The Pax6 isoform bearing an alternative spliced exon promotes the development of the neural retinal structure
The Pax6 isoform bearing an alternative spliced exon promotes the development of the neural retinal structure
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DOI：
10.1093/hmg/ddi069
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发表时间：
2005-03-15
影响因子：
3.5
通讯作者：
Nakafuku, M
中科院分区：
文献类型：
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作者：
Azuma, N;Tadokoro, K;Nakafuku, M
脊椎动物的视网膜上有一个视觉细胞紧密聚集的区域，这个区域被称为中央凹、中央区或视觉条纹。调控这些结构和视觉细胞梯度形成的分子机制尚不清楚。转录因子Pax6是眼睛发育的主要调控因子。Pax6（+5a）异构体与Pax6（-5a）异构体相比具有不同的DNA结合特性，该异构体在其配对结构域中包含一个5a编码的外显子插入14个氨基酸。对Pax6（+5a）的功能意义知之甚少。在这里，我们发现Pax6（+5a）特别在视网膜部分表达，在这里视觉细胞在眼睛发育过程中积累，当过表达时，诱导了一个显著的分化良好的视网膜样结构。在中央凹发育不全患者中发现的Pax6（+5a）蛋白发生点突变，不能诱导这些异位视网膜样结构。我们认为Pax6（+5a）在前眼中央凹、中央区或视觉条纹区诱导了一个发育级联，导致视网膜结构的形成，其中包含密集的视觉细胞。
The vertebrate retina has an area where visual cells are closely packed for proper vision that is known as a fovea, an area centralis or a visual streak. The molecular mechanism that regulates the formation of these structures and visual cell gradients is unknown. The transcription factor Pax6 is a master regulator of eye development. A Pax6 isoform that contains an exon 5a- encoded 14 amino acid insertion in its paired domain, Pax6(+5a), has different DNA- binding properties compared with the Pax6(-5a) isoform. Little is known about the functional significance of Pax6(+5a). Here, we show that Pax6(+5a) is expressed especially in the retinal portion where visual cells accumulate during eye development and, when overexpressed, induces a remarkable well- differentiated retina- like structure. Pax6(+5a) proteins that bear point mutations that are found in patients with foveal hypoplasia are unable to induce these ectopic retina- like structures. We propose that Pax6(+5a) induces a developmental cascade in the prospective fovea, area centralis or visual streak region that leads to the formation of a retinal architecture bearing densely packed visual cells.