Yy1 as a molecular link between neuregulin and transcriptional modulation of peripheral myelination

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

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Author(s)

  • Ye He
  • Jeffrey Dupree
  • Ambika Tewari
  • Carmen Melendez-Vasquez
  • John Svaren
  • Patrizia Casaccia

Detail(s)

Original languageEnglish
Pages (from-to)1472-1482
Journal / PublicationNature Neuroscience
Volume13
Issue number12
Publication statusPublished - Dec 2010
Externally publishedYes

Abstract

Fast axonal conduction depends on myelin, which is formed by Schwann cells in the PNS. We found that the transcription factor Yin Yang 1 (YY1) is crucial for peripheral myelination. Conditional ablation of Yy1 in the Schwann cell lineage resulted in severe hypomyelination, which occurred independently of altered Schwann cell proliferation or apoptosis. In Yy1 mutant mice, Schwann cells established a 1:1 relationship with axons but were unable to myelinate them. The Schwann cells expressed low levels of myelin proteins and of Egr2 (also called Krox20), which is an important regulator of peripheral myelination. In vitro, Schwann cells that lacked Yy1 did not upregulate Egr2 in response to neuregulin1 and did not express myelin protein zero. This phenotype was rescued by overexpression of Egr2. In addition, neuregulin-induced phosphorylation of YY1 was required for transcriptional activation of Egr2. Thus, YY1 emerges as an important activator of peripheral myelination that links neuregulin signaling with Egr2 expression. © 2010 Nature America, Inc. All rights reserved.

Citation Format(s)

Yy1 as a molecular link between neuregulin and transcriptional modulation of peripheral myelination. / He, Ye; Kim, Jin Young; Dupree, Jeffrey; Tewari, Ambika; Melendez-Vasquez, Carmen; Svaren, John; Casaccia, Patrizia.

In: Nature Neuroscience, Vol. 13, No. 12, 12.2010, p. 1472-1482.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal