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Kao SC, Wu H, Xie J, Chang CP, Ranish JA, Graef IA, Crabtree GR. Calcineurin/NFAT signaling is required for neuregulin-regulated Schwann cell differentiation. Science. 2009 Jan 30 ; 323(5914):651-4. Pubmed Abstract

Comments on News and Primary Papers


Primary Papers: Calcineurin/NFAT signaling is required for neuregulin-regulated Schwann cell differentiation.

Comment by:  Markus Schwab
Submitted 13 February 2009
Posted 13 February 2009

Understanding signaling pathways that control myelination is essential to develop therapies for human diseases, which are associated with de- or dysmyelination, such as schizophrenia. In a recent paper in Science, the laboratories of Isabella Graef and Gerald Crabtree at Stanford University have now identified the Ca+-dependent phosphatase salcineurin and downstream transcription factor NFATc3 as an important signaling pathway for Schwann cell (SC) myelination in vivo. In mouse mutants lacking calcineurin, SC differentiation and early steps of myelination are defective. They also offer an exciting link to the neuregulin1-ErbB signaling pathway, which is essential for peripheral myelination. They demonstrate that in vitro NRG1 stimulates phospholipaseγ-dependent Ca+ influx into SC precursors and calcineurin-dependent dephosphorylation of NFATc3, which activates transcription of Krox-20, an important coordinator of myelin protein expression. Since NRG1 and calcineurin variants have been associated with schizophrenia and are expressed in various brain regions, e.g., the cerebral cortex, it will be important to address a functional link beween these factors also in the CNS.

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