Document Detail

Notch controls embryonic Schwann cell differentiation, postnatal myelination and adult plasticity.
MedLine Citation:
PMID:  19525946     Owner:  NLM     Status:  MEDLINE    
Notch signaling is central to vertebrate development, and analysis of Notch has provided important insights into pathogenetic mechanisms in the CNS and many other tissues. However, surprisingly little is known about the role of Notch in the development and pathology of Schwann cells and peripheral nerves. Using transgenic mice and cell cultures, we found that Notch has complex and extensive regulatory functions in Schwann cells. Notch promoted the generation of Schwann cells from Schwann cell precursors and regulated the size of the Schwann cell pool by controlling proliferation. Notch inhibited myelination, establishing that myelination is subject to negative transcriptional regulation that opposes forward drives such as Krox20. Notably, in the adult, Notch dysregulation resulted in demyelination; this finding identifies a signaling pathway that induces myelin breakdown in vivo. These findings are relevant for understanding the molecular mechanisms that control Schwann cell plasticity and underlie nerve pathology, including demyelinating neuropathies and tumorigenesis.
Ashwin Woodhoo; Maria B Duran Alonso; Anna Droggiti; Mark Turmaine; Maurizio D'Antonio; David B Parkinson; Daniel K Wilton; Raya Al-Shawi; Paul Simons; Jie Shen; Francois Guillemot; Freddy Radtke; Dies Meijer; M Laura Feltri; Lawrence Wrabetz; Rhona Mirsky; Kristján R Jessen
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-06-14
Journal Detail:
Title:  Nature neuroscience     Volume:  12     ISSN:  1546-1726     ISO Abbreviation:  Nat. Neurosci.     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-06-25     Completed Date:  2009-07-07     Revised Date:  2014-09-20    
Medline Journal Info:
Nlm Unique ID:  9809671     Medline TA:  Nat Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  839-47     Citation Subset:  IM    
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MeSH Terms
Cell Differentiation / physiology*
Cell Proliferation
Cells, Cultured
Coculture Techniques
Demyelinating Diseases / metabolism
Early Growth Response Protein 2 / genetics,  metabolism
Glycoproteins / metabolism
Immunoglobulin J Recombination Signal Sequence-Binding Protein / metabolism
Mice, Transgenic
Myelin Sheath / physiology*
Nerve Tissue Proteins / metabolism
Neural Crest / cytology,  physiology
Neuregulin-1 / metabolism
Peripheral Nerve Injuries
Peripheral Nerves / embryology,  growth & development
Receptor, erbB-2 / metabolism
Receptors, Notch / metabolism*
Schwann Cells / cytology,  physiology*
Signal Transduction*
Time Factors
Grant Support
G0601943//Medical Research Council; MC_U117570528//Medical Research Council; R01 NS042818/NS/NINDS NIH HHS; R01 NS042818-07/NS/NINDS NIH HHS; R01 NS045630/NS/NINDS NIH HHS; R01 NS045630-06/NS/NINDS NIH HHS; R01 NS045630-07/NS/NINDS NIH HHS; R01 NS045630-08/NS/NINDS NIH HHS; R01 NS045630-09/NS/NINDS NIH HHS; R01 NS055256/NS/NINDS NIH HHS; //Wellcome Trust
Reg. No./Substance:
0/Early Growth Response Protein 2; 0/Erbb2 protein, rat; 0/Glycoproteins; 0/Immunoglobulin J Recombination Signal Sequence-Binding Protein; 0/Nerve Tissue Proteins; 0/Neuregulin-1; 0/Nrg1 protein, mouse; 0/Nrg1 protein, rat; 0/Rbpj protein, mouse; 0/Receptors, Notch; EC protein, mouse; EC, erbB-2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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