Format

Send to

Choose Destination
Nat Commun. 2018 Mar 2;9(1):899. doi: 10.1038/s41467-018-03336-3.

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

Author information

1
Institut für Biochemie, Emil-Fischer-Zentrum, Friedrich-Alexander-Universität Erlangen-Nürnberg, D-91054, Erlangen, Germany.
2
Institute of Neuropathology, University Hospital Münster, D-48149, Münster, Germany.
3
Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, D-48149, Münster, Germany.
4
Department of Molecular Neurology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, D-91054, Erlangen, Germany.
5
Institute of Neuropathology, University Hospital Münster, D-48149, Münster, Germany. Tanja.Kuhlmann@ukmuenster.de.
6
Institut für Biochemie, Emil-Fischer-Zentrum, Friedrich-Alexander-Universität Erlangen-Nürnberg, D-91054, Erlangen, Germany. michael.wegner@fau.de.

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.

PMID:
29500351
PMCID:
PMC5834605
DOI:
10.1038/s41467-018-03336-3
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center