The genetic hierarchy that controls myelination of peripheral nerves by Schwann cells includes the POU domain Oct-6/Scip/Tst-1and the zinc-finger Krox-20/Egr2 transcription factors. These pivotal transcription factors act to control the onset of myelination during development and tissue regeneration in adults following damage. In this report we demonstrate the involvement of a third transcription factor, the POU domain factor Brn-2. We show that Schwann cells express Brn-2 in a developmental profile similar to that of Oct-6 and that Brn-2 gene activation does not depend on Oct-6. Overexpression of Brn-2 in Oct-6-deficient Schwann cells, under control of the Oct-6 Schwann cell enhancer (SCE), results in partial rescue of the developmental delay phenotype, whereas compound disruption of both Brn-2 and Oct-6 results in a much more severe phenotype. Together these data strongly indicate that Brn-2 function largely overlaps with that of Oct-6 in driving the transition from promyelinating to myelinating Schwann cells.

*Gene Expression Regulation, Developmental, Animals, Base Sequence, Cell Differentiation/genetics/*physiology, Chick Embryo, Cloning, Molecular, DNA Primers, DNA-Binding Proteins/genetics/metabolism, Embryonic and Fetal Development, Enhancer Elements (Genetics), Exons, Gene Deletion, Genes, Reporter, Homeodomain Proteins/genetics/metabolism, Mice, Mice, Transgenic, Morphogenesis, Myelin Sheath/physiology, Octamer Transcription Factor-6, POU Domain Factors, Polymerase Chain Reaction, Promoter Regions (Genetics), Recombinant Proteins/metabolism, Research Support, Non-U.S. Gov't, Restriction Mapping, Schwann Cells/*physiology, Transcription Factors/*genetics/metabolism
dx.doi.org/10.1101/gad.258203, hdl.handle.net/1765/13163
Genes & Development
Erasmus MC: University Medical Center Rotterdam

Jaegle, M.M, Ghazvini, M, Mandemakers, W.J, Piirsoo, M, Driegen, M.J.F, Levavasseur, F, … Meijer, D. (2003). The POU proteins Brn-2 and Oct-6 share important functions in Schwann cell development. Genes & Development, 1380–1391. doi:10.1101/gad.258203