Stem cell factor Sox2 and its close relative Sox3 have differentiation functions in oligodendrocytes

Development. 2014 Jan;141(1):39-50. doi: 10.1242/dev.098418. Epub 2013 Nov 20.

Abstract

Neural precursor cells of the ventricular zone give rise to all neurons and glia of the central nervous system and rely for maintenance of their precursor characteristics on the closely related SoxB1 transcription factors Sox1, Sox2 and Sox3. We show in mouse spinal cord that, whereas SoxB1 proteins are usually downregulated upon neuronal specification, they continue to be expressed in glial precursors. In the oligodendrocyte lineage, Sox2 and Sox3 remain present into the early phases of terminal differentiation. Surprisingly, their deletion does not alter precursor characteristics but interferes with proper differentiation. Although a direct influence on myelin gene expression may be part of their function, we provide evidence for another mode of action. SoxB1 proteins promote oligodendrocyte differentiation in part by negatively controlling miR145 and thereby preventing this microRNA from inhibiting several pro-differentiation factors. This study presents one of the few cases in which SoxB1 proteins, including the stem cell factor Sox2, are associated with differentiation rather than precursor functions.

Keywords: Glia; High mobility group; MicroRNA; Myelin; Transcriptional control.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Line
  • Gene Expression Regulation, Developmental
  • HEK293 Cells
  • Humans
  • Mice
  • MicroRNAs / genetics*
  • Neural Stem Cells
  • Neurogenesis
  • Neuroglia / cytology
  • Neuroglia / metabolism
  • Oligodendroglia / metabolism*
  • Promoter Regions, Genetic
  • Rats
  • SOX9 Transcription Factor / biosynthesis
  • SOX9 Transcription Factor / metabolism*
  • SOXB1 Transcription Factors / metabolism*
  • Spinal Cord / cytology
  • Spinal Cord / embryology
  • Spinal Cord / metabolism

Substances

  • MIRN145 microRNA, mouse
  • MicroRNAs
  • SOX9 Transcription Factor
  • SOXB1 Transcription Factors
  • Sox2 protein, mouse
  • Sox3 protein, mouse
  • Sox9 protein, mouse