Document Detail

Dgcr8 controls neural crest cells survival in cardiovascular development.
MedLine Citation:
PMID:  22138056     Owner:  NLM     Status:  MEDLINE    
DiGeorge syndrome (DGS), characterized genetically by a deletion within chromosome 22q11.2, is associated with a constellation of congenital heart defects. DiGeorge critical region 8 (Dgcr8), a gene that maps to the common deletion region of DGS, encodes a double stranded RNA-binding protein that is essential for miRNA biogenesis. To address the potential contribution of Dgcr8 insufficiency to cardiovascular development, we have inactivated Dgcr8 in cardiac neural crest cells (cNCCs). Dgcr8 mutants displayed a wide spectrum of malformations, including persistent truncus arteriosus (PTA) and ventricular septal defect (VSD). Interestingly, Dgcr8-null cNCCs that properly migrated into the cardiac outflow tract (OFT), proliferate normally and differentiate into vascular smooth muscle cells. However, loss of Dgcr8 causes a significant portion of the cNCCs to undergo apoptosis, causing a decrease in the pool of progenitors required for OFT remodeling. Our data uncover a new role of Dgcr8 in cardiovascular morphogenesis, plausibly as part of transmission mechanism for FGF-dependent survival cue for migrating cNCCs.
Elik Chapnik; Vered Sasson; Robert Blelloch; Eran Hornstein
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-11-23
Journal Detail:
Title:  Developmental biology     Volume:  362     ISSN:  1095-564X     ISO Abbreviation:  Dev. Biol.     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-01-10     Completed Date:  2012-02-28     Revised Date:  2014-09-27    
Medline Journal Info:
Nlm Unique ID:  0372762     Medline TA:  Dev Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  50-6     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
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MeSH Terms
Cardiovascular System / cytology,  embryology*
Cell Survival / physiology*
Crosses, Genetic
Gene Knockout Techniques
Histological Techniques
In Situ Hybridization
Mice, Transgenic
MicroRNAs / biosynthesis*
Morphogenesis / physiology*
Neural Crest / cytology*
Proteins / genetics,  metabolism*
Signal Transduction / genetics,  physiology*
Reg. No./Substance:
0/Dgcr8 protein, mouse; 0/MicroRNAs; 0/Proteins; EC

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