Zeb2 is essential for Schwann cell differentiation, myelination and nerve repair

Quintes S, Brinkmann BG, Ebert M, Fröb F, Kungl T, Arlt FA, Tarabykin V, Huylebroeck D, Meijer D, Suter U, Wegner M, Sereda MW, Nave KA (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Nature Neuroscience Nature Publishing Group

Book Volume: 19

Pages Range: 1050-9

Journal Issue: 8

DOI: 10.1038/nn.4321

Abstract

Schwann cell development and peripheral nerve myelination require the serial expression of transcriptional activators, such as Sox10, Oct6 (also called Scip or Pou3f1) and Krox20 (also called Egr2). Here we show that transcriptional repression, mediated by the zinc-finger protein Zeb2 (also known as Sip1), is essential for differentiation and myelination. Mice lacking Zeb2 in Schwann cells develop a severe peripheral neuropathy, caused by failure of axonal sorting and virtual absence of myelin membranes. Zeb2-deficient Schwann cells continuously express repressors of lineage progression. Moreover, genes for negative regulators of maturation such as Sox2 and Ednrb emerge as Zeb2 target genes, supporting its function as an 'inhibitor of inhibitors' in myelination control. When Zeb2 is deleted in adult mice, Schwann cells readily dedifferentiate following peripheral nerve injury and become repair cells. However, nerve regeneration and remyelination are both perturbed, demonstrating that Zeb2, although undetectable in adult Schwann cells, has a latent function throughout life.

Authors with CRIS profile

Franziska Thiele Lehrstuhl für Biochemie und Pathobiochemie Michael Wegner Lehrstuhl für Biochemie und Pathobiochemie

Involved external institutions

Max-Planck-Institut für Experimentelle Medizin DE Germany (DE) Charité - Universitätsmedizin Berlin DE Germany (DE) Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven BE Belgium (BE) University of Edinburgh GB United Kingdom (GB) Eidgenössische Technische Hochschule Zürich (ETHZ) / Swiss Federal Institute of Technology in Zurich CH Switzerland (CH)

How to cite

APA:

Quintes, S., Brinkmann, B.G., Ebert, M., Fröb, F., Kungl, T., Arlt, F.A.,... Nave, K.-A. (2016). Zeb2 is essential for Schwann cell differentiation, myelination and nerve repair. Nature Neuroscience, 19(8), 1050-9. https://dx.doi.org/10.1038/nn.4321

MLA:

Quintes, Susanne, et al. "Zeb2 is essential for Schwann cell differentiation, myelination and nerve repair." Nature Neuroscience 19.8 (2016): 1050-9.

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