Microarray analysis demonstrates a role for Slug in epidermal homeostasis.
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.
Newkirk
Kimberly M
KM
Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, USA. knewkirk@utk.edu
MacKenzie
Debra A
DA
Bakaletz
Alan P
AP
Hudson
Laurie G
LG
Kusewitt
Donna F
DF
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D000078404:Epidermal Cells; D004817:Epidermis / Q000502:physiology*; D005260:Female; D006706:Homeostasis / Q000502:physiology*; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2
D015815:Cell Adhesion Molecules; C498520:Gli1 protein, mouse; C000618551:Gli2 protein, mouse; D051741:Kruppel-Like Transcription Factors; D018123:Receptors, Interleukin; C000604429:Snai1 protein, mouse; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2