Desmosomal cadherin misexpression alters beta-catenin stability and epidermal differentiation.
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 beta-catenin stability. Stabilized beta-catenin and increased beta-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 beta-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.
Hardman
Matthew J
MJ
Clinical Sciences Research Centre, University of London, 2 Newark St., London E1 2AT, United Kingdom.
Liu
Ke
K
Avilion
Ariel A
AA
Merritt
Anita
A
Brennan
Keith
K
Garrod
David R
DR
Byrne
Carolyn
C
D000505:Alopecia / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D051187:Desmocollins; D051182:Desmogleins; D051180:Desmoplakins; D003896:Desmosomes / Q000378:metabolism / Q000648:ultrastructure; D004817:Epidermis / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D005786:Gene Expression Regulation / Q000235:genetics; D018859:Hair Follicle / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D015603:Keratinocytes / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008822:Mice, Transgenic; D016253:Microscopy, Immunoelectron; D015534:Trans-Activators / Q000378:metabolism*; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D051187:Desmocollins; D051182:Desmogleins; D051180:Desmoplakins; D015534:Trans-Activators; D051176:beta Catenin