The POU gene Brn-5 is induced by neuregulin and is restricted to myelinating Schwann cells.
The POU family of transcription factors plays a vital role in controlling cell-fate determination and the timing of cellular events in a number of tissues, including the nervous system. One such POU protein, SCIP, is expressed by Schwann cells in a tightly delimited developmental window termed promyelination. In the PNS, promyelination is functionally defined as the period following Schwann cell exit from the cell-cycle, but prior to the onset of myelination. Previous transgenic and gene ablation studies have shown that SCIP is a myelin-competence factor in the Schwann cell, where it is required for entry into, and the subsequent maintenance of promyelination. To further understand the molecular biology of the promyelination-to-myelination transition in the Schwann cell, we have undertaken a series of DDRTPCR studies to identify genes that are expressed during this phenotypic flux. Through these studies we have identified another POU gene, Brn-5, the expression of which has not previously been appreciated in the Schwann cell. Here we show that the developmental expression patterns of Brn-5 and SCIP are inverse, with Brn-5 stably expressed in the adult myelinating Schwann cell, but virtually absent during promyelination. Further, we show that the induction of the two genes is independent, with SCIP induction requiring activation of adenyl cyclase, whereas Brn-5 induction requires only GGF2. In addition, the induction of Brn-5 is exquisitely sensitive to neuregulin concentration, with higher levels inhibiting its expression. Following nerve injury, when GGF2 levels are elevated in the distal nerve, Brn-5 expression disappears, and SCIP is reexpressed.
Wu
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R
Department of Neuroscience, Department of Pathology, Comprehensive Cancer Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, 10461
Jurek
M
M
Sundarababu
S
S
Weinstein
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DE
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D009409:Nerve Crush; D020890:Neuregulin-1 / Q000494:pharmacology*; D050816:Octamer Transcription Factor-6; D050809:POU Domain Factors; D012583:Schwann Cells / Q000166:cytology* / Q000502:physiology*; D012584:Sciatic Nerve / Q000166:cytology / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics*; D014855:Wallerian Degeneration / Q000503:physiopathology
D004268:DNA-Binding Proteins; D020890:Neuregulin-1; D050809:POU Domain Factors; C494180:Pou3f1 protein, mouse; C489996:Pou6f1 protein, mouse; D014157:Transcription Factors; D050816:Octamer Transcription Factor-6