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

Deniz Gökbuget1, Jorge A Pereira1, Sven Bachofner1

  • 1Department of Biology, Institute of Molecular Health Sciences, ETH Zurich, Otto-Stern-Weg 7, 8093 Zurich, Switzerland.

Nature Communications
|October 15, 2015
PubMed

Insights

The Lin28B/let-7 axis critically drives peripheral nervous system (PNS) myelination by regulating Schwann cell differentiation. This pathway

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • MicroRNAs (miRNAs) are key regulators of peripheral nervous system (PNS) myelination.
  • The specific miRNAs and mechanisms governing PNS myelination remain largely uncharacterized.

Purpose of the Study:

  • To identify the miRNAs involved in PNS myelination and elucidate their regulatory mechanisms.
  • To investigate the role of the Lin28B/let-7 axis in Schwann cell myelination.

Main Methods:

  • Analysis of miRNA and Lin28B expression during PNS myelination.
  • Utilized transgenic mouse models and cell culture systems to study myelination.
  • Investigated the downstream targets of let-7 miRNAs, including Krox20 and Notch signaling.

Main Results:

  • let-7 miRNAs are highly abundant during PNS myelination, inversely correlated with Lin28B expression.
  • Sustained Lin28B expression leads to reduced let-7 levels and impaired Schwann cell myelination.
  • let-7 miRNAs promote Krox20 expression and suppress inhibitory Notch signaling, facilitating myelination.

Conclusions:

  • The Lin28B/let-7 axis is a critical regulator of PNS myelination, particularly controlling its onset.
  • This pathway represents a potential therapeutic target for demyelinating diseases.

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