A distal Schwann cell-specific enhancer mediates axonal regulation of the Oct-6 transcription factor during peripheral nerve development and regeneration

The POU domain transcription factor Oct-6 is a major regulator of Schwann c ell differentiation and myelination. During nerve development and regenerat ion, expression of Oct-6 is under the control of axonal signals. Identifica tion of the cis-acting elements necessary for Oct-6 gene regulation is an i mportant step in deciphering the complex signalling between Schwann cells a nd axons governing myelination. Here we show that a fragment distal to the Oct-6 gene, containing two DNase I-hypersensitive sites, acts as the Oct-6 Schwann cell-specific enhancer (SCE). The SCE is sufficient to drive spatia lly and temporally correct expression, during both normal peripheral nerve development and regeneration. We further demonstrate that a tagged version of Oct-6, driven by the SCE, rescues the peripheral nerve phenotype of Oct- 6-deficient mice. Thus, our isolation and characterization of the Oct-6 SCE provides the first description of a cis-acting genetic element that respon ds to converging signalling pathways to drive myelination in the peripheral nervous system.