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RESEARCH PAPER

The POU proteins Brn-2 and Oct-6 share important functions in Schwann cell development

Departments of ¹ Cell Biology and Genetics and ² Neurosciences, Erasmus University Medical Center, 3000DR Rotterdam, Netherlands

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.

[Keywords: POU domain; myelin; Schwann cell; nerve development]

Received December 20, 2002; revised version accepted April 10, 2003.

⁴ Present address: National Institute of Chemical Physics and Biophysics, Tallinn EE0026, Estonia.

Corresponding author.

⁵ E-MAIL d.meijer{at}erasmusmc.nl; FAX 31-10-408-9468.

Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.258203.

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