title: Serum response factor controls transcriptional network regulating epidermal function and hair follicle morphogenesis.
abstract: Serum response factor (SRF) is a transcription factor that regulates the expression of growth-related immediate-early, cytoskeletal, and muscle-specific genes to control growth, differentiation, and cytoskeletal integrity in different cell types. To investigate the role for SRF in epidermal development and homeostasis, we conditionally knocked out SRF in epidermal keratinocytes. We report that SRF deletion disrupted epidermal barrier function leading to early postnatal lethality. Mice lacking SRF in epidermis displayed morphogenetic defects, including an eye-open-at-birth phenotype and lack of whiskers. SRF-null skin exhibited abnormal morphology, hyperplasia, aberrant expression of differentiation markers and transcriptional regulators, anomalous actin organization, enhanced inflammation, and retarded hair follicle (HF) development. Transcriptional profiling experiments uncovered profound molecular changes in SRF-null E17.5 epidermis and revealed that many previously identified SRF target CArG box-containing genes were markedly upregulated in SRF-null epidermis, indicating that SRF may function to repress transcription of a subset of its target genes in epidermis. Remarkably, when transplanted onto nude mice, engrafted SRF-null skin lacked hair but displayed normal epidermal architecture with proper expression of differentiation markers, suggesting that although keratinocyte SRF is essential for HF development, a cross-talk between SRF-null keratinocytes and the surrounding microenvironment is likely responsible for the barrier-deficient mutant epidermal phenotype.
authors.affiliation: Division of Dermatology, Department of Internal Medicine, Washington University School of Medicine, St Louis, Missouri, USA.
authors.forename: Congxing
authors.initials: C
authors.lastname: Lin
authors.affiliation: Division of Dermatology, Department of Internal Medicine, Washington University School of Medicine, St Louis, Missouri, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Hindes
authors.affiliation: Division of Dermatology, Department of Internal Medicine, Washington University School of Medicine, St Louis, Missouri, USA.
authors.forename: Carole J
authors.initials: CJ
authors.lastname: Burns
authors.affiliation: Division of Dermatology, Department of Internal Medicine, Washington University School of Medicine, St Louis, Missouri, USA.
authors.forename: Aaron C
authors.initials: AC
authors.lastname: Koppel
authors.affiliation: Division of Dermatology, Department of Internal Medicine, Washington University School of Medicine, St Louis, Missouri, USA.
authors.forename: Alexi
authors.initials: A
authors.lastname: Kiss
authors.affiliation: Division of Dermatology, Department of Internal Medicine, Washington University School of Medicine, St Louis, Missouri, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Division of Dermatology, Department of Internal Medicine, Washington University School of Medicine, St Louis, Missouri, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Ma
authors.affiliation: R. O. Perelman Department of Dermatology, NYU School of Medicine, New York, New York, USA.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Blumenberg
authors.affiliation: Department of Pathology and Centre for Immune Regulation, University Hospital and University of Oslo, Oslo, Norway.
authors.forename: Denis
authors.initials: D
authors.lastname: Khnykin
authors.affiliation: Department of Pathology and Centre for Immune Regulation, University Hospital and University of Oslo, Oslo, Norway.
authors.forename: Frode L
authors.initials: FL
authors.lastname: Jahnsen
authors.affiliation: Department of Genetics, Washington University School of Medicine, St Louis, Missouri, USA.
authors.forename: Seth D
authors.initials: SD
authors.lastname: Crosby
authors.affiliation: Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, Missouri, USA.
authors.forename: Narendrakumar
authors.initials: N
authors.lastname: Ramanan
authors.affiliation: Division of Dermatology, Department of Internal Medicine, Washington University School of Medicine, St Louis, Missouri, USA. Electronic address: tefimova@dom.wustl.edu.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Efimova
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000502:physiology; D049109:Cell Proliferation; D004817:Epidermis / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D018859:Hair Follicle / Q000254:growth & development* / Q000502:physiology; D015603:Keratinocytes / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D023421:Models, Animal; D009024:Morphogenesis / Q000502:physiology*; D010641:Phenotype; D026362:Serum Response Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D026362:Serum Response Factor; D014157:Transcription Factors