The miRNA biogenesis pathway prevents inappropriate expression of injury response genes in developing and adult Schwann cells. Issue 12 (8th October 2018) - Gökbuget, Deniz
Abstract : Proper function of the nervous system depends on myelination. In peripheral nerves, Schwann cells (SCs) myelinate axons and the miRNA biogenesis pathway is required for developmental myelination and myelin maintenance. However, regulatory roles of this pathway at different stages of myelination are only partially understood. We addressed the requirement of the core miRNA biogenesis pathway components Dgcr8, Drosha, and Dicer in developing and adult SCs using mouse mutants with a comparative genetics and transcriptomics approach. We found that the microprocessor components Dgcr8 and Drosha are crucial for axonal radial sorting and to establish correct SC numbers upon myelination. Transcriptome analyses revealed a requirement of the microprocessor to prevent aberrantly increased expression of injury‐response genes. Those genes are predicted targets of abundant miRNAs in sciatic nerves (SNs) during developmental myelination. In agreement, Dgcr8 and Dicer are required for proper maintenance of the myelinated SC state, where abundant miRNAs in adult SNs are predicted to target injury‐response genes. We conclude that the miRNA biogenesis pathway in SCs is crucial for preventing inappropriate activity of injury‐response genes in developing and adult SCs. Main Points: Dgcr8 and Drosha drive radial sorting of axons and inhibit injury‐response gene expression in developing peripheral nerves. Abundant miRNAs in nerves are predicted to target injury‐response genes. Dgcr8 and Dicer are required for myelin maintenance.