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

机译:POU基因Oct-6的一种细胞类型特异性等位基因揭示了雪旺细胞在神经发育和再生中的自主功能

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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 (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.
机译:尽管已经很好地确定了POU域转录因子Oct-6在发育中的周围神经中的重要作用,但由于其新生的Oct-6突变动物的高死亡率,阻碍了其在神经发育和再生中的确切作用的研究。在这项研究中,我们通过删除Oct-6位点中的Schwann细胞特异性增强子(SCE)产生了Schwann细胞特异性Oct-6等位基因。对该等位基因(ΔSCE等位基因)纯合子的小鼠分析显示,雪旺细胞中Oct-6的限速水平取决于SCE,并且该元素在其他细胞类型中无助于Oct-6调节。我们证明了神经发育以及再生神经中Oct-6的雪旺细胞自主功能。此外,我们显示Krox-20是Schwann细胞中Oct-6的重要调控靶标,通过这些小鼠的Oct-6独立机制被激活,具有动力学延迟。

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