Cells elaborate transcriptional programs in response to external signals. In the peripheral nerves, Schwann cells (SC) sort axons of given caliber and start the process of wrapping their membrane around them. We identify Actin- Like protein 6a (ACTL6a), part of SWI/SNF chromatin remodeling complex, as critical for the integration of axonal caliber recognition with the transcriptional program of myelination. Nuclear levels of ACTL6A in SC are increased by contact with large caliber axons or nanofibers, and result in the eviction of repressive histone marks to facilitate myelination. Without Actl6a the SC are unable to coordinate caliber recognition and myelin production. Peripheral nerves in knock out mice display defective radial sorting, hypo-myelination of large caliber axons and redundant myelin around small caliber axons, resulting in a clinical motor phenotype. Overall, this suggests that ACTL6A is a key component of the machinery integrating external signals for proper myelination of the peripheral nerve.

细胞根据外部信号精心设计转录程序。在周围神经中，施万细胞（SC）对给定口径的轴突进行分类，并开始将膜包裹在轴突周围。我们发现肌动蛋白样蛋白 6a (ACTL6a) 是 SWI/SNF 染色质重塑复合物的一部分，对于轴突口径识别与髓鞘形成转录程序的整合至关重要。 SC 中 ACTL6A 的核水平通过与大口径轴突或纳米纤维接触而增加，并导致抑制性组蛋白标记被驱逐以促进髓鞘形成。如果没有Actl6a， SC 就无法协调口径识别和髓磷脂生成。基因敲除小鼠的周围神经表现出径向排序缺陷、大口径轴突髓鞘形成不足和小口径轴突周围髓鞘过剩，导致临床运动表型。总的来说，这表明 ACTL6A 是整合外部信号以实现周围神经正确髓鞘化的机制的关键组成部分。