Nrg1/ErbB signaling networks in Schwann cell development and myelination.
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.
Newbern
Jason
J
Neuroscience Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA. jason newbern@med.unc.edu
Birchmeier
Carmen
C
D000818:Animals; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D009186:Myelin Sheath / Q000378:metabolism*; D020890:Neuregulin-1 / Q000378:metabolism*; D055495:Neurogenesis; D012583:Schwann Cells / Q000378:metabolism*; D015398:Signal Transduction
D020890:Neuregulin-1; C512478:EGFR protein, human; D066246:ErbB Receptors