Otx2 and Onecut1 promote the fates of cone photoreceptors and horizontal cells and repress rod photoreceptors.

Otx2 and Onecut1 promote the fates of cone photoreceptors and horizontal cells and repress rod photoreceptors.
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DOI:
10.1016/j.devcel.2013.06.005
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发表时间:
2013-07-15
期刊:
影响因子:
11.8
通讯作者:
Cepko, Constance L.
Cepko, Constance L.
中科院分区:
生物学1区
文献类型:
--
作者:
Emerson, Mark M.;Surzenko, Natalia;Goetz, Jillian J.;Trimarchi, Jeffrey;Cepko, Constance L.

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视锥细胞感光器在日光条件下进行光传导,并提供颜色视觉的关键第一步。尽管它们很重要,但人们对它们产生的发育机制知之甚少,特别是它们是如何相对于杆光感受器(在昏暗光线下启动视觉的细胞)确定的。在这里,我们报告的识别甲状腺激素受体β(Thrb)基因,早期锥标记的顺式调节模块(CRM)。我们发现,ThrbCRM 1是活跃的祖细胞偏向于生产锥和interneuronal细胞类型,水平细胞(HC)。ThrbCRM 1的分子分析表明,它是由Otx 2和Onecut 1转录因子的组合调控。Onecut1足以诱导具有最早的视锥细胞和毛细胞标志物的细胞。相反,干扰Onecut1的转录活性导致早熟杆的发展,这表明Onecut1是至关重要的定义锥与杆的命运。
Cone photoreceptors carry out phototransduction in daylight conditions and provide the critical first step in color vision. Despite their importance, little is known about the developmental mechanisms involved in their generation, particularly how they are determined relative to rod photoreceptors, the cells that initiate vision in dim light. Here, we report the identification of a cis-regulatory module (CRM) for the thyroid hormone receptor beta (Thrb) gene, an early cone marker. We found that ThrbCRM1 is active in progenitor cells biased to the production of cones and an interneuronal cell type, the horizontal cell (HC). Molecular analysis of ThrbCRM1 revealed that it is combinatorially regulated by the Otx2 and Onecut1 transcription factors. Onecut1 is sufficient to induce cells with the earliest markers of cones and HCs. Conversely, interference with Onecut1 transcriptional activity leads to precocious rod development, suggesting that Onecut1 is critically important in defining cone versus rod fates.
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