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PLoS Genet. 2019 Feb 5;15(2):e1007962. doi: 10.1371/journal.pgen.1007962. eCollection 2019 Feb.

Nr2f-dependent allocation of ventricular cardiomyocyte and pharyngeal muscle progenitors.

Author information

1
Division of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States of America.
2
Molecular and Developmental Biology Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH, United States of America.
3
Master's Program in Genetics, Department of Life Sciences, Université Paris Diderot, Paris, France.
4
Molecular Genetics and Human Genetics Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH, United States of America.
5
Molecular and Developmental Biology Master's Program, University of Cincinnati College of Medicine, Cincinnati, OH, United States of America.
6
Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, CA, United States of America.
7
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States of America.

Abstract

Multiple syndromes share congenital heart and craniofacial muscle defects, indicating there is an intimate relationship between the adjacent cardiac and pharyngeal muscle (PM) progenitor fields. However, mechanisms that direct antagonistic lineage decisions of the cardiac and PM progenitors within the anterior mesoderm of vertebrates are not understood. Here, we identify that retinoic acid (RA) signaling directly promotes the expression of the transcription factor Nr2f1a within the anterior lateral plate mesoderm. Using zebrafish nr2f1a and nr2f2 mutants, we find that Nr2f1a and Nr2f2 have redundant requirements restricting ventricular cardiomyocyte (CM) number and promoting development of the posterior PMs. Cre-mediated genetic lineage tracing in nr2f1a; nr2f2 double mutants reveals that tcf21+ progenitor cells, which can give rise to ventricular CMs and PM, more frequently become ventricular CMs potentially at the expense of posterior PMs in nr2f1a; nr2f2 mutants. Our studies reveal insights into the molecular etiology that may underlie developmental syndromes that share heart, neck and facial defects as well as the phenotypic variability of congenital heart defects associated with NR2F mutations in humans.

PMID:
30721228
DOI:
10.1371/journal.pgen.1007962
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