Nfat/calcineurin signaling promotes oligodendrocyte differentiation and myelination by transcription factor network tuning.

Weider M, Starost LJ, Groll K, Küspert M, Sock E, Wedel M, Fröb F, Schmitt C, Baroti T, Hartwig A, Hillgärtner S, Piefke S, Fadler T, Ehrlich M, Ehlert C, Stehling M, Albrecht S, Jabali A, Schoeler HR, Winkler J, Kuhlmann T, Wegner M (2018)

Publication Type: Journal article, Original article

Publication year: 2018

Journal

Nature Communications Nature Publishing Group: Nature Communications

Publisher: Nature Publishing Group

Book Volume: 9

Pages Range: 899

Journal Issue: 9

DOI: 10.1038/s41467-018-03336-3

Abstract

Oligodendrocytes produce myelin for rapid transmission and saltatory conduction of action potentials in the vertebrate central nervous system. Activation of the myelination program requires several transcription factors including Sox10, Olig2, and Nkx2.2. Functional interactions among them are poorly understood and important components of the regulatory network are still unknown. Here, we identify Nfat proteins as Sox10 targets and regulators of oligodendroglial differentiation in rodents and humans. Overall levels and nuclear fraction increase during differentiation. Inhibition of Nfat activity impedes oligodendrocyte differentiation in vitro and in vivo. On a molecular level, Nfat proteins cooperate with Sox10 to relieve reciprocal repression of Olig2 and Nkx2.2 as precondition for oligodendroglial differentiation and myelination. As Nfat activity depends on calcium-dependent activation of calcineurin signaling, regulatory network and oligodendroglial differentiation become sensitive to calcium signals. NFAT proteins are also detected in human oligodendrocytes, downregulated in active multiple sclerosis lesions and thus likely relevant in demyelinating disease.

Authors with CRIS profile

Matthias Weider Lehrstuhl für Biochemie und Pathobiochemie Melanie Küspert Lehrstuhl für Biochemie und Pathobiochemie Elisabeth Sock Lehrstuhl für Biochemie und Pathobiochemie Miriam Wedel Lehrstuhl für Biochemie und Pathobiochemie Franziska Thiele Lehrstuhl für Biochemie und Pathobiochemie Christian Schmitt Lehrstuhl für Biochemie und Pathobiochemie Tina Baroti Lehrstuhl für Biochemie und Pathobiochemie Anna Hartwig Lehrstuhl für Biochemie und Pathobiochemie Simone Hillgärtner Lehrstuhl für Biochemie und Pathobiochemie Sandra Piefke Lehrstuhl für Biochemie und Pathobiochemie Tanja Fadler Lehrstuhl für Biochemie und Pathobiochemie Jürgen Winkler Professur für Molekulare Neurologie Michael Wegner Lehrstuhl für Biochemie und Pathobiochemie

Involved external institutions

Max-Planck-Institut für molekulare Biomedizin / Max Planck Institute for Molecular Biomedicine DE Germany (DE) Universitätsklinikum Münster DE Germany (DE)

How to cite

APA:

Weider, M., Starost, L.J., Groll, K., Küspert, M., Sock, E., Wedel, M.,... Wegner, M. (2018). Nfat/calcineurin signaling promotes oligodendrocyte differentiation and myelination by transcription factor network tuning. Nature Communications, 9(9), 899. https://doi.org/10.1038/s41467-018-03336-3

MLA:

Weider, Matthias, et al. "Nfat/calcineurin signaling promotes oligodendrocyte differentiation and myelination by transcription factor network tuning." Nature Communications 9.9 (2018): 899.

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