Journal
DIFFERENTIATION
Volume 77, Issue 3, Pages 298-306Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.diff.2008.10.006
Keywords
EGF receptor; Transgenic mouse; Salivary gland; Branching morphogenesis; Apoptosis; Gefitinib; MMP2; Plasminogen activator
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Funding
- Sigrid Juselius
- Finnish Medical Foundation
- Helsinki Hospital District Research Funds
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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. (C) 2008 International Society of Differentiation. Published by Elsevier Ltd. All rights reserved.
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