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

Weider, Matthias ; Starost, Laura Julia ; Groll, Katharina ; Küspert, Melanie ; Sock, Elisabeth ; Wedel, Miriam ; Fröb, Franziska ; Schmitt, Christian ; Baroti, Tina ; Hartwig, Anna C ; Hillgärtner, Simone ; Piefke, Sandra ; Fadler, Tanja ; Ehrlich, Marc ; Ehlert, Corinna ; Stehling, Martin ; Albrecht, Stefanie ; Jabali, Ammar ; Schöler, Hans R ; Winkler, Jürgen ; Kuhlmann, Tanja ; Wegner, Michael

Nature communications, 2018-03, Vol.9 (1), p.899-16, Article 899 [Periódico revisado por pares]

England: Nature Publishing Group

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Título:
Nfat/calcineurin signaling promotes oligodendrocyte differentiation and myelination by transcription factor network tuning
Autor: Weider, Matthias ; Starost, Laura Julia ; Groll, Katharina ; Küspert, Melanie ; Sock, Elisabeth ; Wedel, Miriam ; Fröb, Franziska ; Schmitt, Christian ; Baroti, Tina ; Hartwig, Anna C ; Hillgärtner, Simone ; Piefke, Sandra ; Fadler, Tanja ; Ehrlich, Marc ; Ehlert, Corinna ; Stehling, Martin ; Albrecht, Stefanie ; Jabali, Ammar ; Schöler, Hans R ; Winkler, Jürgen ; Kuhlmann, Tanja ; Wegner, Michael
Assuntos: Activation ; Animals ; Calcineurin ; Calcineurin - metabolism ; Calcium ; Calcium signalling ; Cell Differentiation ; Central nervous system ; Conserved Sequence ; Demyelination ; Differentiation ; Evolution, Molecular ; Gene Expression Regulation ; Homeodomain Proteins - metabolism ; Humans ; Lesions ; Mice ; Multiple sclerosis ; Myelin ; Myelin Sheath - metabolism ; Myelination ; NF-AT protein ; NFATC Transcription Factors - metabolism ; Nkx2.2 protein ; Olig2 protein ; Oligodendrocyte Transcription Factor 2 - metabolism ; Oligodendrocytes ; Oligodendroglia - cytology ; Oligodendroglia - metabolism ; Proteins ; Rats ; Regulators ; Rodents ; Signal Transduction ; Sox10 protein ; SOXE Transcription Factors - metabolism ; Transcription factors ; Transcription Factors - metabolism
É parte de: Nature communications, 2018-03, Vol.9 (1), p.899-16, Article 899
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Descrição: 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.
Editor: England: Nature Publishing Group
Idioma: Inglês

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

England: Nature Publishing Group

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