Expression of the POU-domain transcription factors SCIP/Oct-6 and Brn-2 is associated with Schwann cell but not oligodendrocyte remyelination of the CNS.
The class III POU-domain transcription factor SCIP/Oct-6 is expressed by promyelinating Schwann cells and, in tissue culture, by oligodendrocyte progenitors (OPs), but is down-regulated in both cells types as they differentiate. Although the expression of SCIP/Oct-6 has been examined in peripheral nerve remyelination, its expression in CNS remyelination has not been addressed. Using a toxin model of demyelination, in which the demyelinated axons are remyelinated in an age-dependent manner by both oligodendrocytes and Schwann cells, we have compared the expression of SCIP/Oct-6 mRNA with that of an OP marker (PDGF-alphaR), a marker of myelinating oligodendrocytes (PLP), and markers of myelinating Schwann cells (P(0) and Krox-20) by in situ hybridization. We have found that the expression of SCIP/Oct-6 mRNA precedes that of P(0) and Krox-20 mRNA expression, but bears little correlation with the expression profiles of either PDGF-alphaR or PLP mRNA. Moreover, there is a spatial correlation between the expression SCIP/Oct-6 mRNA and that of P(0) but not of PDGF-alphaR. These results indicate that SCIP/Oct-6 expression following CNS demyelination is associated with Schwann cell and not oligodendrocyte remyelination. We have also shown that another POU-domain transcription factor, Brn-2, is expressed during CNS remyelination, but that like SCIP/Oct-6, it too has an expression profile indicating that it is associated with the Schwann cell component of remyelination. In addition, we show that Brn-2 expression in Schwann cells is not restricted to CNS remyelination but is also expressed in a similar manner to SCIP/Oct-6 during Schwann cell myelination of neonatal peripheral nerves and regenerating transected adult nerve and in cultured Schwann cells following induction of elevated cAMP levels.
Sim
Fraser J
FJ
Department of Clinical Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, United Kingdom.
Zhao
Chao
C
Li
Wen-Wu
WW
Lakatos
Andras
A
Franklin
Robin J M
RJ
D000818:Animals; D015415:Biomarkers; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D002460:Cell Line; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000378:metabolism; D004996:Ethidium / Q000494:pharmacology; D005260:Female; D018398:Homeodomain Proteins; D007425:Intracellular Membranes / Q000378:metabolism; D009186:Myelin Sheath / Q000187:drug effects / Q000502:physiology*; D050816:Octamer Transcription Factor-6; D009836:Oligodendroglia / Q000502:physiology; D050809:POU Domain Factors; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000502:physiology*; D012584:Sciatic Nerve / Q000502:physiology / Q000503:physiopathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D015415:Biomarkers; D018398:Homeodomain Proteins; D050809:POU Domain Factors; C494179:Pou3f1 protein, rat; D012333:RNA, Messenger; D014157:Transcription Factors; C085076:transcription factor Brn-2; D050816:Octamer Transcription Factor-6; D000242:Cyclic AMP; D004996:Ethidium