Document Detail


The PAF1 complex differentially regulates cardiomyocyte specification.
MedLine Citation:
PMID:  21338598     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The specification of an appropriate number of cardiomyocytes from the lateral plate mesoderm requires a careful balance of both positive and negative regulatory signals. To identify new regulators of cardiac specification, we performed a phenotype-driven ENU mutagenesis forward genetic screen in zebrafish. In our genetic screen we identified a zebrafish ctr9 mutant with a dramatic reduction in myocardial cell number as well as later defects in primitive heart tube elongation and atrioventricular boundary patterning. Ctr9, together with Paf1, Cdc73, Rtf1 and Leo1, constitute the RNA polymerase II associated protein complex, PAF1. We demonstrate that the PAF1 complex (PAF1C) is structurally conserved among zebrafish and other metazoans and that loss of any one of the components of the PAF1C results in abnormal development of the atrioventricular boundary of the heart. However, Ctr9, Cdc73, Paf1 and Rtf1, but not Leo1, are required for the specification of an appropriate number of cardiomyocytes and elongation of the heart tube. Interestingly, loss of Rtf1 function produced the most severe defects, resulting in a nearly complete absence of cardiac precursors. Based on gene expression analyses and transplantation studies, we found that the PAF1C regulates the developmental potential of the lateral plate mesoderm and is required cell autonomously for the specification of cardiac precursors. Our findings demonstrate critical but differential requirements for PAF1C components in zebrafish cardiac specification and heart morphogenesis.
Authors:
Adam D Langenbacher; Catherine T Nguyen; Ann M Cavanaugh; Jie Huang; Fei Lu; Jau-Nian Chen
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2011-02-19
Journal Detail:
Title:  Developmental biology     Volume:  353     ISSN:  1095-564X     ISO Abbreviation:  Dev. Biol.     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-04-12     Completed Date:  2011-06-08     Revised Date:  2014-09-18    
Medline Journal Info:
Nlm Unique ID:  0372762     Medline TA:  Dev Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  19-28     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Body Patterning*
Cell Movement
Heart / embryology*
Morphogenesis
Myocytes, Cardiac / cytology*
Nuclear Proteins / physiology
Stem Cells / physiology
Transcription Factors / physiology*
Zebrafish / embryology*
Zebrafish Proteins / physiology*
Grant Support
ID/Acronym/Agency:
HL081700/HL/NHLBI NIH HHS; R01 HL081700/HL/NHLBI NIH HHS; R01 HL081700-04/HL/NHLBI NIH HHS; R01 HL096980/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Leo1 protein, zebrafish; 0/Nuclear Proteins; 0/Rtf1 protein, zebrafish; 0/Transcription Factors; 0/Zebrafish Proteins
Comments/Corrections

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