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Patterning in stratified epithelia depends on cell-cell adhesion.

Yosuke Mai1, Yasuaki Kobayashi2,3, Hiroyuki Kitahata4

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Summary

Cell-cell adhesion drives the self-organization of epithelial cells into patterns. This process, known as cell-cell adhesion-induced patterning (CAIP), influences cell behavior and tissue structure, revealing intrinsic epithelial properties.

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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.