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Publication : New insights into cadherin function in epidermal sheet formation and maintenance of tissue integrity.

First Author  Tinkle CL Year  2008
Journal  Proc Natl Acad Sci U S A Volume  105
Issue  40 Pages  15405-10
PubMed ID  18809908 Mgi Jnum  J:144091
Mgi Id  MGI:3830113 Doi  10.1073/pnas.0807374105
Citation  Tinkle CL, et al. (2008) New insights into cadherin function in epidermal sheet formation and maintenance of tissue integrity. Proc Natl Acad Sci U S A 105(40):15405-10
abstractText  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.
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