TY - JOUR
T1 - Platelet-derived growth factor signaling as a cue of the epithelial-mesenchymal interaction required for anuran skin metamorphosis
AU - Utoh, Rie
AU - Shigenaga, Sachi
AU - Watanabe, Yusuke
AU - Yoshizato, Katsutoshi
PY - 2003/6/1
Y1 - 2003/6/1
N2 - 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) -α 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-α 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-α 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.
AB - 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) -α 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-α 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-α 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.
KW - AG1296
KW - Connective tissue
KW - Epidermal basal cells
KW - Fibroblasts
KW - Larvae
KW - Platelet-derived growth factor receptor
KW - Thyroid hormone
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U2 - 10.1002/dvdy.10302
DO - 10.1002/dvdy.10302
M3 - Article
C2 - 12761844
AN - SCOPUS:0037945230
VL - 227
SP - 157
EP - 169
JO - American Journal of Anatomy
JF - American Journal of Anatomy
SN - 1058-8388
IS - 2
ER -