Published online before print June 13, 2008

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(American Journal of Pathology. 2008;173:14-24.)
© 2008 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2008.070942

Review

Beyond Wavy Hairs

The Epidermal Growth Factor Receptor and Its Ligands in Skin Biology and Pathology

Marlon R. Schneider^*, Sabine Werner, Ralf Paus and Eckhard Wolf^*

From the Institute of Molecular Animal Breeding and Biotechnology and Laboratory for Functional Genome Analysis,^* Gene Center, LMU Munich, Munich, Germany; the Department of Dermatology, University Hospital Schleswig-Holstein, University of Lübeck, Lübeck, Germany; the Department of Biology, Institute of Cell Biology, ETH Zurich, Zürich, Switzerland; and the School of Translational Medicine, University of Manchester, Manchester, United Kingdom

Abstract

The epidermal growth factor receptor (EGFR) network, including its seven ligands and four related receptors, represents one of the most complex signaling systems in biology. In many tissues, including the skin and its appendages (notoriously the hair follicles), its correct function is necessary for proper development and tissue homeostasis, and its deregulation rapidly results in defects in cellular proliferation and differentiation. The consequences are impaired wound healing, development of psoriasis-like lesions, structural and functional defects of the hair follicles, and tumorigenesis. In addition to in vitro experiments and data from clinical studies, several genetically modified mouse models displaying alterations in the interfollicular skin and hair follicles attributable to mutations in components of the EGFR system have been reported. These animals, in many cases representing bona fide models of known human diseases, have been seminal in the study of the role of EGFR and its ligands in the skin and its appendages. In this review, we take the multiple phenotypes of these animal models as a basis to summarize and discuss the effects elicited by members of the EGFR system in diverse aspects of skin biology and pathology, including cellular proliferation and differentiation, wound healing, hair follicle morphogenesis, and tumorigenesis.