New insights into cadherin function in epidermal sheet formation and maintenance of tissue integrity. Academic Article uri icon

Overview

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.

publication date

  • September 22, 2008

Research

keywords

  • Cadherins
  • Epidermis

Identity

PubMed Central ID

  • PMC2547466

Scopus Document Identifier

  • 55749101603

Digital Object Identifier (DOI)

  • 10.1073/pnas.0807374105

PubMed ID

  • 18809908

Additional Document Info

volume

  • 105

issue

  • 40