Cell adhesion and junctional proteins in the developing skin of snakes indicate they coordinate the differentiation of the epidermis.

The development of scales and the sequence of epidermal layers during snake embryogenesis has been studied by immunofluorescence for the localization of cell adhesion, adherens, and communicating cell junctional proteins. At about 2nd/3rd of embryonic development in snakes the epidermis forms symmetric bumps at the beginning of scale formation, and they rapidly become asymmetric and elongate forming outer and inner surfaces of the very overlapped scales seen at hatching. The dermis separates a superficial loose from a deeper dense part; the latter is joined to segmental muscles and nerves, likely acting on scale orientation during snake movements. N-cam is present in the differentiating epidermis and mesenchyme of forming scales while L-cam is only/mainly detected in the periderm and epidermis. Mesenchymal N-cam is associated with the epidermis of the elongating dorsal scale surface and with the beta-differentiation that occurs in the overlapping outer surface of scales. Beta-catenin and Connexin-43 show a similar distribution, and they are mainly present in the periderm and differentiating suprabasal keratinocytes likely forming an intense connectivity during epidermal differentiation. Beta-catenin also shows nuclear localization in differentiating cells of the shedding and beta-layers at late stages of scale morphogenesis, before hatching. The study suggests that intensification of adhesion and gap junctions allows synchronization of the differentiation of suprabasal cells to produce the ordered sequence of epidermal layers of snake scales, starting from the shedding complex and the beta-layer.