The Lin28/let-7 axis is critical for myelination in the peripheral nervous system.
Nat Commun
; 6: 8584, 2015 Oct 14.
Article
em En
| MEDLINE
| ID: mdl-26466203
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Sistema Nervoso Periférico
/
MicroRNAs
/
Proteínas de Ligação a DNA
/
Proteína 2 de Resposta de Crescimento Precoce
/
Bainha de Mielina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Commun
Assunto da revista:
BIOLOGIA
/
CIENCIA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Suíça