Document Detail

Zebrafish Mef2ca and Mef2cb are essential for both first and second heart field cardiomyocyte differentiation.
MedLine Citation:
PMID:  22750409     Owner:  NLM     Status:  MEDLINE    
Mef2 transcription factors have been strongly linked with early heart development. D-mef2 is required for heart formation in Drosophila, but whether Mef2 is essential for vertebrate cardiomyocyte (CM) differentiation is unclear. In mice, although Mef2c is expressed in all CMs, targeted deletion of Mef2c causes lethal loss of second heart field (SHF) derivatives and failure of cardiac looping, but first heart field CMs can differentiate. Here we examine Mef2 function in early heart development in zebrafish. Two Mef2c genes exist in zebrafish, mef2ca and mef2cb. Both are expressed similarly in the bilateral heart fields but mef2cb is strongly expressed in the heart poles at the primitive heart tube stage. By using fish mutants for mef2ca and mef2cb and antisense morpholinos to knock down either or both Mef2cs, we show that Mef2ca and Mef2cb have essential but redundant roles in myocardial differentiation. Loss of both Mef2ca and Mef2cb function does not interfere with early cardiogenic markers such as nkx2.5, gata4 and hand2 but results in a dramatic loss of expression of sarcomeric genes and myocardial markers such as bmp4, nppa, smyd1b and late nkx2.5 mRNA. Rare residual CMs observed in mef2ca;mef2cb double mutants are ablated by a morpholino capable of knocking down other Mef2s. Mef2cb over-expression activates bmp4 within the cardiogenic region, but no ectopic CMs are formed. Surprisingly, anterior mesoderm and other tissues become skeletal muscle. Mef2ca single mutants have delayed heart development, but form an apparently normal heart. Mef2cb single mutants have a functional heart and are viable adults. Our results show that the key role of Mef2c in myocardial differentiation is conserved throughout the vertebrate heart.
Yaniv Hinits; Luyuan Pan; Charline Walker; John Dowd; Cecilia B Moens; Simon M Hughes
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-06-28
Journal Detail:
Title:  Developmental biology     Volume:  369     ISSN:  1095-564X     ISO Abbreviation:  Dev. Biol.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-08-20     Completed Date:  2012-10-29     Revised Date:  2014-04-08    
Medline Journal Info:
Nlm Unique ID:  0372762     Medline TA:  Dev Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  199-210     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
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MeSH Terms
Animals, Genetically Modified
Base Sequence
Cell Differentiation / genetics
DNA Primers / genetics
Gene Expression Regulation, Developmental
Heart / embryology
Muscle Development / genetics
Muscle Proteins / genetics*
Myocardium / cytology
Myocytes, Cardiac / cytology*,  metabolism*
Myogenic Regulatory Factors / genetics*
RNA, Messenger / genetics,  metabolism
Zebrafish / embryology*,  genetics*
Zebrafish Proteins / genetics*
Grant Support
DE13834/DE/NIDCR NIH HHS; G1001029//Medical Research Council; HD22486/HD/NICHD NIH HHS; P01 HD022486/HD/NICHD NIH HHS; P30 CA015704/CA/NCI NIH HHS; R01 DE013834/DE/NIDCR NIH HHS; R01 HG002995/HG/NHGRI NIH HHS; R01HG002995/HG/NHGRI NIH HHS; //British Heart Foundation; //Medical Research Council
Reg. No./Substance:
0/DNA Primers; 0/Mef2 protein, zebrafish; 0/Mef2cb protein, zebrafish; 0/Muscle Proteins; 0/Myogenic Regulatory Factors; 0/RNA, Messenger; 0/Zebrafish Proteins

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