Ghazvini Merhnaz, Mandemakers Wim, Jaegle Martine, Piirsoo Marko, Driegen Siska, Koutsourakis Manousos, Smit Xsander, Grosveld Frank, Meijer Dies
Department of Cell Biology and Genetics, Erasmus University Rotterdam, PO Box 1738, 3000DR Rotterdam, The Netherlands.
EMBO J. 2002 Sep 2;21(17):4612-20. 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 (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.
虽然POU结构域转录因子Oct-6在发育中的周围神经中所起的重要作用已得到充分证实,但由于新生Oct-6突变动物的高死亡率,对其在神经发育和再生中的确切作用的研究受到了阻碍。在本研究中,我们通过缺失Oct-6基因座中的雪旺细胞特异性增强子元件(SCE),生成了一个雪旺细胞特异性的Oct-6等位基因。对该等位基因纯合的小鼠(deltaSCE等位基因)的分析表明,雪旺细胞中Oct-6的限速水平依赖于SCE,并且该元件对其他细胞类型中Oct-6的调控没有贡献。我们证明了Oct-6在神经发育以及再生神经过程中具有雪旺细胞自主功能。此外,我们还表明,Krox-20是Oct-6在雪旺细胞中的一个重要调控靶点,在这些小鼠中,它通过一种不依赖Oct-6的机制被激活,但其动力学延迟。