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 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.
Mandemakers
W
W
Department of Cell Biology and Genetics and Department of Plastic Surgery, Erasmus University Rotterdam, PO Box 1738, 3000 DR Rotterdam, The Netherlands.
Zwart
R
R
Jaegle
M
M
Walbeehm
E
E
Visser
P
P
Grosveld
F
F
Meijer
D
D
D000818:Animals; D001369:Axons / Q000378:metabolism; D001483:Base Sequence; D002450:Cell Communication; D002454:Cell Differentiation; D017124:Conserved Sequence; D000242:Cyclic AMP / Q000494:pharmacology; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D016296:Mutagenesis; D009186:Myelin Sheath / Q000378:metabolism*; D009416:Nerve Regeneration / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D050816:Octamer Transcription Factor-6; D010525:Peripheral Nerves / Q000196:embryology*; D012583:Schwann Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics*
D018840:HSP70 Heat-Shock Proteins; C490786:HSPA1A protein, human; C494178:POU3F1 protein, human; C494180:Pou3f1 protein, mouse; D014157:Transcription Factors; D050816:Octamer Transcription Factor-6; D000242:Cyclic AMP