Patterning in stratified epithelia depends on cell-cell adhesion.

Area of Science:

• Cell Biology
• Developmental Biology
• Biophysics

Background:

• Epithelial tissues exhibit complex spatial arrangements of proliferating and differentiating cells.
• The underlying mechanisms governing these multicellular patterns remain largely unknown.
• Understanding epithelial self-organization is crucial for developmental and regenerative biology.

Purpose of the Study:

• To investigate the role of cell-cell adhesion in regulating spatial patterning within stratified epithelia.
• To elucidate the molecular and biophysical factors contributing to epithelial self-organization.
• To explore the functional consequences of adhesion-induced patterning on cell behavior.

Main Methods:

• Culturing of human keratinocytes under starvation conditions.
• Pharmacological inhibition and genetic knockout of adherens junctions.
• Development and analysis of a mathematical model for cell-cell adhesion.
• Assessment of cell density, differentiation, proliferation, and Yes-associated protein (YAP) modulation.

Main Results:

• Starvation induced spontaneous, patterned arrangements of high and low cell density in cultured epithelia.
• Adherens junctions were identified as essential for this cell-cell adhesion-induced patterning (CAIP).
• A mathematical model confirmed that local cell-cell adhesion can generate density variations.
• CAIP influenced cell differentiation and proliferation, modulated by YAP.
• Induced CAIP enhanced epithelial stratification.

Conclusions:

• Cell-cell adhesion is a key intrinsic property driving the self-organization and patterning of epithelial cells.
• The phenomenon of CAIP provides a framework for understanding how simple adhesion forces create complex tissue architectures.
• These findings offer insights into epithelial morphogenesis and tissue homeostasis.