Identification of genes that are downregulated in the absence of the POU domain transcription factor pou3f1 (Oct-6, Tst-1, SCIP) in sciatic nerve.
Despite the importance of myelinating Schwann cells in health and disease, little is known about the genetic mechanisms underlying their development. The POU domain transcription factor pou3f1 (Tst-1, SCIP, Oct-6) is required for the normal differentiation of myelinating Schwann cells, but its precise role requires identification of the genes that it regulates. Here we report the isolation of six genes whose expression is reduced in the absence of pou3f1. Only one of these genes, the fatty acid transport protein P2, was known previously to be expressed in Schwann cells. The LIM domain proteins cysteine-rich protein-1 (CRP1) and CRP2 are expressed in sciatic nerve and induced by forskolin in cultured Schwann cells, but only CRP2 requires pou3f1 for normal expression. pou3f1 appears to require the claw paw gene product for activation of at least some of its downstream effector genes. Expression of the novel Schwann cell genes after nerve injury suggests that they are myelin related. One of the genes, tramdorin1, encodes a novel amino acid transport protein that is localized to paranodes and incisures. Our results suggest that pou3f1 functions to activate gene expression in the differentiation of myelinating Schwann cells.
Bermingham
John R
JR
McLaughlin Research Institute, Great Falls, Montana 59405, USA. jrbjr@po.mri.montana.edu
Shumas
Susan
S
Whisenhunt
Tom
T
Sirkowski
Erich E
EE
O'Connell
Shawn
S
Scherer
Steven S
SS
Rosenfeld
Michael G
MG
D048868:Adaptor Proteins, Signal Transducing; D026905:Amino Acid Transport Systems / Q000502:physiology; D000818:Animals; D030161:Avian Proteins; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D003599:Cytoskeleton / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D020869:Gene Expression Profiling; D060588:LIM Domain Proteins; D051379:Mice; D008817:Mice, Mutant Strains; D009186:Myelin Sheath / Q000378:metabolism; D050816:Octamer Transcription Factor-6; D017434:Protein Structure, Tertiary / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012584:Sciatic Nerve / Q000293:injuries / Q000378:metabolism*; D020426:Sciatic Neuropathy / Q000378:metabolism*; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D026905:Amino Acid Transport Systems; D030161:Avian Proteins; D022782:CCAAT-Enhancer-Binding Protein-beta; D002352:Carrier Proteins; D060588:LIM Domain Proteins; C494180:Pou3f1 protein, mouse; C494179:Pou3f1 protein, rat; D012333:RNA, Messenger; D014157:Transcription Factors; D050816:Octamer Transcription Factor-6; D005576:Colforsin