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.
Institute of Cell Biology, Department of Biology, ETH Zurich, CH-8093 Zurich, Switzerland.
Suzana
S
Atanasoski
Steven S
SS
Scherer
Erich
E
Sirkowski
Dino
D
Leone
Alistair N
AN
Garratt
Carmen
C
Birchmeier
Ueli
U
Suter
D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002455:Cell Division; D017931:DNA Primers; D018734:Genes, erbB-2 / Q000502:physiology*; D005838:Genotype; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009186:Myelin Sheath / Q000473:pathology / Q000502:physiology*; D020890:Neuregulin-1 / Q000502:physiology; D012583:Schwann Cells / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D015398:Signal Transduction
D002352:Carrier Proteins; D017931:DNA Primers; C498804:Erbb2ip protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D020890:Neuregulin-1