Functional roles of Otx2 transcription factor in postnatal mouse retinal development
Functional roles of Otx2 transcription factor in postnatal mouse retinal development
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DOI：
10.1128/mcb.01209-07
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发表时间：
2007-12-01
影响因子：
5.3
通讯作者：
Furukawa, Takahisa
中科院分区：
文献类型：
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作者：
Koike, Chieko;Nishida, Akihiro;Furukawa, Takahisa
我们之前报道过 Otx2 对于感光细胞的命运决定至关重要；然而，尽管有报道Otx2在出生后阶段的视网膜双极细胞和光感受器中表达，但Otx2在出生后视网膜发育中的功能作用仍不清楚。在本研究中，我们首先通过分析Otx2来探讨Otx2在光感受器终末分化中的作用； Crx双敲除小鼠。在 Otx2(+/-) 中； Crx(-/-)视网膜中，光感受器变性和光感受器特异性基因的下调比Crx(-/-)视网膜中更为突出，表明Otx2在光感受器的终末分化中发挥作用。此外，双极细胞的Otx2(+/-)下降； Crx(-/-) 视网膜，表明 Otx2 也参与视网膜双极细胞的发育。为了进一步研究 Otx2 在双极细胞发育中的作用，我们构建了出生后双极细胞特异性 Otx2 条件敲除小鼠系。该细胞系的免疫组织化学分析表明，成熟双极细胞标志物蛋白激酶 C 的表达在视网膜中显着下调。视网膜电图显示，Otx2 消融导致视网膜双极细胞的电生理功能受损。这些数据表明 Otx2 在视网膜感光细胞和双极细胞的成熟中发挥功能性作用。
We previously reported that Otx2 is essential for photoreceptor cell fate determination; however, the functional role of Otx2 in postnatal retinal development is still unclear although it has been reported to be expressed in retinal bipolar cells and photoreceptors at postnatal stages. In this study, we first examined the roles of Otx2 in the terminal differentiation of photoreceptors by analyzing Otx2; Crx double-knockout mice. In Otx2(+/-); Crx(-/-) retinas, photoreceptor degeneration and downregulation of photoreceptor-specific genes were much more prominent than in Crx(-/-) retinas, suggesting that Otx2 has a role in the terminal differentiation of the photoreceptors. Moreover, bipolar cells decreased in the Otx2(+/-); Crx(-/-) retina, suggesting that Otx2 is also involved in retinal bipolar-cell development. To further investigate the role of Otx2 in bipolar-cell development, we generated a postnatal bipolar-cellspecific Otx2 conditional-knockout mouse line. Immunohistochemical analysis of this line showed that the expression of protein kinase C, a marker of mature bipolar cells, was significantly downregulated in the retina. Electroretinograms revealed that the electrophysiological function of retinal bipolar cells was impaired as a result of Otx2 ablation. These data suggest that Otx2 plays a functional role in the maturation of retinal photoreceptor and bipolar cells.