The adhesive core of the desmosome is composed of cadherin-like glycoproteins of 2 families, desmocollins and desmogleins. The desmosomal cadherins show distinct patterns of expression in adult epidermis, and we have suggested that the desmocollins have a functional role in regulating the differentiation and/or morphogenesis of that epithelium (North et al. [1996] Proc. Natl. Acad. Sci. USA 93:7701-7705.). To examine this hypothesis, we cloned murine desmocollins and examined the induction patterns of desmocollins 1 and 3 during skin and skin appendage development. Desmocollins 3 and 1 were first expressed in epidermis in highly regional patterns at embryonic days 13.0 and 13.5, respectively, and both were up-regulated in general body epidermis at day 14.5. At this stage, epidermis is undifferentiated and the desmocollins showed an unexpected expression pattern. However, by day 18.5 when skin had undergone terminal differentiation, desmocollin 1 and 3 expression resembled that found in the adult. Thus, the establishment of the adult pattern of desmocollin expression corresponds to the adult pattern of epidermal stratification. We suggest that it is the ratio of desmocollin 1 to desmocollin 3 expression at different levels in the epidermis that is fundamental in establishing this pattern of differentiation.