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Updated: Jun 30, 2026

Bead Aggregation Assays for the Characterization of Putative Cell Adhesion Molecules
Published on: October 17, 2014
New insights into cadherin function in epidermal sheet formation and maintenance of tissue integrity
Christopher L Tinkle1, H Amalia Pasolli, Nicole Stokes
1Laboratory of Mammalian Cell Biology and Development, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
Abstract:
Co-expression and gene linkage have hampered elucidating the physiological relevance of cadherins in mammalian tissues. Here, we combine conditional gene ablation and transgenic RNA interference to uncover new roles for E- and P-cadherins in epidermal sheet formation in vitro and maintenance of epidermal integrity in vivo. By devising skin-specific RNAi technology, we demonstrate that cadherin inhibition in vivo impairs junction formation and intercellular adhesion and increases apoptosis. These defects compromise epidermal barrier function and tissue integrity. In vitro, with only E-cadherin missing, epidermal sheet formation is delayed, but when both cadherins are suppressed, defects extend to adherens junctions, desmosomes, tight junctions and cortical actin dynamics. Using different rescue strategies, we show that cadherin level rather than subtype is critical. Finally, by comparing conditional loss-of-function studies of epidermal catenins and cadherins, we dissect cadherin-dependent and independent roles of adherens junction components in tissue physiology.
Insights
This study reveals new functions for E- and P-cadherins in skin. Cadherin suppression impairs skin barrier function and tissue integrity, highlighting their critical roles in epidermal health.
Area of Science:
- Cell Biology
- Developmental Biology
- Dermatology
Background:
- Cadherins are crucial for cell adhesion but their specific roles in mammalian tissues are complex due to co-expression and gene linkage.
- Understanding cadherin function is vital for tissue development and maintenance, particularly in the epidermis.
Purpose of the Study:
- To elucidate the physiological relevance of E-cadherin and P-cadherin in epidermal sheet formation and tissue integrity.
- To investigate the impact of cadherin suppression on junction formation, apoptosis, and epidermal barrier function.
Main Methods:
- Utilized conditional gene ablation and transgenic RNA interference (RNAi) for targeted gene manipulation in skin.
- Developed skin-specific RNAi technology to inhibit cadherin expression in vivo.
- Performed in vitro studies on epidermal sheet formation and in vivo assessments of epidermal integrity.
Main Results:
- Cadherin inhibition in vivo led to impaired junction formation, reduced intercellular adhesion, and increased apoptosis, compromising epidermal barrier function.
- In vitro, loss of E-cadherin delayed epidermal sheet formation, while combined loss of E- and P-cadherins disrupted multiple junction types and actin dynamics.
- Cadherin level, not subtype, was found to be critical for these functions.
- Dissected cadherin-dependent and independent roles of adherens junction components.
Conclusions:
- E- and P-cadherins are essential for epidermal integrity and barrier function.
- Cadherin levels are critical determinants of epidermal homeostasis.
- Adherens junction components have both cadherin-dependent and independent roles in tissue physiology.
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