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Semin Cell Dev Biol. 2010 Dec;21(9):922-8. doi: 10.1016/j.semcdb.2010.08.008. Epub 2010 Sep 9.

Nrg1/ErbB signaling networks in Schwann cell development and myelination.

Author information

1
Neuroscience Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA. jason newbern@med.unc.edu

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.

PMID:
20832498
PMCID:
PMC2991617
DOI:
10.1016/j.semcdb.2010.08.008
[Indexed for MEDLINE]
Free PMC Article

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