Vimentin regulates peripheral nerve myelination

Daniela Triolo, Giorgia Dina, Carla Taveggia, Ilaria Vaccari, Emanuela Porrello, Cristina Rivellini, Teuta Domi, Rosa la Marca, Federica Cerri, Alessandra Bolino, Angelo Quattrini, Stefano Carlo Previtali

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Abstract

Myelination is a complex process that requires coordinated Schwann cell-axon interactions during development and regeneration. Positive and negative regulators of myelination have been recently described, and can belong either to Schwann cells or neurons. Vimentin is a fibrous component present in both Schwann cell and neuron cytoskeleton, the expression of which is timely and spatially regulated during development and regeneration. We now report that vimentin negatively regulates myelination, as loss of vimentin results in peripheral nerve hypermyelination, owing to increased myelin thickness in vivo, in transgenic mice and in vitro in a myelinating co-culture system. We also show that this is due to a neuron-autonomous increase in the levels of axonal neuregulin 1 (NRG1) type III. Accordingly, genetic reduction of NRG1 type III in vimentin-null mice rescues hypermyelination. Finally, we demonstrate that vimentin acts synergistically with TACE, a negative regulator of NRG1 type III activity, as shown by hypermyelination of double Vim/Tace heterozygous mice. Our results reveal a novel role for the intermediate filament vimentin in myelination, and indicate vimentin as a regulator of NRG1 type III function.

Original languageEnglish
Pages (from-to)1359-1367
Number of pages9
JournalDevelopment
Volume139
Issue number7
DOIs
Publication statusPublished - Apr 1 2012

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Keywords

  • Cytoskeleton
  • Mouse
  • Myelination
  • Neuregulin 1 type III
  • TACE

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology

Cite this

Triolo, D., Dina, G., Taveggia, C., Vaccari, I., Porrello, E., Rivellini, C., Domi, T., la Marca, R., Cerri, F., Bolino, A., Quattrini, A., & Previtali, S. C. (2012). Vimentin regulates peripheral nerve myelination. Development, 139(7), 1359-1367. https://doi.org/10.1242/dev.072371