多脊椎动物物种拥有Rax和Rax 2基因，并且已经提出了不同的功能。相比之下，小鼠含有单个Rax基因，其在视网膜发育后期的功能作用仍不清楚。为了阐明小鼠Rax在出生后光感受器发育和维持中的功能，我们产生了条件性敲除小鼠，其中成熟或成熟光感受器细胞中的Rax通过他莫昔芬治疗而失活（Rax iCKO小鼠）。当Rax在出生后Rax iCKO小鼠中失活时，发育中的感光细胞显示出视杆和视锥感光细胞基因表达水平的显著降低，并且成熟的成年感光细胞表现出视锥细胞数量的特定减少。在荧光素酶测定中，我们发现Rax和Crx协同反式激活视紫红质和视锥蛋白启动子，并且存在反式激活感光基因表达的最佳Rax表达水平。此外，Rax和Crx共定位于成熟的感光细胞，并在培养的细胞中观察到它们的共免疫沉淀。两者合计，这些结果表明，Rax起着至关重要的作用，在视锥细胞和视杆细胞的成熟和视锥细胞的生存，通过调节感光基因表达与Crx在出生后的小鼠视网膜。
The Rax homeobox gene plays essential roles in multiple processes of vertebrate retina development. Many vertebrate species possess Rax and Rax2 genes, and different functions have been suggested. In contrast, mice contain a single Rax gene, and its functional roles in late retinal development are still unclear. To clarify mouse Rax function in postnatal photoreceptor development and maintenance, we generated conditional knockout mice in which Rax in maturing or mature photoreceptor cells was inactivated by tamoxifen treatment (Rax iCKO mice). When Rax was inactivated in postnatal Rax iCKO mice, developing photoreceptor cells showed a significant decrease in the level of the expression of rod and cone photoreceptor genes and mature adult photoreceptors exhibited a specific decrease in cone cell numbers. In luciferase assays, we found that Rax and Crx cooperatively transactivate Rhodopsin and cone opsin promoters and that an optimum Rax expression level to transactivate photoreceptor gene expression exists. Furthermore, Rax and Crx colocalized in maturing photoreceptor cells, and their coimmunoprecipitation was observed in cultured cells. Taken together, these results suggest that Rax plays essential roles in the maturation of both cones and rods and in the survival of cones by regulating photoreceptor gene expression with Crx in the postnatal mouse retina.