Characterization ofWntGene Expression in Murine Skin: Possible Involvement of Epidermis-Derived Wnt-4 in Cutaneous Epithelial–Mesenchymal Interactions

Wnt glycoproteins mediate short range intracellular communication that facilitates morphogenesis and, in some settings, promotes tumor formation. Although the involvement of theDrosophilahomolog wingless in ectodermal patterning is well established, the role thatWntgenes play in mammalian skin biology is not defined. We detectedWnt-4andWnt-10bmRNA in adult murine epidermis using degenerate primers and reverse transcriptase PCR, and confirmed expression by RNase protection. Normal murine keratinocytes and a melanocyte cell line (melan-A) propagatedin vitroalso containedWnt-4mRNA, whereas dermal fibroblasts and Langerhans cell-like dendritic cells did not. BecauseWnt-4mRNA was more abundant thanWnt-10bmRNA in epidermis andWnt-10btrancripts were not detected in cells propagatedin vitro,additional studies emphasizedWnt-4exclusively.Wnt-4mRNA levels were increased in cultured keratinocytes as they approached confluence and were strikingly downregulated by mitogenic growth factors. AlthoughWnt-4mRNA levels were not modulated during calcium-induced keratinocyte differentiationin vitro,assessment ofWnt-4transcripts in keratinocyte cell lines suggested that loss ofWnt-4gene expression was associated with a less differentiated, more malignant, phenotype. Despite this, epidermal abnormalities were not identified in newbornWnt-4null (−/−) skin, or in full-thickness −/− skin that was engrafted to nude or athymic mice and allowed to mature for as long as 3 months. However, histologic examination of newbornWnt-4null skin did reveal fibroplasia involving the dermis with increased accumulation of type I collagen fibrils. These results indicate that severalWntgenes are expressed in adult murine epidermis and suggest that Wnt-4 proteins may be involved in epidermal–dermal interactions in mammalian skin.