Institut für Biochemie, Emil-Fischer-Zentrum, Universität Erlangen-Nürnberg, D-91054 Erlangen, Germany.
Development. 2014 Jan;141(1):39-50. doi: 10.1242/dev.098418. Epub 2013 Nov 20.
Neural precursor cells of the ventricular zone give rise to all neurons and glia of the central nervous system and rely for maintenance of their precursor characteristics on the closely related SoxB1 transcription factors Sox1, Sox2 and Sox3. We show in mouse spinal cord that, whereas SoxB1 proteins are usually downregulated upon neuronal specification, they continue to be expressed in glial precursors. In the oligodendrocyte lineage, Sox2 and Sox3 remain present into the early phases of terminal differentiation. Surprisingly, their deletion does not alter precursor characteristics but interferes with proper differentiation. Although a direct influence on myelin gene expression may be part of their function, we provide evidence for another mode of action. SoxB1 proteins promote oligodendrocyte differentiation in part by negatively controlling miR145 and thereby preventing this microRNA from inhibiting several pro-differentiation factors. This study presents one of the few cases in which SoxB1 proteins, including the stem cell factor Sox2, are associated with differentiation rather than precursor functions.
脑室区的神经前体细胞产生中枢神经系统的所有神经元和神经胶质细胞，并且依赖于密切相关的 SoxB1 转录因子 Sox1、Sox2 和 Sox3 来维持其前体细胞特征。我们在小鼠脊髓中表明，尽管 SoxB1 蛋白通常在神经元特化后下调，但它们在神经胶质前体细胞中继续表达。在少突胶质细胞谱系中，Sox2 和 Sox3 持续存在于终末分化的早期阶段。令人惊讶的是，它们的缺失不会改变前体细胞的特征，但会干扰正常的分化。尽管 SoxB1 蛋白对髓鞘基因表达的直接影响可能是其功能的一部分，但我们提供了另一种作用模式的证据。SoxB1 蛋白通过负调控 miR145 促进少突胶质细胞分化，从而防止该 microRNA 抑制几种促分化因子。这项研究提出了 SoxB1 蛋白（包括干细胞因子 Sox2）与分化而不是前体细胞功能相关的少数情况之一。
