Activation of cell adhesion molecules and Snail during epithelial to mesenchymal transition prior to formation of the regenerative tail blastema in lizards.

Abstract

After few days from tail amputation in lizards the stump is covered with mesenchymal cells accumulated underneath a wound epidermis and forms a regenerative blastema. During migration, some keratinocytes transit from a compact epidermis into relatively free keratinocytes in a process of "epithelial to mesenchymal transition" (EMT). EMT is also induced after damaging the regenerating epidermis by cauterization, whereas keratinocytes detach and migrate as mesenchymal-like cells among the superficial blastema cells and reconstruct a wound epidermis after about a week from the damage. In normal amputation or after cauterization, no malignant transformation is observed during the transition and migration of keratinocytes. Immunolabeling for markers of EMT confirms the histological description and shows a unique pattern of expression for l-CAM (E-cadherin), N-CAM, and SNAIL-1 and -2 (SLUG). These proteins are present in the cytoplasm and nuclei of migrating keratinocytes. It is hypothesized that the nuclear labeling for E-cadherin coupled to cytoplasmic SNAIL-labeling is somehow related to an initially regulated EMT. After the migrating keratinocytes have reached confluence over the stump, they reverse into a "mesenchymal to epithelial transition" (MET) forming the wound epidermis. The basal layers of the apical wound epidermis of the blastema show some nuclear E-cadherin labeling, while the tail regenerates. It is hypothesized that, together with other tumor suppressors proteins, the apical epidermis and mesenchyme are kept under a tight proliferative control, while in proximal regions the prevalent effect of tumor suppressors determine the differentiation of the new tail tissues.