| First Author | Gökbuget D | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 8584 | PubMed ID | 26466203 |
| Mgi Jnum | J:227632 | Mgi Id | MGI:5702345 |
| Doi | 10.1038/ncomms9584 | Citation | Gokbuget D, et al. (2015) The Lin28/let-7 axis is critical for myelination in the peripheral nervous system. Nat Commun 6:8584 |
| abstractText | 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. |
