PUBLICATION

Nr2f1a balances atrial chamber and atrioventricular canal size via BMP signaling-independent and -dependent mechanisms

Authors
Duong, T.B., Ravisankar, P., Song, Y.C., Gafranek, J.T., Rydeen, A.B., Dohn, T.E., Barske, L.A., Crump, J.G., Waxman, J.S.
ID
ZDB-PUB-171122-3
Date
2017
Source
Developmental Biology   434(1): 7-14 (Journal)
Registered Authors
Barske, Lindsey, Crump, Gage DeKoeyer, Waxman, Joshua
Keywords
Nr2f1a, atrial myocardium, atrioventricular canal, cardiac chambers, valve development, zebrafish
MeSH Terms
  • DNA-Binding Proteins/genetics
  • DNA-Binding Proteins/metabolism*
  • Heart Atria/embryology
  • Heart Atria/pathology
  • Myocytes, Cardiac/metabolism*
  • Myocytes, Cardiac/pathology
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Humans
  • Signal Transduction*
  • Bone Morphogenetic Proteins/genetics
  • Bone Morphogenetic Proteins/metabolism*
  • Heart Septal Defects, Atrial/embryology*
  • Heart Septal Defects, Atrial/genetics
  • Heart Septal Defects, Atrial/pathology
  • Animals
  • Transcription Factors/genetics
  • Transcription Factors/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
(all 20)
PubMed
29157563 Full text @ Dev. Biol.
Abstract
Determination of appropriate chamber size is critical for normal vertebrate heart development. Although Nr2f transcription factors promote atrial maintenance and differentiation, how they determine atrial size remains unclear. Here, we demonstrate that zebrafish Nr2f1a is expressed in differentiating atrial cardiomyocytes. Zebrafish nr2f1a mutants have smaller atria due to a specific reduction in atrial cardiomyocyte (AC) number, suggesting it has similar requirements to Nr2f2 in mammals. Furthermore, the smaller atria in nr2f1a mutants are derived from distinct mechanisms that perturb AC differentiation at the chamber poles. At the venous pole, Nr2f1a enhances the rate of AC differentiation. Nr2f1a also establishes the atrial-atrioventricular canal (AVC) border through promoting the differentiation of mature ACs. Without Nr2f1a, AVC markers are expanded into the atrium, resulting in enlarged endocardial cushions (ECs). Inhibition of Bmp signaling can restore EC development, but not AC number, suggesting that Nr2f1a concomitantly coordinates atrial and AVC size through both Bmp-dependent and independent mechanisms. These findings provide insight into conserved functions of Nr2f proteins and the etiology of atrioventricular septal defects (AVSDs) associated with NR2F2 mutations in humans.
Genes / Markers
Figures
Figure Gallery (7 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ci1009
    Small Deletion
    el512
      Small Deletion
      f2TgTransgenic Insertion
        sd22TgTransgenic Insertion
          1 - 4 of 4
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          Human Disease / Model
          No data available
          Sequence Targeting Reagents
          Target Reagent Reagent Type
          nr2f1aCRISPR1-nr2f1aCRISPR
          nr2f1aTALEN1-nr2f1aTALEN
          1 - 2 of 2
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          Fish
          Antibodies
          Orthology
          Engineered Foreign Genes
          Marker Marker Type Name
          DsRed2EFGDsRed2
          KaedeEFGKaede
          1 - 2 of 2
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          Mapping