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Selective induction of retinal photoreceptors out of iris pigment epithelial cells.

从虹膜色素上皮细胞选择性诱导视网膜感光器。

基本信息

批准号：
18591946
负责人：
AKIHIRO Nishida
金额：
$ 2.57万
依托单位：
Osaka Bioscience Institute
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591946/
关键词：
Retinal hotoreceptor Crx Otx2 retinal bipolar knockout mouse L7 cell differentiation homeobox

项目摘要

We previously reported that Otx2 is essential for photoreceptor cell fate determination (Nishida, et. al., Nat. Neurosci., 6, 1255-1263, 2003), 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-cell-specific 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. We reported these results in Molecular and Cellular Biology (27 p 8318-8329, 2007).

我们先前报道了Otx 2对于光感受器细胞命运决定是必需的（Nishida，et.例如，Nat. Neurosci.，6，1255-1263，2003），然而，尽管已报道Otx 2在出生后阶段在视网膜双极细胞和光感受器中表达，但其在出生后视网膜发育中的功能作用仍不清楚。在这项研究中，我们首先检查的作用，Otx 2光感受器的终末分化分析Otx 2; Crx双敲除小鼠。在Otx 2 ^<+/->; 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^<-/->视网膜中显著得多，表明Otx 2在光感受器的终末分化中具有作用。此外，Otx 2 ^<+/->; Crx^<-/->视网膜中的双极细胞减少，表明Otx 2也参与视网膜双极细胞的发育。为了进一步研究Otx 2在双极细胞发育中的作用，我们产生了出生后双极细胞特异性Otx 2条件性敲除小鼠系。免疫组化分析表明，蛋白激酶C的表达，成熟的双极细胞的标志物，在视网膜中显着下调。视网膜电图显示，由于Otx 2消融，视网膜双极细胞的电生理功能受损。这些数据表明，Otx 2在视网膜感光细胞和双极细胞的成熟中起着功能性作用。我们在《分子和细胞生物学》（27 p 8318-8329，2007）中报道了这些结果。