中国神经再生研究(英文版) ›› 2017, Vol. 12 ›› Issue (8): 1241-1246.doi: 10.4103/1673-5374.213537

• 综述:神经损伤修复保护与再生 • 上一篇    下一篇

雪旺细胞发育和神经再生中的转录抑制

  

  • 收稿日期:2017-06-28 出版日期:2017-08-15 发布日期:2017-08-15

Transcriptional inhibition in Schwann cell development and nerve regeneration

Susanne Quintes1, 2, Bastian G. Brinkmann1   

  1. 1 Max-Planck-Institute of Experimental Medicine, Department of Neurogenetics, Göttingen, Germany; 2 Department of Clinical Neurophysiology, University Medical Center Göttingen (UMG), Göttingen, Germany
  • Received:2017-06-28 Online:2017-08-15 Published:2017-08-15
  • Contact: Bastian G. Brinkmann, M.D.,brinkmann@em.mpg.de.

摘要:

雪旺细胞属于周围神经的胶质细胞,会形成富含脂质的髓鞘包裹周围神经轴突。周围神经损伤后,在一定程度上,雪旺细胞显示出明显的可塑性,这是神经再生成功的先决条件。

未成熟雪旺细胞的分化至最终成熟的髓鞘化和非髓鞘化的雪旺细胞受一组转录因子的紧密调节。转录激活雪旺细胞发育和损伤后的再分化伴随着负成熟抑制剂的失活,包括Sox2,Pax3,Id2,c-Jun和Notch。已知Sox2,Id2和Pax3可体外抑制髓磷脂基因表达,并且在雪旺细胞中促进c-Jun表达,抑制神经元和雪旺细胞共培养物中的髓鞘形成。髓鞘形成的这些负调节因子在成熟的雪旺细胞中不存在或以表达水平非常低。在雪旺细胞发育期间应及时抑制分化抑制剂,从而促进髓鞘再生。

orcid:0000-0002-7177-5749(Susanne Quintes)
0000-0003-1482-2788(Bastian G. Brinkmann)

Abstract:

Schwann cells, the myelinating glial cells of the peripheral nervous system are remarkably plastic after nerve trauma. Their transdifferentiation into specialized repair cells after injury shares some features with their development from the neural crest. Both processes are governed by a tightly regulated balance between activators and inhibitors to ensure timely lineage progression and allow re-maturation after nerve injury. Functional recovery after injury is very successful in rodents, however, in humans, lack of regeneration after nerve trauma and loss of function as the result of peripheral neuropathies represents a significant  problem. Our understanding of the basic molecular machinery underlying Schwann cell maturation and plasticity has made significant progress in recent years and novel players have been discovered. While the transcriptional activators of Schwann cell development and nerve repair have been well defined, the mechanisms counteracting negative regulation of (re-)myelination are less well understood. Recently, transcriptional inhibition has emerged as a new regulatory mechanism in Schwann cell development and nerve repair. This mini-review summarizes some of the regulatory mechanisms controlling both processes and the novel concept of “inhibiting the inhibitors” in the context of Schwann cell plasticity.

Key words: Schwann cell, Zeb2, myelin, transcription factors, regeneration, remyelination, neuropathy