title: Heartbeat-driven pericardiac fluid forces contribute to epicardium morphogenesis.
abstract: BACKGROUND
  Hydrodynamic forces play a central role in organ morphogenesis. The role of blood flow in shaping the developing heart is well established, but the role of fluid forces generated in the pericardial cavity surrounding the heart is unknown. Mesothelial cells lining the pericardium generate the proepicardium (PE), the precursor cell population of the epicardium, the outer layer covering the myocardium, which is essential for its maturation and the formation of the heart valves and coronary vasculature. However, there is no evidence from in vivo studies showing how epicardial precursor cells reach and attach to the heart.
  
  
  RESULTS
  Using optical tools for real-time analysis in the zebrafish, including high-speed imaging and optical tweezing, we show that the heartbeat generates pericardiac fluid advections that drive epicardium formation. These flow forces trigger PE formation and epicardial progenitor cell release and motion. The pericardial flow also influences the site of PE cell adhesion to the myocardium. We additionally identify novel mesothelial sources of epicardial precursors and show that precursor release and adhesion occur both through pericardiac fluid advections and through direct contact with the myocardium.
  
  
  CONCLUSIONS
  Two hydrodynamic forces couple cardiac development and function: first, blood flow inside the heart, and second, the pericardial fluid advections outside the heart identified here. This pericardiac fluid flow is essential for epicardium formation and represents the first example of hydrodynamic flow forces controlling organogenesis through an action on mesothelial cells.
authors: Department of Cardiovascular Development and Repair, Centro Nacional de Investigaciones Cardiovasculares Carlos III, calle Melchor Fernández Almagro 3, 28029 Madrid, Spain.
authors: Marina
authors: M
authors: Peralta
authors: Emily
authors: E
authors: Steed
authors: Sébastien
authors: S
authors: Harlepp
authors: Juan Manuel
authors: JM
authors: González-Rosa
authors: Fabien
authors: F
authors: Monduc
authors: Ana
authors: A
authors: Ariza-Cosano
authors: Alfonso
authors: A
authors: Cortés
authors: Teresa
authors: T
authors: Rayón
authors: Jose-Luis
authors: JL
authors: Gómez-Skarmeta
authors: Agustín
authors: A
authors: Zapata
authors: Julien
authors: J
authors: Vermot
authors: Nadia
authors: N
authors: Mercader
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002454:Cell Differentiation; D047108:Embryonic Development; D006321:Heart / Q000033:anatomy & histology / Q000196:embryology / Q000502:physiology; D057446:Hydrodynamics; D009024:Morphogenesis; D009206:Myocardium / Q000166:cytology; D010496:Pericardium / Q000033:anatomy & histology / Q000196:embryology*; D012039:Regional Blood Flow; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D015027:Zebrafish / Q000033:anatomy & histology / Q000196:embryology*