Coordinating cardiomyocyte interactions to direct ventricular chamber morphogenesis

Area of Science:

• Cardiovascular Biology
• Developmental Biology
• Cellular Signaling

Background:

• Heart ventricular walls have distinct compact and trabecular layers crucial for function.
• Disruptions in myocardial wall formation cause congenital heart diseases and cardiomyopathies.
• Mechanisms of embryonic cardiomyocyte spatial organization remain largely unknown.

Purpose of the Study:

• To elucidate the signaling pathways governing cardiomyocyte assembly in the developing zebrafish heart.
• To understand how myocardial Notch and Erbb2 signaling interact to direct cell positioning and morphogenesis.
• To reveal the cellular dynamics underlying ventricular wall formation.

Main Methods:

• Utilized advanced genetic manipulation and in vivo imaging in zebrafish models.
• Investigated cell-autonomous and non-cell-autonomous roles of Notch and Erbb2 signaling.
• Analyzed effects of manipulating myocardial Notch activity on ventricular morphology.

Main Results:

• Identified a feedback loop where myocardial Notch signaling inhibits Erbb2 signaling, preventing cardiomyocyte sprouting and trabeculation.
• Myocardial-specific Notch inactivation resulted in reduced ventricle size and thickened walls due to excessive trabeculae.
• Widespread myocardial Notch activity led to enlarged ventricles with thin walls and absent trabeculae.
• Erbb2-activated cardiomyocytes non-cell-autonomously activate myocardial Notch signaling.

Conclusions:

• A novel interactive cellular feedback process between Notch and Erbb2 signaling guides cardiomyocyte assembly.
• This signaling interplay is critical for establishing the spatial dimensions and myocardial mass of the ventricular wall.
• Findings provide insights into the cellular dynamics of tissue morphogenesis and organ form.