Regulation of the Myelin Gene Periaxin Provides Evidence for Krox-20-independent Myelin-Related Signalling in Schwann Cells

Mol Cell Neurosci. 2003 May;23(1):13-27. doi: 10.1016/s1044-7431(03)00024-1.

Abstract

We investigated the role of Krox-20 (Egr2), a transcription factor that regulates myelination, in controlling the myelin-associated protein periaxin. In developing Schwann cells, periaxin immunoreactivity appeared at least 2 days before Krox-20-immunopositive nuclei. Consistent with this, in Krox-20 null mice periaxin was upregulated on schedule, albeit to a lower level. In culture Krox-20 and periaxin were upregulated by cAMP as expected for myelin genes. Only those cells with the highest periaxin levels also expressed Krox-20, while other periaxin-positive cells remained Krox-20-negative. Furthermore, cAMP elevated periaxin even in Krox-20 null cells. We also found that in culture enforced Krox-20 expression induced expression of periaxin mRNA and protein in the absence of cAMP elevating agents, and that this induction was inhibited by the co-repressor NAB2. These findings reveal a dual mechanism for periaxin regulation and suggest that the role of Krox-20 is to amplify an earlier Krox-20-independent activation of the periaxin gene. Thus the axonal signals responsible for myelination are only partially transduced in Schwann cells by mechanisms that depend on Krox-20.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Cyclic AMP / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Early Growth Response Protein 2
  • Gene Expression Regulation, Developmental / physiology
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Knockout
  • Mutagenesis / physiology
  • Myelin Sheath / metabolism*
  • Neoplasm Proteins*
  • RNA, Messenger / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Schwann Cells / cytology
  • Schwann Cells / metabolism*
  • Sciatic Nerve / cytology
  • Sciatic Nerve / growth & development
  • Sciatic Nerve / physiology
  • Signal Transduction / physiology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • DNA-Binding Proteins
  • Early Growth Response Protein 2
  • Egr2 protein, mouse
  • Egr2 protein, rat
  • Membrane Proteins
  • Nab2 protein, mouse
  • Nab2 protein, rat
  • Neoplasm Proteins
  • RNA, Messenger
  • Repressor Proteins
  • Transcription Factors
  • periaxin
  • Cyclic AMP