EGF-receptor regulates salivary gland branching morphogenesis by supporting proliferation and maturation of epithelial cells and survival of mesenchymal cells.
Epidermal growth factor receptor (EGF-R) regulates epithelial morphogenesis during development and is important for the proper branching of the lung, mammary gland, and pancreas. We analyzed the salivary gland phenotype of EGF-R-deficient mice and showed impaired growth, branching, and maturation of the epithelium. Furthermore, treatment of wild-type E13 salivary glands with gefitinib, a small molecular inhibitor of EGF-R, led to apoptosis of the mesenchyme. Interestingly, MMP2 and plasminogen activators were upregulated upon inhibition of EGF-R signaling. To summarize, we show that EGF-R is a physiological regulator of salivary gland development and its main function is to support the proliferation and maturation of the epithelium and the survival of the mesenchyme.
Häärä
Otso
O
Pediatric Research Unit, HUCH Hospital for Children and Adolescents, Biomedicum Helsinki, University of Helsinki, Room B428b, PO Box 63, FIN-00014 Helsinki, Finland.
Koivisto
Tarja
T
Miettinen
Päivi J
PJ
D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D002470:Cell Survival; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D009024:Morphogenesis / Q000235:genetics; D009924:Organ Culture Techniques; D012469:Salivary Glands / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D015854:Up-Regulation
D066246:ErbB Receptors