The Lin28/let-7 axis is critical for myelination in the peripheral nervous system

Nat Commun. 2015 Oct 14:6:8584. doi: 10.1038/ncomms9584.


MicroRNAs (miRNAs) are crucial regulators of myelination in the peripheral nervous system (PNS). However, the miRNAs species involved and the underlying mechanisms are largely unknown. We found that let-7 miRNAs are highly abundant during PNS myelination and that their levels are inversely correlated to the expression of lin28 homolog B (Lin28B), an antagonist of let-7 accumulation. Sustained expression of Lin28B and consequently reduced levels of let-7 miRNAs results in a failure of Schwann cell myelination in transgenic mouse models and in cell culture. Subsequent analyses revealed that let-7 miRNAs promote expression of the myelination-driving master transcription factor Krox20 (also known as Egr2) through suppression of myelination inhibitory Notch signalling. We conclude that the Lin28B/let-7 axis acts as a critical driver of PNS myelination, in particular by regulating myelination onset, identifying this pathway also as a potential therapeutic target in demyelinating diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • DNA-Binding Proteins / metabolism*
  • Early Growth Response Protein 2 / metabolism*
  • HEK293 Cells
  • Humans
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • MicroRNAs / metabolism*
  • Myelin Sheath / metabolism*
  • Peripheral Nervous System / metabolism*
  • RNA-Binding Proteins
  • Rats
  • Receptors, Notch / metabolism
  • Ribonuclease III / metabolism


  • DNA-Binding Proteins
  • Early Growth Response Protein 2
  • Lin28b protein, mouse
  • MicroRNAs
  • RNA-Binding Proteins
  • Receptors, Notch
  • mirnlet7 microRNA, mouse
  • Ribonuclease III

Associated data

  • GEO/GSE64562