TY - JOUR
T1 - Egr2-dependent microRNA-138 is dispensable for peripheral nerve myelination
AU - Lin, Hsin Pin
AU - Oksuz, Idil
AU - Svaren, John
AU - Awatramani, Rajeshwar
N1 - Funding Information:
This work was supported by National Institutes of Health Grants 1R01NS071081-01(R.A.) and R01 NS100510-01A1 (J.S. and R.A.). Part of this work was performed at the Center for Advanced Microscopy and the Mouse Histology and Phenotyping Laboratory of Northwestern University generously supported by NCI CCSG P30 CA060553 awarded to the Robert H Lurie Comprehensive Cancer Center. We thank Mr. Lennell Reynolds Jr. and Dr. Wensheng Liu for technical assistance.
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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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U2 - 10.1038/s41598-018-22010-8
DO - 10.1038/s41598-018-22010-8
M3 - Article
C2 - 29491350
AN - SCOPUS:85042942892
SN - 2045-2322
VL - 8
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 3817
ER -