Notch and Bmp signaling pathways act coordinately during the formation of the proepicardium

Area of Science:

• Developmental biology
• Cardiovascular research
• Signaling pathways

Background:

• The epicardium, the heart's outer mesothelial layer, is vital for cardiac development and regeneration.
• Epicardium originates from proepicardium (PE) cell clusters originating in the dorsal pericardium (DP).
• Bone morphogenetic protein (Bmp) and Notch signaling are known to influence PE formation, but their interaction remains unclear in zebrafish.

Purpose of the Study:

• To elucidate the interaction between Notch and Bmp signaling pathways during proepicardium formation in zebrafish.
• To investigate the role of endothelial Notch signaling in initiating proepicardium development.

Main Methods:

• Investigated the effects of Notch signaling manipulation (overexpression and inhibition) in zebrafish endothelium.
• Assessed Bmp expression levels and pSmad1/5 positive cell counts in response to Notch signaling changes.
• Utilized Bmp2b overexpression and Notch gain-of-function experiments to evaluate rescue capabilities.

Main Results:

• Endothelial Notch signaling positively influences PE formation by enhancing Bmp expression.
• Notch receptor overexpression in endothelium increased Bmp expression and PE cell numbers.
• Notch inhibition impaired PE formation, while Bmp2b overexpression could rescue this defect, but Notch gain-of-function could not rescue Bmp signaling deficiency.

Conclusions:

• Endothelial Notch signaling acts upstream of Bmp signaling to promote proepicardium formation.
• The study demonstrates a sequential activation: Endothelial Notch signaling activates Bmp expression in the heart tube, which subsequently induces PE cluster formation from the dorsal pericardium.