Sox2-Deficient Müller Glia Disrupt the Structural and Functional Maturation of the Mammalian Retina.
Sox2-Deficient Müller Glia Disrupt the Structural and Functional Maturation of the Mammalian Retina.
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DOI：
10.1167/iovs.15-17994
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发表时间：
2016-03
影响因子：
4.4
通讯作者：
Weiss ER
中科院分区：
文献类型：
--
作者：
Bachleda AR;Pevny LH;Weiss ER
椎动物视网膜的主要神经胶质细胞<s:1>勒胶质细胞（MG）具有静止祖细胞的特征。它们表达关键的祖细胞标记，包括高迁移率群盒转录因子SOX2，并保持祖细胞样形态。在胚胎和成熟中枢神经系统中，SOX2维持神经干细胞的身份。然而，其在神经胶质细胞中的功能尚未确定。我们在MG发生高峰期对Sox2进行诱导的MG特异性基因消融，分析其在小鼠MG成熟中的功能以及对视网膜其他细胞的影响。在出生后发育的关键阶段对sox2缺陷视网膜进行组织学和功能分析。出生后视网膜中Sox2的消融导致内丛状层MG突的紊乱和核层细胞体的错位。这种紊乱与神经视网膜变薄和内外丛状层神经元过程的破坏同时发生。视网膜电图功能分析显示b波振幅降低。因此，Sox2消融导致MG成熟中断对视网膜功能产生负面影响。这些结果证明了SOX2在胶质细胞生长和粘附过程中的新作用，并为<s:1> ller胶质细胞在视网膜细胞结构发育中的重要作用提供了新的见解。在此之前，已知SOX2在决定细胞命运中起主要作用。我们的实验绕过细胞命运转换，确立了SOX2在既定细胞谱系中的新作用。
Müller glia (MG), the principal glial cells of the vertebrate retina, display quiescent progenitor cell characteristics. They express key progenitor markers, including the high mobility group box transcription factor SOX2 and maintain a progenitor-like morphology. In the embryonic and mature central nervous system, SOX2 maintains neural stem cell identity. However, its function in committed Müller glia has yet to be determined. We use inducible, MG-specific genetic ablation of Sox2 in vivo at the peak of MG genesis to analyze its function in the maturation of murine MG and effects on other cells in the retina. Histologic and functional analysis of the Sox2-deficient retinas is conducted at key points in postnatal development. Ablation of Sox2 in the postnatal retina results in disorganization of MG processes in the inner plexiform layer and mislocalized cell bodies in the nuclear layers. This disorganization is concurrent with a thinning of the neural retina and disruption of neuronal processes in the inner and outer plexiform layers. Functional analysis by electroretinography reveals a decrease in the b-wave amplitude. Disruption of MG maturation due to Sox2 ablation therefore negatively affected the function of the retina. These results demonstrate a novel role for SOX2 in glial process outgrowth and adhesion, and provide new insights into the essential role Müller glia play in the development of retinal cytoarchitecture. Prior to this work, SOX2 was known to have a primary role in determining cell fate. Our experiments bypass cell fate conversion to establish a new role for SOX2 in a committed cell lineage.