Goetz Jillian J, Martin Gregory M, Chowdhury Rebecca, Trimarchi Jeffrey M
Department of Genetics, Development and Cell Biology, Iowa State University, Ames, Iowa, United States of America.
PLoS One. 2014 Oct 14;9(10):e110194. doi: 10.1371/journal.pone.0110194. eCollection 2014.
The entire repertoire of intrinsic factors that control the cell fate determination process of specific retinal neurons has yet to be fully identified. Single cell transcriptome profiling experiments of retinal progenitor cells revealed considerable gene expression heterogeneity between individual cells, especially among different classes of transcription factors. In this study, we show that two of those factors, Onecut1 and Onecut2, are expressed during mouse retinal development. Using mice that are deficient for each of these transcription factors, we further demonstrate a significant loss (∼70-80%) of horizontal cells in the absence of either of these proteins, while the other retinal cells appear at normal numbers. Microarray profiling experiments performed on knockout retinas revealed defects in horizontal cell genes as early as E14.5. Additional profiling assays showed an upregulation of several stress response genes in the adult Onecut2 knockout, suggesting that the integrity of the retina is compromised in the absence of normal numbers of horizontal cells. Interestingly, melanopsin, the gene coding for the photopigment found in photosensitive ganglion cells, was observed to be upregulated in Onecut1 deficient retinas, pointing to a possible regulatory role for Onecut1. Taken together, our data show that similar to Onecut1, Onecut2 is also necessary for the formation of normal numbers of horizontal cells in the developing retina.
控制特定视网膜神经元细胞命运决定过程的所有内在因素尚未完全确定。视网膜祖细胞的单细胞转录组分析实验表明，单个细胞之间存在相当大的基因表达异质性，尤其是在不同类别的转录因子之间。在本研究中，我们表明其中两个因子Onecut1和Onecut2在小鼠视网膜发育过程中表达。利用缺乏这些转录因子的小鼠，我们进一步证明，在缺乏这两种蛋白质中的任何一种时，水平细胞会显著减少（约70-80%），而其他视网膜细胞数量正常。对基因敲除视网膜进行的微阵列分析实验早在E14.5时就发现了水平细胞基因的缺陷。额外的分析检测显示，成年Onecut2基因敲除小鼠中有几个应激反应基因上调，这表明在水平细胞数量不正常的情况下，视网膜的完整性受到了损害。有趣的是，在Onecut1基因敲除的视网膜中，观察到编码感光神经节细胞中光色素的基因黑素视蛋白上调，这表明Onecut1可能具有调节作用。综上所述，我们的数据表明，与Onecut1一样，Onecut2对于发育中的视网膜中正常数量水平细胞的形成也是必需的。
