Heartbeat-driven pericardiac fluid forces contribute to epicardium morphogenesis

Area of Science:

• Developmental Biology
• Cardiovascular Research
• Biophysics

Background:

• Hydrodynamic forces are critical for organ development, with blood flow's role in heart formation established.
• The influence of fluid forces within the pericardial cavity on heart development remains largely unknown.
• Mesothelial cells in the pericardium form the proepicardium (PE), essential for epicardial development and heart maturation.

Purpose of the Study:

• To investigate the role of pericardial fluid forces in epicardium formation.
• To elucidate the mechanisms by which epicardial precursor cells reach and attach to the developing heart.
• To identify novel sources of epicardial precursors and their migratory behavior.

Main Methods:

• Utilized optical tools for real-time analysis in zebrafish.
• Employed high-speed imaging and optical tweezing techniques.
• Observed pericardiac fluid advections and their impact on PE cell behavior.

Main Results:

• Heartbeat-generated pericardiac fluid advections drive epicardium formation.
• Flow forces stimulate PE formation, epicardial progenitor cell release, and motion.
• Pericardial flow influences PE cell adhesion sites and identifies novel mesothelial precursor sources.

Conclusions:

• Two hydrodynamic forces govern cardiac development: internal blood flow and external pericardial fluid advections.
• Pericardial fluid flow is essential for epicardium formation, demonstrating hydrodynamic control over organogenesis via mesothelial cells.
• This study reveals a novel mechanism where external fluid dynamics regulate heart development.