NRG1 type I dependent autoparacrine stimulation of Schwann cells in onion bulbs 
of peripheral neuropathies

Fledrich, Robert; Akkermann, Dagmar; Schütza, Vlad; Abdelaal, Tamer A. M.; Hermes, Doris; Schäffner, Erik; Soto Bernardini, Maria Clara; Götze, Tilmann; Klink, Axel; Kusch, Kathrin; Krueger, Martin; Kungl, Theresa; Frydrychowicz, Clara; Möbius, Wiebke; Brück, Wolfgang; Mueller, Wolf C.; Bechmann, Ingo; Sereda, Michael Werner; Schwab, Markus H.; Nave, Klaus-Armin; Stassart, Ruth M.

doi:10.1038/s41467-019-09886-4

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NRG1 type I dependent autoparacrine stimulation of Schwann cells in onion bulbs of peripheral neuropathies

MPS-Authors

/persons/resource/persons182152

Fledrich, Robert
Molecular and translational neurology, Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons232140

Akkermann, Dagmar
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons224786

Schütza, Vlad
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182057

Abdelaal, Tamer A. M.
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons224792

Hermes, Doris
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons232141

Schäffner, Erik
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons207307

Soto Bernardini, Maria Clara
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182462

Götze, Tilmann
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182248

Klink, Axel
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182268

Kusch, Kathrin
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182265

Kungl, Theresa
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182306

Möbius, Wiebke
Electron microscopy, Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182406

Sereda, Michael Werner
Molecular and translational neurology, Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182402

Schwab, Markus H.
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182320

Nave, Klaus-Armin
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182427

Stassart, Ruth M.
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

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Citation

Fledrich, R., Akkermann, D., Schütza, V., Abdelaal, T. A. M., Hermes, D., Schäffner, E., et al. (2019). NRG1 type I dependent autoparacrine stimulation of Schwann cells in onion bulbs of peripheral neuropathies. Nature Communications, 10: 1467. doi:10.1038/s41467-019-09886-4.

Cite as: https://hdl.handle.net/21.11116/0000-0003-5571-E

Abstract

In contrast to acute peripheral nerve injury, the molecular response of Schwann cells in chronic neuropathies remains poorly understood. Onion bulb structures are a pathological hallmark of demyelinating neuropathies, but the nature of these formations is unknown. Here, we show that Schwann cells induce the expression of Neuregulin-1 type I (NRG1-I), a paracrine growth factor, in various chronic demyelinating diseases. Genetic disruption of Schwann cell-derived NRG1 signalling in a mouse model of Charcot-Marie-Tooth Disease 1A (CMT1A), suppresses hypermyelination and the formation of onion bulbs. Transgenic overexpression of NRG1-I in Schwann cells on a wildtype background is sufficient to mediate an interaction between Schwann cells via an ErbB2 receptor-MEK/ERK signaling axis, which causes onion bulb formations and results in a peripheral neuropathy reminiscent of CMT1A. We suggest that diseased Schwann cells mount a regeneration program that is beneficial in acute nerve injury, but that overstimulation of Schwann cells in chronic neuropathies is detrimental.