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

AUTOR(ES)

Mandemakers, Wim

FONTE

Oxford University Press

RESUMO

The POU domain transcription factor Oct-6 is a major regulator of Schwann cell differentiation and myelination. During nerve development and regeneration, expression of Oct-6 is under the control of axonal signals. Identification of the cis-acting elements necessary for Oct-6 gene regulation is an important step in deciphering the complex signalling between Schwann cells and 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 spatially 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 responds to converging signalling pathways to drive myelination in the peripheral nervous system.

Documentos Relacionados

• A cell type-specific allele of the POU gene Oct-6 reveals Schwann cell autonomous function in nerve development and regeneration
• Prolactin upstream factor I mediates cell-specific transcription.
• The POU proteins Brn-2 and Oct-6 share important functions in Schwann cell development
• A cell-specific factor represses stimulation of transcription in vitro by transcriptional enhancer factor 1.
• The Class III POU Domain Protein Brn-1 Can Fully Replace the Related Oct-6 during Schwann Cell Development and Myelination