ErbB2 signaling in Schwann cells is mostly dispensable for maintenance of myelinated peripheral nerves and proliferation of adult Schwann cells after injury

Neuregulin/erbB signaling is critically required for survival and proliferation of Schwann cells as well as for establishing correct myelin thickness of peripheral nerves during development. In this study, we investigated whether erbB2 signaling in Schwann cells is also essential for the maintenance of myelinated peripheral nerves and for Schwann cell proliferation and survival after nerve injury. To this end, we used inducible Cre-loxP technology using a PLP-CreERT2 allele to ablate erbB2 in adult Schwann cells. ErbB2 expression was markedly reduced after induction of erbB2 gene disruption with no apparent effect on the maintenance of already established myelinated peripheral nerves. In contrast to development, Schwann cell proliferation and survival were not impaired in mutant animals after nerve injury, despite reduced levels of MAPK-P (phosphorylated mitogen-activated protein kinase) and cyclin D1. ErbB1 and erbB4 do not compensate for the loss of erbB2. We conclude that adult Schwann cells do not require major neuregulin signaling through erbB2 for proliferation and survival after nerve injury, in contrast to development and in cell culture

Control of peripheral nerve myelination by the beta-secretase BACE1

Although BACE1 (beta-site amyloid precursor protein-cleaving enzyme 1) is essential for the generation of amyloid-b peptide in Alzheimer's disease, its physiological function is unclear. We found that very high levels of BACE1 were expressed at time points when peripheral nerves become myelinated. Deficiency of BACE1 resulted in the accumulation of unprocessed neuregulin 1 (NRG1), an axonally expressed factor required for glial cell development and myelination. BACE1-/- mice displayed hypomyelination of peripheral nerves and aberrant axonal segregation of small-diameter afferent fibers, very similar to that seen in mice with mutations in type III NRG1 or Schwann cell-specific ErbB2 knockouts. Thus, BACE1 is required for myelination and correct bundling of axons by Schwann cells, probably through processing of type III NRG1.status: publishe