COUP-TFI and -TFII nuclear receptors are expressed in amacrine cells and play roles in regulating the differentiation of retinal progenitor cells

COUP-TFI and -TFII nuclear receptors are expressed in amacrine cells and play roles in regulating the differentiation of retinal progenitor cells
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DOI:
10.1016/j.exer.2009.09.009
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发表时间:
2010-01-01
影响因子:
3.4
通讯作者:
Watanabe, Sumiko
Watanabe, Sumiko
中科院分区:
医学3区
文献类型:
--
作者:
Inoue, Mariko;Iida, Atsumi;Watanabe, Sumiko

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鸡卵清蛋白上游启动子转录因子是类固醇/甲状腺激素受体超家族的成员。我们已经证明了两个同源的COUP-TF基因,COUP-TFI和COUP-TFII,在发育中的小鼠视网膜中以独特的沿背腹轴的梯度表达。在这项工作中,我们旨在描述COUP-TF在成熟视网膜中的详细表达模式。此外,还检测了它们在视网膜前体细胞分化为成熟视网膜细胞亚型中的作用。对冰冻的小鼠视网膜切片进行免疫组织化学染色,发现Coup-TFI和-TFII在无长突细胞中表达,尤其是在成熟小鼠视网膜的甘氨酸能亚型中。逆转录病毒介导的基因转移强制表达COUP-TFI和-TFII促进无长突和视锥感光细胞分化,而视杆感光细胞分化减少。COUP-TFI和-TFII表达水平的变化不影响细胞的增殖和凋亡。在Y79视网膜母细胞瘤细胞系中,我们观察到COUP-TFI和-TFII抑制了NRL基因的转录激活。然后我们分析了与COUP-TFI和-TFII结构相对较远的COUP-Tf转录因子的另一个成员-COUP-TFγ。当Coup-Tf-γ异位表达于视网膜外植体时,它主要在水平细胞中表达,诱导无长突细胞的活性较弱。综上所述,我们发现COUP-TFI和-TFII在无长突细胞分化中起作用,并且COUP-TFγ在视网膜发育过程中有不同的表达模式和作用。(C)2009爱思唯尔有限公司。保留所有权利。
Chicken ovalbumin upstream promoter transcription factors (CCUP-TFs) are members of the steroid/thyroid hormone receptor superfamily. We have shown that two homologous COUP-TF genes, COUP-TFI and COUP-TFII, are expressed in developing mouse retina with a unique gradient along the dorsal-ventral axis. In this work, we aimed to characterize the detailed expression patterns of COUP-TFs in mature retina. Their functions in retinal progenitor cell differentiation into subtypes of mature retinal cells were also examined. Immunostaining of frozen mouse retinal sections with antibodies against CCUP-TFs and markers for retinal subtypes revealed that COUP-TFI and -TFII are expressed in amacrine cells, especially in a glycinergic subtype in mature mouse retina. Forced expression of COUP-TFI and -TFII in mouse retinal explant culture by retrovirus-mediated gene transfer promoted amacrine and cone photoreceptor cell differentiation, whereas that of rod photoreceptors decreased. Cell proliferation and apoptosis were not affected by the perturbation of COUP-TFI and -TFII expression levels. Using the Y79 retinoblastoma cell line, we observed that COUP-TFI and -TFII suppressed the transcriptional activation of the Nrl gene. We then analyzed one another member of COUP-TF transcription factors, COUP-TF gamma, whose structure is relatively distant from those of COUP-TFI and -TFII. It is expressed mainly in horizontal cells and has weak activity in inducing amacrine cells when COUP-TF gamma was ectopically expressed in retinal explants. In summary, we found that COUP-TFI and -TFII play roles in amacrine cell differentiation, and COUP-TF gamma has distinct: expression pattern and roles during retinal development. (C) 2009 Elsevier Ltd. All rights reserved.