PUBLICATION

Nr2f-dependent allocation of ventricular cardiomyocyte and pharyngeal muscle progenitors

Authors
Dohn, T.E., Ravisankar, P., Tirera, F.T., Martin, K.E., Gafranek, J.T., Duong, T.B., VanDyke, T.L., Touvron, M., Barske, L.A., Crump, J.G., Waxman, J.S.
ID
ZDB-PUB-190206-14
Date
2019
Source
PLoS Genetics   15: e1007962 (Journal)
Registered Authors
Barske, Lindsey, Crump, Gage DeKoeyer, Waxman, Joshua
Keywords
none
MeSH Terms
  • Body Patterning/genetics
  • Mutation
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Pharyngeal Muscles/cytology
  • Pharyngeal Muscles/embryology
  • Pharyngeal Muscles/metabolism*
  • Cell Lineage/genetics
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Myocytes, Cardiac/cytology
  • Myocytes, Cardiac/metabolism*
  • Mesoderm/cytology
  • Mesoderm/embryology
  • Mesoderm/metabolism
  • Promoter Regions, Genetic
  • Animals, Genetically Modified
  • Animals
  • DNA-Binding Proteins/genetics
  • DNA-Binding Proteins/metabolism*
  • Heart Ventricles/cytology
  • Heart Ventricles/embryology
  • Heart Ventricles/metabolism
  • Signal Transduction
  • Humans
  • Craniofacial Abnormalities/embryology
  • Craniofacial Abnormalities/genetics
  • Models, Animal
  • Transcription Factors/genetics
  • Transcription Factors/metabolism*
  • COUP Transcription Factor II/genetics
  • COUP Transcription Factor II/metabolism*
  • Heart Defects, Congenital/embryology
  • Heart Defects, Congenital/genetics
  • Tretinoin/metabolism
  • Embryonic Stem Cells/cytology
  • Embryonic Stem Cells/metabolism
(all 38)
PubMed
30721228 Full text @ PLoS Genet.
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.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping