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The Journal of Neuroscience, February 15, 2006, 26(7):2124-2131; doi:10.1523/JNEUROSCI.4594-05.2006

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Development/Plasticity/Repair
ErbB2 Signaling in Schwann Cells Is Mostly Dispensable for Maintenance of Myelinated Peripheral Nerves and Proliferation of Adult Schwann Cells after Injury

Suzana Atanasoski,¹ Steven S. Scherer,² Erich Sirkowski,² Dino Leone,¹ Alistair N. Garratt,³ Carmen Birchmeier,³ and Ueli Suter¹

¹Institute of Cell Biology, Department of Biology, ETH Zurich, CH-8093 Zurich, Switzerland, ²Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6146, and ³Max-Delbrück-Centrum for Molecular Medicine, 13092 Berlin, Germany

Correspondence should be addressed to Dr. Ueli Suter, Institute of Cell Biology, ETH-Hönggerberg, CH-8093 Zurich, Switzerland. Email: usuter{at}cell.biol.ethz.ch

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.

Key words: peripheral nerves; Schwann cells; Wallerian degeneration; receptor tyrosine kinases; Cre-loxP system; proliferation

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Received Aug. 7, 2005; revised Jan. 4, 2006; accepted Jan. 11, 2006.

Correspondence should be addressed to Dr. Ueli Suter, Institute of Cell Biology, ETH-Hönggerberg, CH-8093 Zurich, Switzerland. Email: usuter{at}cell.biol.ethz.ch

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