Regulation of the myelin gene periaxin provides evidence for Krox-20-independent myelin-related signalling in Schwann cells.
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.
Parkinson
David B
DB
Department of Anatomy and Developmental Biology, University College London, Gower Street, UK.
Dickinson
Sarah
S
Bhaskaran
Ambily
A
Kinsella
Matthew T
MT
Brophy
Peter J
PJ
Sherman
Diane L
DL
Sharghi-Namini
Soheila
S
Duran Alonso
Maria B
MB
Mirsky
Rhona
R
Jessen
Kristjan R
KR
D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051767:Early Growth Response Protein 2; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D016296:Mutagenesis / Q000502:physiology; D009186:Myelin Sheath / Q000378:metabolism*; D009363:Neoplasm Proteins; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012583:Schwann Cells / Q000166:cytology / Q000378:metabolism*; D012584:Sciatic Nerve / Q000166:cytology / Q000254:growth & development / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D051767:Early Growth Response Protein 2; C497327:Egr2 protein, mouse; C497328:Egr2 protein, rat; D008565:Membrane Proteins; C099945:Nab2 protein, mouse; C490999:Nab2 protein, rat; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; C086745:periaxin; D000242:Cyclic AMP