Format

Send to

Choose Destination
Curr Biol. 2013 Sep 23;23(18):1726-35. doi: 10.1016/j.cub.2013.07.005. Epub 2013 Aug 15.

Heartbeat-driven pericardiac fluid forces contribute to epicardium morphogenesis.

Author information

1
Department of Cardiovascular Development and Repair, Centro Nacional de Investigaciones Cardiovasculares Carlos III, calle Melchor Fernández Almagro 3, 28029 Madrid, Spain.

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.

PMID:
23954432
DOI:
10.1016/j.cub.2013.07.005
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center