The class IIIPOU domain protein Brn-1 can fully replace the related Oct-6 during Schwann cell development and myelination
The class IIIPOU domain protein Brn-1 can fully replace the related Oct-6 during Schwann cell development and myelination
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DOI：
10.1128/mcb.25.5.1821-1829.2005
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发表时间：
2005-03-01
影响因子：
5.3
通讯作者：
Wegner, M
中科院分区：
文献类型：
--
作者：
Friedrich, RP;Schlierf, B;Wegner, M
为了进行分化，施万细胞依赖于 III 类 POU 结构域转录因子 Oct-6，当施万细胞与轴突建立一对一关系但尚未开始髓鞘化时，该因子会短暂表达。 Oct-6 的缺失会导致髓鞘形成阶段的短暂停滞和髓鞘形成的延迟。尽管密切相关的 POU 结构域蛋白 Brn-2 在雪旺细胞中与 Oct-6 共表达，但其丢失仅产生轻微的后果。相反，两种 POU 结构域蛋白的联合丢失会显着增加髓鞘形成延迟，从而提出相关 POU 结构域蛋白的活性如何相互比较的问题。在这里，我们用 III 类 POU 结构域蛋白 Brn-1 的表达取代了小鼠中 Oct-6 的表达。尽管这种蛋白在雪旺细胞中通常不表达，但 Brn-1 能够完全替代 Oct-6。 Brn-1 有效诱导 Krox-20 表达，这是髓鞘形成的先决条件。在仅携带 Brn-1 而不是 Oct-6 等位基因的小鼠中，髓鞘形成的开始和程度也与野生型小鼠没有区别。与 Oct-6 类似，Brn-1 在髓鞘形成的后期下调其自身表达。因此，III类POU结构域蛋白在雪旺细胞发育过程中可以完全相互替代。
For differentiation, Schwann cells rely on the class III POU domain transcription factor Oct-6, which is expressed transiently when Schwann cells have established a one-to-one relation with axons but have not yet started to myelinate. Loss of Oct-6 leads to a transient arrest in this promyelinating stage and a delay in myelination. Although the closely related POU domain protein Brn-2 is coexpressed with Oct-6 in Schwann cells, its loss has only mild consequences. Combined loss of both POU domain proteins, in contrast, dramatically increases the myelination delay, raising the question of how related POU domain proteins compare to each other in their activities. Here, we have replaced Oct-6 expression in the mouse with expression of the class III POU domain protein Brn-1. Although this protein is not normally expressed in Schwann cells, Brn-1 was capable of fully replacing Oct-6. Brn-1 efficiently induced Krox-20 expression as a prerequisite for myelination. Onset and extent of myelination were also indistinguishable from that of the wild type in mice that carried only Brn-1 instead of Oct-6 alleles. Similar to Oct-6, Brn-1 down-regulated its own expression at later stages of myelination. Thus, class III POU domain proteins can fully replace each other in Schwann cell development.