Mesenchyme-derived signals influence the unique keratinization and appendage formation programs in specialized skin regions. Interactions between primary mammary mesenchyme and epidermal cells result in the formation of the nipple; however, it is unclear whether this represents a site of regionally specialized epidermis. We profiled the ultrastructure and keratin expression of the murine nipple, and the ventral skin of the K14-parathyroid hormone-related protein (PTHrP) transgenic mouse, which models nipple formation. We found the murine nipple and ventral K14-PTHrP epidermis display expanded suprabasal and granular layers, as well as a thickened cornified layer compared to ventral skin of wild-type littermates. We also observed increased levels of filaggrin in extracts from the ventral epidermis of the K14-PTHrP mouse when compared to that of wild-type littermates. Keratin 2e, previously reported to be expressed in various specialized epidermal sites in the mouse, is expressed in the nipple and the ventral skin of the K14-PTHrP mouse. Keratinocytes grown from the ventral epidermis of the K14-PTHrP mouse or wild-type littermates exhibited identical expression of epidermal markers in vitro, suggesting that the modulated differentiation profile observed in the nipple or the ventral K14-PTHrP skin was dependent on interactions with fibroblasts. The lack of appendages, altered stratification pattern and expression of a specialized keratin suggests that the murine nipple is an example of regionally specialized epidermis.
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