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Molecular and Cellular Biology, February 2005, p. 969-978, Vol. 25, No. 3
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.3.969-978.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Desmosomal Cadherin Misexpression Alters ß-Catenin Stability and Epidermal Differentiation

Matthew J. Hardman,1 Ke Liu,2 Ariel A. Avilion,3 Anita Merritt,1 Keith Brennan,1 David R. Garrod,1 and Carolyn Byrne4*

Faculty of Life Sciences, University of Manchester, Manchester,1 Gene Targeting Unit, Imperial College School of Medicine,2 ,3 Queen Mary School of Medicine and Dentistry, University of London, London, United Kingdom4

Received 20 August 2004/ Accepted 4 October 2004

Desmosomal adhesion is important for the integrity and protective barrier function of the epidermis and is disregulated during carcinogenesis. Strong adhesion between keratinocytes is conferred by the desmosomal cadherins, desmocollin (Dsc) and desmoglein. These constitute two gene families, members of which are differentially expressed in epidermal strata. It has been suggested that this stratum-specific expression regulates keratinocyte differentiation. We tested this hypothesis by misdirecting the expression of the basally abundant desmosomal cadherins Dsc3a and Dsc3b to suprabasal differentiating keratinocytes in transgenic mice. No phenotype was apparent until adulthood, when mice developed variable ventral alopecia and had altered keratinocyte differentiation within affected areas. The follicular changes were reminiscent of changes in transgenic mice with an altered ß-catenin stability. Stabilized ß-catenin and increased ß-catenin transcriptional activity were demonstrated in transgenic mice prior to the phenotypic change and in transgenic keratinocytes as a consequence of transgene expression. Hence, a link between desmosomal cadherins and ß-catenin stability and signaling was demonstrated, and it was shown that desmocollin cadherin expression can affect keratinocyte differentiation. Furthermore, the first function for a "b-type" desmocollin cadherin was demonstrated.

* Corresponding author. Mailing address: Clinical Sciences Research Centre, University of London, 2 Newark St., London E1 2AT, United Kingdom. Phone: 44 (0)2078827165. Fax: 44(0)2078827171. E-mail: C.R.Byrne{at}qmul.ac.uk.

Molecular and Cellular Biology, February 2005, p. 969-978, Vol. 25, No. 3
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.3.969-978.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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