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- W2275559239 abstract "We investigated the role of a key component of the Microprocessor complex, DGCR8, in the regulation of myelin formation and maintenance. We found that conditionally ablating Dgcr8 in Schwann cells (SCs) during development results in an arrest of SC differentiation. Dgcr8 conditional knock-out (cKO) SCs fail to form 1:1 relationships with axons or, having achieved this, fail to form myelin sheaths. The expression of genes normally found in immature SCs, such as sex-determining region Y-box 2 (Sox2), is increased in Dgcr8 cKO SCs, whereas the expression of myelin-related genes, including the master regulatory transcription factor early growth response 2 (Egr2), is decreased. Additionally, expression of a novel gene expression program involving sonic hedgehog (Shh), activated de novo in injured nerves, is elevated in Dgcr8 cKOs but not in Egr2 null mice, a model of SC differentiation arrest, suggesting that the injury-related gene expression program in Dgcr8 cKOs cannot be attributed to differentiation arrest. Inducible ablation of Dgcr8 in adult SCs results in gene expression changes similar to those found in cKOs, including an increase in the expression of Sox2 and Shh. Analyses of these nerves mainly reveal normal myelin thickness and axon size distribution but some dedifferentiated SCs and increased macrophage infiltration. Together our data suggest that Dgcr8 is responsible for modulation of gene expression programs underlying myelin formation and maintenance as well as suppression of an injury-related gene expression program." @default.
- W2275559239 created "2016-06-24" @default.
- W2275559239 creator A5013348651 @default.
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- W2275559239 creator A5082378596 @default.
- W2275559239 creator A5084082896 @default.
- W2275559239 date "2015-10-01" @default.
- W2275559239 modified "2023-09-29" @default.
- W2275559239 title "Microprocessor Complex Subunit DiGeorge Syndrome Critical Region Gene 8 (Dgcr8) Is Required for Schwann Cell Myelination and Myelin Maintenance" @default.
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- W2275559239 doi "https://doi.org/10.1074/jbc.m115.636407" @default.