Institut für Biochemie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Fahrstrasse 17, 91054, Erlangen, Germany.
Institut für Humananatomie und Embryologie, Universität Regensburg, Regensburg, Germany.
Sci Rep. 2022 Feb 16;12(1):2651. doi: 10.1038/s41598-022-06588-8.
Myelin sheath formation in the peripheral nervous system and the ensuing saltatory conduction rely on differentiated Schwann cells. We have previously shown that transition of Schwann cells from an immature into a differentiated state requires Brg1 that serves as the central energy generating subunit in two related SWI/SNF-type chromatin remodelers, the BAF and the PBAF complex. Here we used conditional deletion of Pbrm1 to selectively interfere with the PBAF complex in Schwann cells. Despite efficient loss of Pbrm1 early during lineage progression, we failed to detect any substantial alterations in the number, proliferation or survival of immature Schwann cells as well as in their rate and timing of terminal differentiation. As a consequence, postnatal myelin formation in peripheral nerves appeared normal. There were no inflammatory alterations in the nerve or other signs of a peripheral neuropathy. We conclude from our study that Pbrm1 and very likely the PBAF complex are dispensable for proper Schwann cell development and that Schwann cell defects previously observed upon Brg1 deletion are mostly attributable to altered or absent function of the BAF complex.
周围神经系统髓鞘的形成和随后的跳跃传导依赖于分化的雪旺细胞。我们之前已经表明,雪旺细胞从未成熟状态向分化状态的转变需要 Brg1,Brg1 是两种相关的 SWI/SNF 型染色质重塑体(BAF 和 PBAF 复合物)中的中央能量产生亚基。在这里,我们使用条件性敲除 Pbrm1 来选择性地干扰雪旺细胞中的 PBAF 复合物。尽管在谱系进展的早期有效缺失了 Pbrm1,但我们未能检测到未成熟雪旺细胞的数量、增殖或存活,以及它们的终末分化的速度和时间有任何实质性的改变。因此,周围神经中的出生后髓鞘形成似乎正常。神经中没有炎症改变或其他周围神经病变的迹象。我们从研究中得出结论,Pbrm1 非常可能还有 PBAF 复合物对于雪旺细胞的正常发育是可有可无的,并且之前在 Brg1 缺失时观察到的雪旺细胞缺陷主要归因于 BAF 复合物的改变或缺失功能。