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

被引:45
作者
Ghazvini, M
Mandemakers, W
Jaegle, M
Piirsoo, M
Driegen, S
Koutsourakis, M
Smit, X
Grosveld, F
Meijer, D
机构
[1] Erasmus Univ, Dept Cell Biol & Genet, NL-3000 DR Rotterdam, Netherlands
[2] Erasmus Univ, Dept Neurosci, NL-3000 DR Rotterdam, Netherlands
[3] Erasmus Univ, Dept Reconstruct Surg, NL-3000 DR Rotterdam, Netherlands
关键词
enhancer; glia; myelin; Oct-6; POU domain;
D O I
10.1093/emboj/cdf475
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 (DeltaSCE 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.
引用
收藏
页码:4612 / 4620
页数:9
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