ZFIN ID: ZDB-PUB-171122-3
Nr2f1a balances atrial chamber and atrioventricular canal size via BMP signaling-independent and -dependent mechanisms
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.
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:
  • Animals
  • Bone Morphogenetic Proteins/genetics
  • Bone Morphogenetic Proteins/metabolism*
  • DNA-Binding Proteins/genetics
  • DNA-Binding Proteins/metabolism*
  • Heart Atria/embryology
  • Heart Atria/pathology
  • Heart Septal Defects, Atrial/embryology*
  • Heart Septal Defects, Atrial/genetics
  • Heart Septal Defects, Atrial/pathology
  • Humans
  • Myocytes, Cardiac/metabolism*
  • Myocytes, Cardiac/pathology
  • Signal Transduction*
  • Transcription Factors/genetics
  • Transcription Factors/metabolism*
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 29157563 Full text @ Dev. Biol.
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.