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 c ell-fate determination and the timing of cellular events in a number of tis sues, including the nervous system. One such POU protein, SCIP, is expresse d by Schwann cells in a tightly delimited developmental window termed promy elination. 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 requir ed for entry into, and the subsequent maintenance of promyelination. To fur ther understand the molecular biology of the promyelination-to-myelination transition in the Schwann cell, we have undertaken a series of DDRTPCR stud ies to identify genes that are expressed during this phenotypic flux. Throu gh these studies we have identified another POLI gene, Brn-5, the expressio n 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 inve rse, with Brn-5 stably expressed in the adult myelinating Schwann cell, but virtually absent during promyelination. Further, we show that the inductio n 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 concentrati on, with higher levels inhibiting its expression. Following nerve injury, w hen GGF2 levels are elevated in the distal nerve, Brn-5 expression disappea rs, and SCIP is reexpressed.