Nrg1/ErbB signaling networks in Schwann cell development and myelination

Jason Newbern, Carmen Birchmeier

Research output: Contribution to journalReview article

133 Scopus citations

Abstract

Neuregulin-1 (Nrg1) provides a key axonal signal that regulates Schwann cell proliferation, migration and myelination through binding to ErbB2/3 receptors. The analysis of a number of genetic models has unmasked fundamental mechanisms underlying the specificity of the Nrg1/ErbB signaling axis. Differential expression of Nrg1 isoforms, Nrg1 processing, and ErbB receptor localization and trafficking represent important regulatory themes in the control of Nrg1/ErbB function. Nrg1 binding to ErbB2/3 receptors results in the activation of intracellular signal transduction pathways that initiate changes in Schwann cell behavior. Here, we review data that has defined the role of key Nrg1/ErbB signaling components like Shp2, ERK1/2, FAK, Rac1/Cdc42 and calcineurin in development of the Schwann cell lineage in vivo. Many of these regulators receive converging signals from other cues that are provided by Notch, integrin or G-protein coupled receptors. Signaling by multiple extracellular factors may act as key modifiers and allow Schwann cells at different developmental stages to respond in distinct manners to the Nrg1/ErbB signal.

Original languageEnglish (US)
Pages (from-to)922-928
Number of pages7
JournalSeminars in Cell and Developmental Biology
Volume21
Issue number9
DOIs
StatePublished - Dec 2010
Externally publishedYes

Keywords

  • Erbin
  • Erk
  • Myelination
  • Neuregulin
  • Shp2

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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