Microprocessor complex subunit digeorge syndrome critical region gene 8 (DGCR8) is required for Schwann cell myelination and myelin maintenance

Hsin Pin Lin, Idil Oksuz, Edward Hurley, Lawrence Wrabetz, Rajeshwar Awatramani*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

We investigated the role of a key component of the Microprocessor complex, DGCR8, in the regulation of myelin formation and maintenance.Wefound that conditionally ablatingDgcr8in 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 Dgcr8cKO 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 injuryrelated 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.

Original languageEnglish (US)
Pages (from-to)24294-24307
Number of pages14
JournalJournal of Biological Chemistry
Volume290
Issue number40
DOIs
StatePublished - Oct 2 2015

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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