Mesothelial mobilization in the developing lung and heart differs in timing, quantity, and pathway dependency

Area of Science:

• Developmental Biology
• Cell Biology
• Molecular Biology

Background:

• The mesothelium lining the lung (visceral pleura) and heart (epicardium) originates from a common embryonic precursor.
• Mesothelial mobilization and differentiation are well-studied in the heart but poorly understood in the lung.

Purpose of the Study:

• To comparatively analyze mesothelial mobilization in the developing lung and heart.
• To investigate the signaling pathways involved in visceral pleural mesothelial transition.

Main Methods:

• Utilized a Wt1-driven cre-loxP genetic approach for conditional mesothelial inactivation.
• Analyzed mesothelial mobilization timing, quantity, and pathway dependency in lung and heart development.

Main Results:

• Epicardial mobilization is extensive (E12.5-E14.5); pleural mobilization is sporadic and temporally restricted (shortly after E12.5).
• Canonical WNT, NOTCH, HH, TGFB, PDGFRA, and FGFR1/2 signaling are not required for visceral pleural mesenchymal transition.
• Activated WNT, NOTCH, and HH signaling negatively impact lung development, while their loss affects epicardial mobilization.

Conclusions:

• Mesothelial mobilization in lung and heart development differs significantly in timing, quantity, and pathway requirements.
• These differences underscore the organ-specific nature of developmental programs governing mesothelial fate.