The spatial patterning of mouse cone opsin expression is regulated by bone morphogenetic protein signaling through downstream effector COUP-TF nuclear receptors.
The spatial patterning of mouse cone opsin expression is regulated by bone morphogenetic protein signaling through downstream effector COUP-TF nuclear receptors.
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DOI：
10.1523/jneurosci.0951-09.2009
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发表时间：
2009-10-07
期刊：
影响因子：
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通讯作者：
Watanabe S
中科院分区：
文献类型：
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作者：
Satoh S;Tang K;Iida A;Inoue M;Kodama T;Tsai SY;Tsai MJ;Furuta Y;Watanabe S
视锥光色素，被称为视蛋白，是关键元素，也是色觉中使用的第一个检测模块。在小鼠中，视锥体光感受器分布于整个视网膜，S-视蛋白和m -视蛋白在视网膜中具有独特的表达模式，沿背腹侧轴呈梯度；然而，调节视锥蛋白表达的空间模式的机制尚未得到很好的记录。本研究的目的是确定调节视锥蛋白表达的空间模式的机制。通过分析骨形态发生蛋白（BMP）信号的敲除，我们发现BMP在形成视网膜视锥蛋白表达模式中起重要作用；然而，在视网膜发育早期，BMP信号仅在视网膜背侧短暂激活。因此，BMP不太可能在视蛋白基因表达中起直接作用，视蛋白基因表达始于视网膜发育的后期阶段。我们发现鸡卵白蛋白上游启动子转录因子（COUP-TF）核受体是BMP和视蛋白表达之间的联系。BMP信号对于COUP-TFI和-TFII的正确背腹空间表达至关重要。通过功能增益和功能损失分析，我们发现COUP-TFI和- tfii都需要抑制背侧视网膜中s-视蛋白的表达，但只有COUP-TFI在抑制腹侧视网膜中m -视蛋白的表达中起重要作用。基于这些发现，我们提出了一个涉及BMP和coup - tf的新的分子级联，该级联传递背腹侧信息，以指导视网膜发育过程中视锥蛋白的表达。
Cone photopigments, known as opsins, are pivotal elements and the first detection module employed in color vision. In mice, cone photoreceptors are distributed throughout the retina, and S- and M-opsins have unique expression patterns in the retina with a gradient along the dorsoventral axis; however, the mechanisms regulating the spatial patterning of cone opsin expression have not been well documented. The purpose of this study was to define the mechanisms regulating the spatial patterning of cone opsin expression. By analyzing knockouts for bone morphogenetic protein (BMP) signaling, we found an essential role for BMP in forming cone opsin expression patterns in the retina; however, BMP signaling is activated only transiently in the dorsal half of the retina during early retinal development. Thus, BMP is not likely to play a direct role in opsin gene expression, which starts at a later stage of retinal development. We identified the chicken ovalbumin upstream promoter-transcription factor (COUP-TF) nuclear receptor as a link between BMP and opsin expression. BMP signaling is essential for the correct dorsoventral spatial expression of COUP-TFI and -TFII. Through gain- and loss-of-function analyses, we found that both COUP-TFI and -TFII are required to suppress S-opsin expression in the dorsal retina but that only COUP-TFI plays an essential role in suppressing M-opsin expression in the ventral retina. Based on these findings, we propose a new molecular cascade involving BMP and COUP-TFs that conveys dorsoventral information to direct the expression of cone opsins during retinal development.