Platelet-derived growth factor signaling as a cue of the epithelial-mesenchymal interaction required for anuran skin metamorphosis.

The anuran remodels the larval skin into the adult counterpart during metamorphosis. The construction of the precursor of adult epidermis (preadult epidermis) in Xenopus laevis larvae was coordinated with the development of the secondary connective tissue (s-ct) underneath the basement membrane, suggesting that the epithelial-mesenchymal interaction plays a critical role in the metamorphic conversion of the larval skin. mRNAs of platelet-derived growth factor A (PDGF-A) and PDGF receptor (PDGFR) -alpha were markedly up-regulated in the skin during spontaneous and thyroid hormone (TH) -induced metamorphosis. In situ hybridization experiments identified preadult epidermal basal cells and fibroblasts in developing subepidermal connective tissues at the late prometamorphic stage as PDGF-A and PDGFR-alpha mRNA-expressing cells, respectively. We developed an in vitro model of larval skin that was remodeled to the adult skin under the influence of TH. The presence of either of AG1296, a specific inhibitor of PDGFR tyrosine kinase autophosphorylation, or an excess of recombinant proteins of the soluble extracellular domain of PDGFR-alpha inhibited the following TH-induced processes, the proliferation of adult basal cells, the terminal differentiation of adult basal cells, and the activation of subepidermal fibroblasts. However, the inhibitors did not inhibit the TH-induced proliferation of preadult basal cells. We concluded that PDGF/PDGFR signaling is one of the prime cues in the epithelial-mesenchymal interaction required for the metamorphic skin remodeling.