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

First Author  Kao SC Year  2009
Journal  Science Volume  323
Issue  5914 Pages  651-4
PubMed ID  19179536 Mgi Jnum  J:144171
Mgi Id  MGI:3830391 Doi  10.1126/science.1166562
Citation  Kao SC, et al. (2009) Calcineurin/NFAT signaling is required for neuregulin-regulated Schwann cell differentiation. Science 323(5914):651-4
abstractText  Schwann cells develop from multipotent neural crest cells and form myelin sheaths around axons that allow rapid transmission of action potentials. Neuregulin signaling through the ErbB receptor regulates Schwann cell development; however, the downstream pathways are not fully defined. We find that mice lacking calcineurin B1 in the neural crest have defects in Schwann cell differentiation and myelination. Neuregulin addition to Schwann cell precursors initiates an increase in cytoplasmic Ca2+, which activates calcineurin and the downstream transcription factors NFATc3 and c4. Purification of NFAT protein complexes shows that Sox10 is an NFAT nuclear partner and synergizes with NFATc4 to activate Krox20, which regulates genes necessary for myelination. Our studies demonstrate that calcineurin and NFAT are essential for neuregulin and ErbB signaling, neural crest diversification, and differentiation of Schwann cells.
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