The Microprocessor–Dicer Axis Prevents Inappropriate Activity of Injury Response Genes in Developing and Adult Schwann Cells

Myelination is fundamental for proper function of the nervous system. In peripheral nerves, Schwann cells (SCs) myelinate axons and the miRNA pathway was shown to be required for developmental myelination and myelin maintenance. However, the stages of myelination the miRNA pathway acts on are not fully understood. Here, we addressed the requirement of Dgcr8, Drosha and Dicer in developing and adult SCs using mouse mutants. We found the microprocessor components Dgcr8 and Drosha to be critical for radial sorting and correct SC numbers upon myelination. Transcriptome analysis revealed a requirement of the microprocessor in preventing inappropriate accumulation and de novo expression of injury response genes, which are predicted to targets of stage-specifically enriched miRNAs. Consistently, Dgcr8 and Dicer are required for proper maintenance of the myelinated SC fate. We conclude that the microprocessor-Dicer axis is crucial for preventing inappropriate activity of injury response genes in developing and adult SCs.