Document Detail


Epicardially derived fibroblasts preferentially contribute to the parietal leaflets of the atrioventricular valves in the murine heart.
MedLine Citation:
PMID:  22546693     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The importance of the epicardium for myocardial and valvuloseptal development has been well established; perturbation of epicardial development results in cardiac abnormalities, including thinning of the ventricular myocardial wall and malformations of the atrioventricular valvuloseptal complex. To determine the spatiotemporal contribution of epicardially derived cells to the developing fibroblast population in the heart, we have used a mWt1/IRES/GFP-Cre mouse to trace the fate of EPDCs from embryonic day (ED)10 until birth. EPDCs begin to populate the compact ventricular myocardium around ED12. The migration of epicardially derived fibroblasts toward the interface between compact and trabecular myocardium is completed around ED14. Remarkably, epicardially derived fibroblasts do not migrate into the trabecular myocardium until after ED17. Migration of EPDCs into the atrioventricular cushion mesenchyme commences around ED12. As development progresses, the number of EPDCs increases significantly, specifically in the leaflets which derive from the lateral atrioventricular cushions. In these developing leaflets the epicardially derived fibroblasts eventually largely replace the endocardially derived cells. Importantly, the contribution of EPDCs to the leaflets derived from the major AV cushions is very limited. The differential contribution of EPDCs to the various leaflets of the atrioventricular valves provides a new paradigm in valve development and could lead to new insights into the pathogenesis of abnormalities that preferentially affect individual components of this region of the heart. The notion that there is a significant difference in the contribution of epicardially and endocardially derived cells to the individual leaflets of the atrioventricular valves has also important pragmatic consequences for the use of endocardial and epicardial cre-mouse models in studies of heart development.
Authors:
Andy Wessels; Maurice J B van den Hoff; Richard F Adamo; Aimee L Phelps; Marie M Lockhart; Kimberly Sauls; Laura E Briggs; Russell A Norris; Bram van Wijk; Jose M Perez-Pomares; Robert W Dettman; John B E Burch
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-04-24
Journal Detail:
Title:  Developmental biology     Volume:  366     ISSN:  1095-564X     ISO Abbreviation:  Dev. Biol.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-05-21     Completed Date:  2013-07-05     Revised Date:  2014-04-09    
Medline Journal Info:
Nlm Unique ID:  0372762     Medline TA:  Dev Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  111-24     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Embryonic Development
Fibroblasts / cytology*
Heart / embryology*
Heart Valves / cytology,  embryology*
Heart Ventricles / cytology,  embryology
Mice
Organogenesis
Pericardium / cytology*
Grant Support
ID/Acronym/Agency:
3P20RR016434-10S1/RR/NCRR NIH HHS; 5T32 HL007260/HL/NHLBI NIH HHS; 5T32-GM008716-12/GM/NIGMS NIH HHS; C06RR015455/RR/NCRR NIH HHS; C06RR018823/RR/NCRR NIH HHS; P20 RR016434/RR/NCRR NIH HHS; R01 HL033756/HL/NHLBI NIH HHS; R01 HL055373/HL/NHLBI NIH HHS; R01 HL084285/HL/NHLBI NIH HHS; R01 HL084285/HL/NHLBI NIH HHS; R01-HL055373/HL/NHLBI NIH HHS; T32 GM008716/GM/NIGMS NIH HHS; T32 HL007260/HL/NHLBI NIH HHS
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