Division of Molecular and Developmental Biology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Development. 2013 Feb;140(4):740-50. doi: 10.1242/dev.090274. Epub 2013 Jan 14.
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 Müller 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.
Sry 相关高迁移率族框（Sox）蛋白 Sox11 和 Sox4 是 SoxC 亚类的成员。我们发现 Sox11 在早期视网膜祖细胞中强烈表达，而 Sox4 的表达始于出生时，此时 Sox11 的表达减弱。为了分析 Sox11 和 Sox4 在视网膜发育中的作用，我们在视网膜外植体培养物中干扰了它们的表达模式。视网膜祖细胞中 Sox11 和 Sox4 的过表达导致相似的表型：视锥细胞数量增加，视杆细胞和 Muller 胶质细胞数量急剧减少。出生日期分析表明，视锥细胞的产生晚于正常发生的视锥细胞发生的阶段。Sox11 敲除视网膜在胚胎期显示出视网膜细胞亚群分化的起始和进展延迟。出生后，视网膜分化相对正常进行，可能是由于 Sox4 的冗余活性所致，Sox4 大约在出生时开始表达。过表达和功能丧失分析均未提供任何证据表明 Sox11 和 Sox4 直接调控对视网膜细胞亚群分化至关重要的基因的转录。然而，一些早期神经前体细胞基因的组蛋白 H3 乙酰化在敲除视网膜中减少。因此，Sox11 可能会创建一种有助于建立分化能力的表观遗传状态。综合我们的发现，我们提出 Sox11 和 Sox4 在视网膜发生过程中的顺序表达通过帮助建立视网膜祖细胞的分化能力来精细调节视网膜分化。
