In vivo analysis of cardiomyocyte proliferation during trabeculation

Area of Science:

• Cardiology
• Developmental Biology
• Cell Biology

Background:

• Cardiomyocyte proliferation is essential for cardiac development, patterning, and regeneration.
• Limited research exists on the in vivo behavior of dividing cardiomyocytes.

Purpose of the Study:

• To investigate the in vivo behavior of proliferating cardiomyocytes in developing zebrafish.
• To identify distinct proliferation mechanisms in compact and trabecular myocardial layers.

Main Methods:

• Utilized time-lapse imaging of beating zebrafish hearts.
• Employed the FUCCI system to monitor cardiomyocyte cell cycle status.
• Observed sarcomere disassembly, cell shape/volume changes, and division orientation.

Main Results:

• Confirmed in vitro findings: sarcomere disassembly, shape/volume changes precede cytokinesis.
• Zebrafish cardiomyocytes primarily divide parallel to the myocardial wall in both compact and trabecular layers.
• Cardiomyocyte proliferation is more frequent in the trabecular layer.
• Nrg/ErbB2 and TGFβ signaling pathways differentially regulate proliferation in compact vs. trabecular layers.

Conclusions:

• Cardiomyocyte proliferation is crucial for trabecular growth, but not initiation, in zebrafish.
• Distinct molecular mechanisms drive proliferation in different myocardial layers.
• This study provides a foundation for further in vivo investigation of cardiomyocyte proliferation.