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A distal Schwann cell‐specific enhancer mediates axonal regulation of the Oct‐6 transcription factor during peripheral nerve development and regeneration
Author(s) -
Mandemakers Wim,
Zwart Ronald,
Jaegle Martine,
Walbeehm Erik,
Visser Pim,
Grosveld Frank,
Meijer Dies
Publication year - 2000
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/19.12.2992
Subject(s) - schwann cell , enhancer , transcription factor , regeneration (biology) , biology , peripheral nervous system , microbiology and biotechnology , neuroscience , gene , central nervous system , genetics
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.