Roberts Sheridan L, Dun Xin-Peng, Doddrell Robin D S, Mindos Thomas, Drake Louisa K, Onaitis Mark W, Florio Francesca, Quattrini Angelo, Lloyd Alison C, D'Antonio Maurizio, Parkinson David B
Plymouth University Peninsula Schools of Medicine and Dentistry, John Bull Building, Plymouth Science Park, Plymouth PL6 8BU, UK.
University of Bath, Bath BA2 7AY, UK.
Development. 2017 Sep 1;144(17):3114-3125. doi: 10.1242/dev.150656. Epub 2017 Jul 25.
Correct myelination is crucial for the function of the peripheral nervous system. Both positive and negative regulators within the axon and Schwann cell function to ensure the correct onset and progression of myelination during both development and following peripheral nerve injury and repair. The Sox2 transcription factor is well known for its roles in the development and maintenance of progenitor and stem cell populations, but has also been proposed as a negative regulator of myelination in Schwann cells. We wished to test fully whether Sox2 regulates myelination and show here that, in mice, sustained Sox2 expression blocks myelination in the peripheral nerves and maintains Schwann cells in a proliferative non-differentiated state, which is also associated with increased inflammation within the nerve. The plasticity of Schwann cells allows them to re-myelinate regenerated axons following injury and we show that re-myelination is also blocked by Sox2 expression in Schwann cells. These findings identify Sox2 as a physiological regulator of Schwann cell myelination and its potential to play a role in disorders of myelination in the peripheral nervous system.
正确的髓鞘形成对于周围神经系统的功能至关重要。轴突和施万细胞内的正向和负向调节因子共同作用，以确保在发育过程以及周围神经损伤和修复后髓鞘形成的正确起始和进程。Sox2转录因子以其在祖细胞和干细胞群体的发育和维持中的作用而闻名，但也有人提出它是施万细胞髓鞘形成的负向调节因子。我们希望全面测试Sox2是否调节髓鞘形成，并在此表明，在小鼠中，持续的Sox2表达会阻断周围神经的髓鞘形成，并使施万细胞维持在增殖性未分化状态，这也与神经内炎症增加有关。施万细胞的可塑性使它们能够在损伤后重新髓鞘化再生的轴突，并且我们表明施万细胞中的Sox2表达也会阻断重新髓鞘化。这些发现确定Sox2是施万细胞髓鞘形成的生理调节因子，及其在周围神经系统髓鞘形成障碍中发挥作用的潜力。
