Document Detail


The cyclin-dependent kinase inhibitor p57kip2 is a negative regulator of Schwann cell differentiation and in vitro myelination.
MedLine Citation:
PMID:  18550808     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The p57kip2 gene encodes a member of the cyclin-dependent kinase inhibitor family, proteins known to block G(1)/S transition during the mammalian cell cycle. We observed that expression of p57kip2 in Schwann cells of the developing and injured adult peripheral nervous system is dynamically regulated. Using gene knockdown by means of vector-based RNA interference in cultured primary Schwann cells we found that reduced levels of p57kip2 lead to cell cycle exit, actin filament stabilization, altered cell morphology and growth, and down-regulation of promyelinating markers as well as induction of myelin genes and proteins. In addition, we could demonstrate that in vitro myelination is enhanced by p57kip2-suppressed Schwann cells. Using microarray technology we found that these cellular reactions are specific to lowered p57kip2 expression levels and detected a shift of the transcriptional expression program toward the pattern known from Schwann cells in developing peripheral nerves. Because in the absence of axons primary Schwann cells normally do not display differentiation-associated reactions, we conclude that we have identified a mechanism and an important intrinsic negative regulator of myelinating glia differentiation.
Authors:
André Heinen; David Kremer; Peter Göttle; Fabian Kruse; Birgit Hasse; Helmar Lehmann; Hans Peter Hartung; Patrick Küry
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-06-11
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  105     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-06-25     Completed Date:  2008-08-19     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  8748-53     Citation Subset:  IM    
Affiliation:
Department of Neurology, Heinrich Heine University, Moorenstrasse 5, D-40225 Düsseldorf, Germany.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Cycle
Cell Differentiation
Cells, Cultured
Cyclin-Dependent Kinase Inhibitor p57 / genetics,  metabolism*
Down-Regulation
Myelin Sheath / metabolism*
RNA Interference
Rats
Schwann Cells / cytology,  metabolism*
Transfection
Chemical
Reg. No./Substance:
0/Cyclin-Dependent Kinase Inhibitor p57
Comments/Corrections

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