A cell type-specific allele of the POU gene Oct-6 reveals Schwann cell autonomous function in nerve development and regeneration.
EMBO Journal , Volume 21 - Issue 17 p. 4612- 4620
While an important role for the POU domain transcription factor Oct-6 in the developing peripheral nerve has been well established, studies into its exact role in nerve development and regeneration have been hampered by the high mortality rate of newborn Oct-6 mutant animals. In this study we have generated a Schwann cell-specific Oct-6 allele through deletion of the Schwann cell-specific enhancer element (SCE) in the Oct-6 locus. Analysis of mice homozygous for this allele (ΔSCE allele) reveals that rate-limiting levels of Oct-6 in Schwann cells are dependent on the SCE and that this element does not contribute to Oct-6 regulation in other cell types. We demonstrate a Schwann cell autonomous function for Oct-6 during nerve development as well as in regenerating nerve. Additionally, we show that Krox-20, an important regulatory target of Oct-6 in Schwann cells, is activated, with delayed kinetics, through an Oct-6-independent mechanism in these mice.
|*Enhancer Elements, Genetic/genetics, Alleles, Animals, Cell Lineage, Chimera, Crosses, Genetic, DNA-Binding Proteins/metabolism, Early Growth Response Protein 2, Female, Gene Targeting, Male, Mice, Myelin Sheath/physiology, Nerve Regeneration/*physiology, Nerve Tissue Proteins/genetics/physiology, Octamer Transcription Factor-6, Organ Specificity, Peripheral Nerves/anatomy & histology/*growth & development, Schwann Cells/*physiology, Sequence Deletion, Transcription Factors/genetics/metabolism/*physiology|
|Free full text in PubMed Central|
|Organisation||Erasmus MC: University Medical Center Rotterdam|
Ghazvini, M, Mandemakers, W.J, Jaegle, M.M, Piirsoo, M, Koutsourakis, M, Smit, X, … Driegen, M.J.F. (2002). A cell type-specific allele of the POU gene Oct-6 reveals Schwann cell autonomous function in nerve development and regeneration. EMBO Journal, 21(17), 4612–4620. doi:10.1093/emboj/cdf475