Prolonged Sox4 expression in oligodendrocytes interferes with normal myelination in the central nervous system


  • M.R. Potzner
  • C. Griffel
  • E. Luetjen-Drecoll
  • M.R. Boesl
  • M. Wegner
  • E. Sock


  • Molecular and Cellular Biology


  • Mol Cell Biol 27 (15): 5316-5326


  • The highly related transcription factors Sox4 and Sox11 are both expressed in oligodendrocyte precursors. Yet, it is unknown whether they have a function in oligodendrocyte development. By overexpressing Sox4 under the control of 3.1 kb of MBP 5' flanking sequences in transgenic mice, we extended Sox4 expression in the oligodendrocyte lineage from oligodendrocyte precursors to cells undergoing terminal differentiation. As a consequence of transgene expression, mice develop the full spectrum of phenotypic traits associated with a severe hypomyelination during the first postnatal weeks. Myelin gene expression was severely reduced and myelin dramatically thinned in several CNS regions. Despite these disturbances in CNS myelination, the number of oligodendrocytic cells remained unaltered. Considering that apoptosis rates were normal and proliferation only slightly increased, oligodendrocytes likely persist in a premyelinating to early myelinating state. This shows that prolonged Sox4 expression in cells of the oligodendrocyte lineage is incompatible with the acquisition of a fully mature phenotype and argues that the presence of Sox4, and possibly Sox11, in oligodendrocyte precursors may normally prevent premature differentiation.