A cell type-specific allele of the POU gene Oct-6 reveals Schwann cell autonomous function in nerve development and regeneration

• Published in: The EMBO journal 2002-09, Vol.21 (17), p.4612-4620
• Main Authors: Ghazvini, Merhnaz, Mandemakers, Wim, Jaegle, Martine, Piirsoo, Marko, Driegen, Siska, Koutsourakis, Manousos, Smit, Xsander, Grosveld, Frank, Meijer, Dies
• Format: Article
• Language: English
• Subjects: Alleles; Animals; Cell Lineage; Chimera; Crosses, Genetic; DNA-Binding Proteins - metabolism; Early Growth Response Protein 2; EMBO09; EMBO27; enhancer; Enhancer Elements, Genetic - genetics; Female; Gene Targeting; glia; Male; Mice; myelin; Myelin Sheath - physiology; Nerve Regeneration - physiology; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - physiology; Oct-6; Octamer Transcription Factor-6; Organ Specificity; Peripheral Nerves - anatomy & histology; Peripheral Nerves - growth & development; POU domain; Schwann Cells - physiology; Sequence Deletion; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription Factors - physiology
• ISSN: 0261-4189; 1460-2075; 1460-2075
• DOI: 10.1093/emboj/cdf475

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 (Δ SCE 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.