ACTL6a knockout peripheral nerve RNA seq at postnatal day 3

Cells need to integrate chemical and physical signals into transcriptional programs. In the peripheral nerves, axonal caliber selection by specialized Schwann cells, is critical for developmental myelination. However, only mechanisms through which Schwann cells sense chemical signals are well characterized. We identify ACtin-Like protein 6a (ACTL6a), a component of the SWI/SNF chromatin remodeling complex, as critical for axonal caliber recognition and developmental myelination. ACTL6a is expressed in the developing nerve and, when activated by contact with axons or nanofibers of specific caliber, it promotes the eviction of repressive histone marks thereby enhancing the transcriptional program of myelination. Mutant mice with Schwann cells lacking ACTL6a display aberrant recognition of axonal caliber, resulting in defective radial sorting and lower levels of transcripts regulating myelination of developing nerves. We suggest that developing peripheral nerves require an ACTL6a-dependent integration of physical and chemical signals in Schwann cells to release of repressive histone modifications and promote myelination. compare RNA seq results from the postnatal day 3 sciatic nerve of wild type and CnpcreActl6a mouse mutant细胞需将化学与物理信号整合至转录程序中。在周围神经系统中，特化施万细胞（Schwann cells）对轴突直径的选择，对于发育性髓鞘形成至关重要。然而，目前仅对施万细胞感知化学信号的机制有较为充分的研究与阐释。本研究鉴定出肌动蛋白样蛋白6a（ACtin-Like protein 6a，ACTL6a）——SWI/SNF染色质重塑复合物的组分之一，其对于轴突直径识别与发育性髓鞘形成具有关键作用。ACTL6a在发育中的神经组织中表达；当与特定直径的轴突或纳米纤维接触而被激活时，它可促进抑制性组蛋白标记的移除，从而增强髓鞘形成相关的转录程序。缺失ACTL6a的施万细胞突变小鼠会表现出轴突直径识别异常，进而引发发育神经的径向分选缺陷，以及髓鞘形成调控转录本表达水平降低的表型。本研究提示，发育中的周围神经系统需要施万细胞中依赖ACTL6a的物理与化学信号整合过程，以解除抑制性组蛋白修饰并促进髓鞘形成。对比野生型与CnpcreActl6a突变小鼠出生后第3天坐骨神经的RNA测序（RNA-seq）结果