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Egr2-dependent microRNA-138 is dispensable for peripheral nerve myelination

Hsin-Pin Lin1, Idil Oksuz1, John Svaren2

  • 1Department of Neurology and Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.

Scientific Reports
|March 2, 2018
PubMed

Insights

MicroRNAs are vital for peripheral nerve myelination. This study found that miR-138 is Egr2-dependent but not essential for Schwann cell myelination, despite its altered expression during development and injury.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • MicroRNAs (miRNAs) play a critical role in peripheral nerve myelination.
  • Previous studies focused on miRNA synthesis machinery, with limited investigation into individual miRNAs like miR-138.
  • miR-138 levels are reduced in Dicer1 and Dgcr8 knockout mice exhibiting hypomyelination.

Purpose of the Study:

  • To investigate the specific role of miR-138 in Schwann cell differentiation and peripheral nerve myelination.
  • To identify the regulatory mechanisms controlling miR-138 expression in Schwann cells.

Main Methods:

  • Analysis of miR-138 expression in Schwann cells during development and nerve injury.
  • Investigating the transcriptional regulation of the mir-138-1 locus by transcription factors EGR2 and SOX10.
  • Utilizing conditional knockout mouse models to assess the in vivo function of miR-138 in myelination.

Main Results:

  • The mir-138-1 locus is the primary source of miR-138 in Schwann cells and is upregulated during myelination, downregulated upon nerve injury.
  • EGR2 is essential for mir-138-1 transcription, with both EGR2 and SOX10 binding to a regulatory enhancer.
  • Conditional knockout of miR-138 did not significantly impact Schwann cell proliferation, cell cycle exit, or myelination.

Conclusions:

  • miR-138 is an Egr2-dependent microRNA regulated during myelination and nerve injury.
  • Despite its regulation, miR-138 is dispensable for peripheral nerve myelination in vivo.

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