Recent studies have elucidated the crucial role for microRNAs in peripheral nerve myelination by ablating components of the microRNA synthesis machinery. Few studies have focused on the role of individual microRNAs. To fill this gap, we focused this study on miR-138, which was shown to be drastically reduced in Dicer1 and Dgcr8 knockout mice with hypomyelinating phenotypes and to potentially target the negative regulators of Schwann cell differentiation. Here, we show that of two miR-138 encoding loci, mir-138-1 is the predominant locus transcribed in Schwann cells. mir-138-1 is transcriptionally upregulated during myelination and downregulated upon nerve injury. EGR2 is required for mir-138-1 transcription during development, and both SOX10 and EGR2 bind to an active enhancer near the mir-138-1 locus. Based on expression analyses, we hypothesized that miR-138 facilitates the transition between undifferentiated Schwann cells and myelinating Schwann cells. However, in conditional knockouts, we could not detect significant changes in Schwann cell proliferation, cell cycle exit, or myelination. Overall, our results demonstrate that miR-138 is an Egr2-dependent microRNA but is dispensable for Schwann cell myelination.
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