Document Detail

TACE/ADAM17 Is Essential for Oligodendrocyte Development and CNS Myelination.
MedLine Citation:
PMID:  25186737     Owner:  NLM     Status:  In-Data-Review    
Several studies have elucidated the significance of a disintegrin and metalloproteinase proteins (ADAMs) in PNS myelination, but there is no evidence if they also play a role in oligodendrogenesis and CNS myelination. Our study identifies ADAM17, also called tumor necrosis factor-α converting enzyme (TACE), as a novel key modulator of oligodendrocyte (OL) development and CNS myelination. Genetic deletion of TACE in oligodendrocyte progenitor cells (OPs) induces premature cell cycle exit and reduces OL cell survival during postnatal myelination of the subcortical white matter (SCWM). These cellular and molecular changes lead to deficits in SCWM myelination and motor behavior. Mechanistically, TACE regulates oligodendrogenesis by modulating the shedding of EGFR ligands TGFα and HB-EGF and, consequently, EGFR signaling activation in OL lineage cells. Constitutive TACE depletion in OPs in vivo leads to similar alterations in CNS myelination and motor behavior as to what is observed in the EGFR hypofunctional mouse line EgfrWa2. EGFR overexpression in TACE-deficient OPs restores OL survival and development. Our study reveals an essential function of TACE in oligodendrogenesis, and demonstrates how this molecule modulates EGFR signaling activation to regulate postnatal CNS myelination.
Javier Palazuelos; Howard C Crawford; Michael Klingener; Bingru Sun; Jason Karelis; Elaine W Raines; Adan Aguirre
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of neuroscience : the official journal of the Society for Neuroscience     Volume:  34     ISSN:  1529-2401     ISO Abbreviation:  J. Neurosci.     Publication Date:  2014 Sep 
Date Detail:
Created Date:  2014-09-04     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  11884-96     Citation Subset:  IM    
Copyright Information:
Copyright © 2014 the authors 0270-6474/14/3411884-13$15.00/0.
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