The chicken RaxL gene plays a role in the initiation of photoreceptor differentiation
The chicken RaxL gene plays a role in the initiation of photoreceptor differentiation
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DOI：
10.1242/dev.00114
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发表时间：
2002-12-01
期刊：
影响因子：
4.6
通讯作者：
Cepko, CL
中科院分区：
文献类型：
--
作者：
Chen, CMA;Cepko, CL
配对型同源结构域基因Rax先前被确定为小鼠和人类早期眼睛形成的关键分子。本文报道了鸡Rax家族成员Rax和RaxL的表达模式，以及RaxL在光感受器发育中的作用。Rax和RaxL均在早期视网膜祖细胞中表达，其中Rax的表达水平明显高于RaxL。在光感受器开始形成的时候，RaxL在增殖祖细胞区域内的一个细胞亚群中以相对较高的水平出现。随后，它在迁移到感光层的细胞中表达，在感光层分化的初始阶段，而不是后期阶段，它高度表达。为了测试RaxL的功能，利用逆转录病毒载体在体内将RaxL的一个推定的显性负等位基因（EnRaxLDeltaC）引入早期鸡眼。EnRaxLDeltaC，而不是显性阴性Rax (EnRaxDeltaC)，导致光感受器细胞早期标记物的表达显著降低。对RaxL在具有典型光感受器特异性增强子元件的报告结构体上的交易激活活性的检测表明，RaxL表现出显著的激活活性，并且这种活性在EnRaxLDeltaC的存在下严重降低。对体内光感受器基因表达的影响是特异性的，因为其他细胞类型不受影响，视网膜中的一般增殖也是如此。表达光感受器标记的细胞数量减少可能是由于发育中的光感受器细胞存活率降低，因为在表达显性阴性RaxL的视网膜细胞中凋亡增加。我们提出RaxL在鸡视网膜感光细胞分化的起始和可能的承诺中起作用。
The paired type homeodomain gene, Rax, was previously identified as a key molecule in early eye formation in mice and humans. We report the expression patterns of two Rax family members from chicken, Rax and RaxL, and on the function of RaxL in photoreceptor development. Both Rax and RaxL are expressed in early retinal progenitor cells, with Rax being expressed at a significantly higher level than RaxL. At the time that photoreceptors begin to form, RaxL appears at a relatively high level in a subset of cells within the zone of proliferating progenitor cells. Subsequently, it is expressed in cells migrating to the photoreceptor layer, where it is highly expressed during the initial, but not late, stages of photoreceptor differentiation. To test the function of RaxL, a putative dominant-negative allele of RaxL comprising a fusion of the engrailed repressor domain and a region of RaxL (EnRaxLDeltaC) was introduced in vivo into the early chick eye using a retroviral vector. EnRaxLDeltaC, but not the dominant negative Rax (EnRaxDeltaC), caused a significant reduction in expression of early markers of photoreceptor cells. Examination of the transactivation activity of RaxL on a reporter construct bearing a canonical photoreceptor-specific enhancer element showed that RaxL exhibited significant activation activity, and that this activity was severely diminished in the presence of EnRaxLDeltaC. The effect on photoreceptor gene expression in vivo was specific in that other cell types were unaffected, as was general proliferation in the retina. The reduction in numbers of cells expressing photoreceptor markers was probably due to decreased survival of developing photoreceptor cells, as there was increased apoptosis among cells of the retina expressing dominant-negative RaxL. We propose that RaxL plays a role in the initiation of differentiation, and also possibly commitment, of photoreceptor cells in the chicken retina.