Real-time 3D visualization of cellular rearrangements during cardiac valve formation.
During cardiac valve development, the single-layered endocardial sheet at the atrioventricular canal (AVC) is remodeled into multilayered immature valve leaflets. Most of our knowledge about this process comes from examining fixed samples that do not allow a real-time appreciation of the intricacies of valve formation. Here, we exploit non-invasive in vivo imaging techniques to identify the dynamic cell behaviors that lead to the formation of the immature valve leaflets. We find that in zebrafish, the valve leaflets consist of two sets of endocardial cells at the luminal and abluminal side, which we refer to as luminal cells (LCs) and abluminal cells (ALCs), respectively. By analyzing cellular rearrangements during valve formation, we observed that the LCs and ALCs originate from the atrium and ventricle, respectively. Furthermore, we utilized Wnt/β-catenin and Notch signaling reporter lines to distinguish between the LCs and ALCs, and also found that cardiac contractility and/or blood flow is necessary for the endocardial expression of these signaling reporters. Thus, our 3D analyses of cardiac valve formation in zebrafish provide fundamental insights into the cellular rearrangements underlying this process.
Max Planck Institute for Heart and Lung Research, Department of Developmental Genetics, Bad Nauheim 61231, Germany.
Jenny
J
Pestel
Max Planck Institute for Heart and Lung Research, Department of Developmental Genetics, Bad Nauheim 61231, Germany.
Radhan
R
Ramadass
Max Planck Institute for Heart and Lung Research, Department of Developmental Genetics, Bad Nauheim 61231, Germany.
Sebastien
S
Gauvrit
Max Planck Institute for Heart and Lung Research, Department of Developmental Genetics, Bad Nauheim 61231, Germany University of Muenster, Muenster 48149, Germany.
Christian
C
Helker
University of Muenster, Muenster 48149, Germany Cells-in-Motion Cluster of Excellence (EXC 1003 - CiM), University of Muenster, Muenster 48149, Germany.
Wiebke
W
Herzog
Max Planck Institute for Heart and Lung Research, Department of Developmental Genetics, Bad Nauheim 61231, Germany didier.stainier@mpi-bn.mpg.de.
Didier Y R
0000-0002-0382-0026
DY
Stainier
D000818:Animals; D002465:Cell Movement; D003326:Coronary Circulation; D004699:Endocardium / Q000166:cytology / Q000196:embryology; D018507:Gene Expression Regulation, Developmental; D006325:Heart Atria / Q000166:cytology / Q000196:embryology; D006351:Heart Valves / Q000166:cytology* / Q000196:embryology*; D006352:Heart Ventricles / Q000166:cytology / Q000196:embryology; D021621:Imaging, Three-Dimensional; D009154:Mutation / Q000235:genetics; D009200:Myocardial Contraction; D038081:Organogenesis / Q000235:genetics; D051880:Receptors, Notch / Q000378:metabolism; D060449:Wnt Signaling Pathway; D015027:Zebrafish
D051880:Receptors, Notch
Apc; Cardiac valves; Endocardium; Live imaging; Notch; Wnt; Zebrafish