Abstract：
The high-mobility-group domain-containing transcription factor Sox9 confers glial competence to neuroepithelial precursors in the developing central nervous system and is an important determinant of astroglial and oligodendroglial specification. In oligodendroglial cells, it remains expressed in oligodendrocyte progenitor cells (OPCs) of the developing nervous system, but is shut off in differentiating oligodendrocytes as well as in OPCs that persist in the adult nervous system. To better understand the role of Sox9 in OPCs, we generated mouse models that allowed oligodendroglial expression of a Sox9 transgene during development or in the adult. With transgene expression beginning in the last trimester of pregnancy, the number of OPCs increased dramatically, followed by comparable gains in the number of pre-myelinating and myelinating oligodendrocytes as assessed by marker gene expression. This argues that Sox9 boosts oligodendrogenesis during ontogenetic development at all stages, including terminal oligodendrocyte differentiation. When Sox9 transgene expression started in the adult, many transgene-expressing OPCs failed to maintain their progenitor cell identity and instead converted into myelinating oligodendrocytes. As infrequent and inefficient differentiation of adult OPCs is one of the main obstacles to effective remyelination in demyelinating diseases such as Multiple Sclerosis, increased Sox9 levels in adult OPCs may substantially increase their remyelination capacity.
摘要：
含有高迁移率族结构域的转录因子Sox9赋予发育中的中枢神经系统中的神经上皮前体神经胶质能力，并且是星形胶质细胞和少突胶质细胞规格的重要决定因素。在少突胶质细胞中，它仍然在发育中的神经系统的少突胶质细胞祖细胞（OPCs）中表达，但是在分化少突胶质细胞以及在成人神经系统中持续存在的OPCs中被关闭。为了更好地理解Sox9在OPC中的作用，我们建立了小鼠模型，该模型允许在发育过程中或成体中少突胶质细胞表达Sox9转基因。随着转基因表达在怀孕的最后三个月开始，OPC的数量急剧增加，其次是通过标记基因表达评估的髓鞘形成前和髓鞘形成少突胶质细胞数量的相当增加。这认为Sox9在各个阶段的个体发育过程中促进少突形成，包括末端少突胶质细胞分化。当Sox9转基因在成人中开始表达时，许多表达转基因的OPC未能保持其祖细胞的身份,而是转化为髓鞘少突胶质细胞.由于成人OPCs的罕见和低效分化是在多发性硬化症等脱髓鞘疾病中有效髓鞘再生的主要障碍之一，成人OPCs中Sox9水平的升高可能会大大增加其髓鞘再生能力。
