Document Detail


Calcineurin/NFAT signaling is required for neuregulin-regulated Schwann cell differentiation.
MedLine Citation:
PMID:  19179536     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Shih-Chu Kao; Hai Wu; Jianming Xie; Ching-Pin Chang; Jeffrey A Ranish; Isabella A Graef; Gerald R Crabtree
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Science (New York, N.Y.)     Volume:  323     ISSN:  1095-9203     ISO Abbreviation:  Science     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2009-01-30     Completed Date:  2009-02-19     Revised Date:  2010-12-17    
Medline Journal Info:
Nlm Unique ID:  0404511     Medline TA:  Science     Country:  United States    
Other Details:
Languages:  eng     Pagination:  651-4     Citation Subset:  IM    
Affiliation:
Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Calcineurin / metabolism*
Calcium / metabolism
Cell Differentiation
Cell Line
Coculture Techniques
Early Growth Response Protein 2 / metabolism
Ganglia, Spinal / cytology
Mice
Myelin Sheath / physiology
NFATC Transcription Factors / metabolism*
Neural Crest / cytology,  metabolism
Neuregulins / metabolism*
Phosphorylation
Receptor, erbB-2 / metabolism
Receptor, erbB-3
SOXE Transcription Factors / metabolism
Schwann Cells / cytology*,  metabolism*
Signal Transduction*
Grant Support
ID/Acronym/Agency:
AI60037/AI/NIAID NIH HHS; HD55391/HD/NICHD NIH HHS; NS046789/NS/NINDS NIH HHS; R01 AI060037-01/AI/NIAID NIH HHS; R01 AI060037-02/AI/NIAID NIH HHS; R01 AI060037-03/AI/NIAID NIH HHS; R01 AI060037-04/AI/NIAID NIH HHS; R01 AI060037-05/AI/NIAID NIH HHS; R01 HD055391-04/HD/NICHD NIH HHS; R01 NS046789-01/NS/NINDS NIH HHS; R01 NS046789-02/NS/NINDS NIH HHS; R01 NS046789-03/NS/NINDS NIH HHS; R01 NS046789-04/NS/NINDS NIH HHS; R01 NS046789-05/NS/NINDS NIH HHS; R21 NS061702-01/NS/NINDS NIH HHS; //Howard Hughes Medical Institute
Chemical
Reg. No./Substance:
0/Early Growth Response Protein 2; 0/Egr2 protein, mouse; 0/NFATC Transcription Factors; 0/Neuregulins; 0/Nfatc3 protein, mouse; 0/Nfatc4 protein, mouse; 0/SOXE Transcription Factors; 0/Sox10 protein, mouse; 7440-70-2/Calcium; EC 2.7.10.1/Erbb2 protein, mouse; EC 2.7.10.1/Receptor, erbB-2; EC 2.7.10.1/Receptor, erbB-3; EC 3.1.3.16/Calcineurin
Comments/Corrections

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