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

Matthias Weider, Laura Julia Starost, Katharina Groll, Melanie Küspert, Elisabeth Sock, Miriam Wedel, Franziska Fröb, Christian Schmitt, Tina Baroti, Anna C. Hartwig, Simone Hillgärtner, Sandra Piefke, Tanja Fadler, Marc Ehrlich, Corinna Ehlert, Martin Stehling, Stefanie Albrecht, Ammar Jabali, Hans R. Schöler, Jürgen Winkler, Tanja Kuhlmann () and Michael Wegner ()
Additional contact information
Matthias Weider: Friedrich-Alexander-Universität Erlangen-Nürnberg
Laura Julia Starost: University Hospital Münster
Katharina Groll: University Hospital Münster
Melanie Küspert: Friedrich-Alexander-Universität Erlangen-Nürnberg
Elisabeth Sock: Friedrich-Alexander-Universität Erlangen-Nürnberg
Miriam Wedel: Friedrich-Alexander-Universität Erlangen-Nürnberg
Franziska Fröb: Friedrich-Alexander-Universität Erlangen-Nürnberg
Christian Schmitt: Friedrich-Alexander-Universität Erlangen-Nürnberg
Tina Baroti: Friedrich-Alexander-Universität Erlangen-Nürnberg
Anna C. Hartwig: Friedrich-Alexander-Universität Erlangen-Nürnberg
Simone Hillgärtner: Friedrich-Alexander-Universität Erlangen-Nürnberg
Sandra Piefke: Friedrich-Alexander-Universität Erlangen-Nürnberg
Tanja Fadler: Friedrich-Alexander-Universität Erlangen-Nürnberg
Marc Ehrlich: University Hospital Münster
Corinna Ehlert: University Hospital Münster
Martin Stehling: Max Planck Institute for Molecular Biomedicine
Stefanie Albrecht: University Hospital Münster
Ammar Jabali: University Hospital Münster
Hans R. Schöler: Max Planck Institute for Molecular Biomedicine
Jürgen Winkler: Friedrich-Alexander-Universität Erlangen-Nürnberg
Tanja Kuhlmann: University Hospital Münster
Michael Wegner: Friedrich-Alexander-Universität Erlangen-Nürnberg

Nature Communications, 2018, vol. 9, issue 1, 1-16

Abstract: 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.

Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03336-3

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DOI: 10.1038/s41467-018-03336-3

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