The transcription factors Sox10 and Myrf define an essential regulatory network module in differentiating oligodendrocytes

PLoS Genet. 2013 Oct;9(10):e1003907. doi: 10.1371/journal.pgen.1003907. Epub 2013 Oct 31.

Abstract

Myelin is essential for rapid saltatory conduction and is produced by Schwann cells in the peripheral nervous system and oligodendrocytes in the central nervous system. In both cell types the transcription factor Sox10 is an essential component of the myelin-specific regulatory network. Here we identify Myrf as an oligodendrocyte-specific target of Sox10 and map a Sox10 responsive enhancer to an evolutionarily conserved element in intron 1 of the Myrf gene. Once induced, Myrf cooperates with Sox10 to implement the myelination program as evident from the physical interaction between both proteins and the synergistic activation of several myelin-specific genes. This is strongly reminiscent of the situation in Schwann cells where Sox10 first induces and then cooperates with Krox20 during myelination. Our analyses indicate that the regulatory network for myelination in oligodendrocytes is organized along similar general principles as the one in Schwann cells, but is differentially implemented.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics*
  • Cell Line
  • Central Nervous System / growth & development
  • Central Nervous System / metabolism
  • Early Growth Response Protein 2 / genetics*
  • Early Growth Response Protein 2 / metabolism
  • Gene Expression Regulation, Developmental
  • Gene Regulatory Networks*
  • High Mobility Group Proteins / genetics
  • Humans
  • Mice
  • Mice, Transgenic
  • Myelin Sheath / genetics
  • Myelin Sheath / metabolism
  • Oligodendroglia / metabolism
  • SOXE Transcription Factors / genetics*
  • Schwann Cells / metabolism*
  • Transcription Factors / genetics*

Substances

  • Early Growth Response Protein 2
  • High Mobility Group Proteins
  • SOXE Transcription Factors
  • Sox10 protein, mouse
  • Transcription Factors
  • myelin gene regulatory factor, mouse

Grant support

This work was supported by a grant from the Deutsche Forschungsgemeinschaft (We1326/11) to MW. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.