1. ¹Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, USA
2. ²Division of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Albuquerque, New Mexico, USA
3. ³College of Medicine and Public Health, The Ohio State University, Columbus, Ohio, USA

Correspondence: Dr K Newkirk, The University of Tennessee, College of Veterinary Medicine, 2407 River Drive, Room A201, Knoxville, Tennessee 37996-4542, USA. E-mail: knewkirk@utk.edu

Received 17 January 2007; Revised 1 May 2007; Accepted 28 May 2007; Published online 19 July 2007.

Abstract

Slug (Snail2) is a member of the Snail family of zinc-finger transcription factors with regulatory functions in development, tissue morphogenesis, and tumor progression. Little is known about Slug in normal adult tissue; however, a role for Slug in the skin was suggested by our previous observations of Slug expression in normal murine keratinocytes and Slug induction at wound margins. To study the impact of Slug in the skin, we compared patterns of gene expression in epidermis from Slug-null and wild-type mice. A total of 139 genes had significantly increased, and 109 genes had significantly decreased expression in Slug knockout epidermis. Altered expression of selected genes in Slug knockout epidermis was validated by real-time PCR and immunohistochemistry. Previously reported Slug targets were identified, in addition to novel genes, including cytokeratins, adhesion molecules, and extracellular matrix components. Functional classification of altered gene expression was consistent with a role for Slug in keratinocyte development and differentiation, proliferation, apoptosis, adhesion, motility, as well as angiogenesis and response to environmental stimuli. These results highlight the utility of genetic models to study the in vivo impact of regulatory factors in unperturbed skin and suggest that Slug has significant activities in the adult epidermis.