Neuregulin 1-erbB signaling is necessary for normal myelination and sensory func

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J Neurosci. 2006 Mar 22;26(12):3079-86.

Neuregulin 1-erbB signaling is necessary for normal myelination and

sensory function.

Chen S, Velardez MO, Warot X, Yu ZX, SJ, Cros D, Corfas G.

Division of Neuroscience, Children's Hospital Boston, Harvard Medical

School, Boston, Massachusetts 02115, USA.

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.