RT Journal Article
SR Electronic
T1 Neuregulin 1–erbB Signaling Is Necessary for Normal Myelination and Sensory Function
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 3079
OP 3086
DO 10.1523/JNEUROSCI.3785-05.2006
VO 26
IS 12
A1 Suzhen Chen
A1 Miguel Omar Velardez
A1 Xavier Warot
A1 Zhao-Xue Yu
A1 Shyra J. Miller
A1 Didier Cros
A1 Gabriel Corfas
YR 2006
UL http://www.jneurosci.org/content/26/12/3079.abstract
AB To investigate the role of erbB signaling in the interactions between peripheral axons and myelinating Schwann cells, we generated transgenic mice expressing a dominant-negative erbB receptor in these glial cells. Mutant mice have delayed onset of myelination, thinner myelin, shorter internodal length, and smaller axonal caliber in adulthood. Consistent with the morphological defects, transgenic mice also have slower nerve conduction velocity and defects in their responses to mechanical stimulation. Molecular analysis indicates that erbB signaling may contribute to myelin formation by regulating transcription of myelin genes. Analysis of sciatic nerves showed a reduction in the levels of expression of myelin genes in mutant mice. In vitro assays revealed that neuregulin-1 (NRG1) induces expression of myelin protein zero (P0). Furthermore, we found that the effects of NRG1 on P0 expression depend on the NRG1 isoform used. When NRG1 is presented to Schwann cells in the context of cell–cell contact, type III but not type I NRG1 regulates P0 gene expression. These results suggest that disruption of the NRG1–erbB signaling pathway could contribute to the pathogenesis of peripheral neuropathies with hypomyelination and neuropathic pain.