Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children/UC Davis School of Medicine, Sacramento, CA, 95817, USA.
Department of Neurology, School of Medicine, UC Davis, Davis, CA, 95817, USA.
Mol Neurobiol. 2018 Dec;55(12):9001-9015. doi: 10.1007/s12035-018-1035-7. Epub 2018 Apr 5.
Myelination in the central nervous system takes place predominantly during the postnatal development of humans and rodents by myelinating oligodendrocytes (OLs), which are differentiated from oligodendrocyte progenitor cells (OPCs). We recently reported that Sox2 is essential for developmental myelination in the murine brain and spinal cord. It is still controversial regarding the role of Sox2 in oligodendroglial lineage progression in the postnatal murine spinal cord. Analyses of a series of cell- and stage-specific Sox2 mutants reveal that Sox2 plays a biphasic role in regulating oligodendroglial lineage progression in the postnatal murine spinal cord. Sox2 controls the number of OPCs for subsequent differentiation through regulating their proliferation. In addition, Sox2 regulates the timing of OL differentiation and modulates the rate of oligodendrogenesis. Our experimental data prove that Sox2 is an intrinsic positive timer of oligodendroglial lineage progression and suggest that interventions affecting oligodendroglial Sox2 expression may be therapeutic for overcoming OPC differentiation arrest in dysmyelinating and demyelinating disorders.
中枢神经系统的髓鞘形成主要发生在人类和啮齿动物的出生后发育过程中，由少突胶质细胞（OL）完成，OL 由少突胶质前体细胞（OPC）分化而来。我们最近报道 Sox2 对于鼠脑和脊髓的发育性髓鞘形成是必需的。然而，Sox2 在出生后鼠脊髓中的少突胶质谱系进展中的作用仍存在争议。对一系列细胞和阶段特异性 Sox2 突变体的分析表明，Sox2 在调节出生后鼠脊髓中的少突胶质谱系进展中发挥双重作用。Sox2 通过调节其增殖来控制随后分化的 OPC 的数量。此外，Sox2 调节 OL 分化的时间，并调节少突胶质生成的速度。我们的实验数据证明 Sox2 是少突胶质谱系进展的内在正计时器，并表明影响少突胶质 Sox2 表达的干预措施可能对克服脱髓鞘和脱髓鞘疾病中的 OPC 分化阻滞具有治疗作用。
