Analysis of transcriptional regulatory pathways of photoreceptor genes by expression profiling of the Otx2-deficient retina.
Analysis of transcriptional regulatory pathways of photoreceptor genes by expression profiling of the Otx2-deficient retina.
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DOI：
10.1371/journal.pone.0019685
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Furukawa T
中科院分区：
文献类型：
--
作者：
Omori Y;Katoh K;Sato S;Muranishi Y;Chaya T;Onishi A;Minami T;Fujikado T;Furukawa T
在脊椎动物视网膜中，Otx 2转录因子在视杆细胞和视锥细胞的细胞命运决定中起着至关重要的作用。我们以前报道过，Otx2条件性基因敲除（CKO）小鼠由于其细胞命运转化为无长突样细胞，因此在视网膜中完全不存在视杆细胞和视锥细胞。为了研究Otx2 CKO视网膜的整个转录组，我们使用微阵列比较了P1和P12时Otx2 CKO和野生型视网膜的表达谱。我们观察到101和1049探针组的表达在P1和P12时分别在Otx2 CKO视网膜中显著降低，而3和4149探针组的表达分别在P1和P12时增加。我们发现，在P1和P12的Otx2 CKO中，编码感光细胞发育相关转录因子的基因（包括Crx、Nrl、Nr2e3、Esrrb和NeuroD）的表达显著下调。此外，我们确定了三个人类视网膜疾病位点，这些位点与Otx2 CKO视网膜中某些下调基因（包括Ccdc126、Tnfsf13和Pitpnm1）非常接近，这表明这些基因可能与这些疾病有关。Otx2 CKO视网膜的这些转录组数据集提供了关于发育中的视杆细胞和视锥细胞的资源，以进一步了解感光细胞发育、功能和疾病的分子机制。
In the vertebrate retina, the Otx2 transcription factor plays a crucial role in the cell fate determination of both rod and cone photoreceptors. We previously reported that Otx2 conditional knockout (CKO) mice exhibited a total absence of rods and cones in the retina due to their cell fate conversion to amacrine-like cells. In order to investigate the entire transcriptome of the Otx2 CKO retina, we compared expression profile of Otx2 CKO and wild-type retinas at P1 and P12 using microarray. We observed that expression of 101- and 1049-probe sets significantly decreased in the Otx2 CKO retina at P1 and P12, respectively, whereas, expression of 3- and 4149-probe sets increased at P1 and P12, respectively. We found that expression of genes encoding transcription factors involved in photoreceptor development, including Crx, Nrl, Nr2e3, Esrrb, and NeuroD, was markedly down-regulated in the Otx2 CKO at both P1 and P12. Furthermore, we identified three human retinal disease loci mapped in close proximity to certain down-regulated genes in the Otx2 CKO retina including Ccdc126, Tnfsf13 and Pitpnm1, suggesting that these genes are possibly responsible for these diseases. These transcriptome data sets of the Otx2 CKO retina provide a resource on developing rods and cones to further understand the molecular mechanisms underlying photoreceptor development, function and disease.
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DOI：
10.1073/pnas.0902425106
发表时间：
2009-10-13
影响因子：
11.1
作者：
Jia, Li;Oh, Edwin C. T.;Forrest, Douglas
通讯作者：
Forrest, Douglas
在增强型 S 锥体综合征小鼠模型中表达视杆细胞和视锥细胞基因的混合光感受器。
影响因子：
4.5
作者：
Corbo, JC;Cepko, CL
通讯作者：
Cepko, CL
影响因子：
2.5
作者：
de Melo, J;Qiu, XG;Eisenstat, DD
通讯作者：
Eisenstat, DD
影响因子：
64.5
作者：
Furukawa, T;Morrow, EM;Cepko, CL
通讯作者：
Cepko, CL
影响因子：
64.5
作者：
Gerdes JM;Davis EE;Katsanis N
通讯作者：
Katsanis N