The early retinal progenitor-expressed gene Sox11 regulates the timing of the differentiation of retinal cells
The early retinal progenitor-expressed gene Sox11 regulates the timing of the differentiation of retinal cells
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DOI：
10.1242/dev.090274
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发表时间：
2013-02-15
期刊：
影响因子：
4.6
通讯作者：
Watanabe, Sumiko
中科院分区：
文献类型：
--
作者：
Usui, Ayumi;Mochizuki, Yujin;Watanabe, Sumiko
Sry相关的HMG盒（Sox）蛋白，Sox11和Sox4是SoxC亚型的成员。我们发现Sox 11在早期视网膜祖细胞中强烈表达，Sox 4在出生前后开始表达，此时Sox 11的表达消退。为了分析Sox 11和Sox 4在视网膜发育中的作用，我们干扰了它们在视网膜外植体培养物中的表达模式。在视网膜祖细胞中过表达Sox 11和Sox 4导致相似的表型：视锥细胞数量增加，视杆细胞和Muller胶质细胞数量显著减少。最新的分析表明，锥细胞产生在一个较晚的发展阶段比，在锥发生正常发生。Sox11基因敲除的视网膜在胚胎期表现出延迟的发病和视网膜细胞亚群分化的进展。出生后，视网膜分化相对正常地发生，可能是因为Sox 4的多余活性，它在出生前后开始表达。过表达和功能丧失分析未能提供任何证据表明Sox11和Sox4直接调节对视网膜细胞亚群分化至关重要的基因的转录。然而，一些早期前神经基因的组蛋白H3乙酰化在敲除视网膜中减少。因此，Sox 11可能会产生一种表观遗传状态，有助于建立分化能力。综合我们的研究结果，我们提出视网膜发生过程中Sox 11和Sox 4的顺序表达通过帮助建立视网膜祖细胞的能力而导致视网膜分化的微调。
Sry-related HMG box (Sox) proteins, Sox11 and Sox4 are members of the SoxC subtype. We found that Sox11 was strongly expressed in early retinal progenitor cells and that Sox4 expression began around birth, when expression of Sox11 subsided. To analyze the roles of Sox11 and Sox4 in retinal development, we perturbed their expression patterns in retinal explant cultures. Overexpression of Sox11 and Sox4 in retinal progenitors resulted in similar phenotypes: an increased number of cone cells and dramatically decreased numbers of rod cells and Muller glia. Birth-date analysis showed that cone cells were produced at a later developmental stage than that in which cone genesis normally occurs. Sox11-knockout retinas showed delayed onset and progress of differentiation of subsets of retinal cells during the embryonic period. After birth, retinal differentiation took place relatively normally, probably because of the redundant activity of Sox4, which starts to be expressed around birth. Overexpression and loss-of-function analysis failed to provide any evidence that Sox11 and Sox4 directly regulate the transcription of genes crucial to the differentiation of subsets of retinal cells. However, histone H3 acetylation of some early proneural genes was reduced in knockout retina. Thus, Sox11 may create an epigenetic state that helps to establish the competency to differentiate. Taking our findings together, we propose that the sequential expression of Sox11 and Sox4 during retinogenesis leads to the fine adjustment of retinal differentiation by helping to establish the competency of retinal progenitors.