Contractile forces at tricellular contacts modulate epithelial organization and monolayer integrity

Area of Science:

• Cell Biology
• Epithelial Biology
• Tissue Engineering

Background:

• Monolayered epithelia rely on tight cell assemblies for polarized function.
• Epithelial cell adhesion molecule (EpCAM) is an unconventional epithelial-specific molecule involved in morphogenesis.
• Cellular defects in EpCAM-related human intestinal disease highlight the need to understand EpCAM's cellular functions.

Purpose of the Study:

• To investigate the cellular functions of EpCAM in enterocytes.
• To elucidate the mechanisms underlying EpCAM-deficiency-related intestinal defects.
• To determine the role of EpCAM in maintaining epithelial monolayer organization and tissue architecture.

Main Methods:

• Analysis of cellular defects in a rare EpCAM-related human intestinal disease.
• Microscopic examination of enterocyte apical domain and tight junction organization.
• Assessment of actomyosin network homeostasis and contractile activity at tricellular contacts (TCs).
• Treatment with myosin-II inhibitors to observe reversal of defects.

Main Results:

• Absence of EpCAM in enterocytes leads to an aberrant apical domain and tight junction belt displacement.
• Loss of EpCAM causes actomyosin network imbalance and contractile activity clustering at TCs.
• Myosin-II inhibitor treatment reversed the observed cell organization defects and tissue abnormalities.
• Adequate cortical tension distribution is crucial for individual cell organization and epithelial monolayer maintenance.

Conclusions:

• EpCAM plays a critical role in maintaining epithelial cell organization and apical domain integrity.
• EpCAM deficiency disrupts actomyosin network homeostasis, leading to intestinal tissue defects.
• EpCAM modulation is protective against epithelial dysplasia and contributes to human tissue architecture stabilization.