title: The epidermal growth factor receptor decreases Stathmin 1 and triggers catagen entry in the mouse.
abstract: The epidermal growth factor receptor (EGFR) is necessary for normal involution of hair follicles after the growth phase of anagen, although the mechanisms through which it acts are not well understood. In this report, we used transcriptional profiling of microdissected hair follicles from mice with skin-targeted deletion of Egfr to investigate how EGFR activation triggers catagen. Immunofluorescence for phospho-EGFR in mouse skin revealed increased activation of EGFR in follicular keratinocytes at catagen onset. Consistent with other models of EGFR deficiency, mice with skin-targeted deletion of Egfr (Krt14-Cre(+) /Egfr(fl/fl) ) exhibited a delayed and asynchronous catagen entry. Transcriptional profiling at the time of normal catagen onset at post-natal day (P) 17 revealed increased expression of the mitotic regulator Rcc2 in hair follicles lacking EGFR. Rcc2 protein was strongly immunopositive in the nuclei of control follicular keratinocytes at P16 then rapidly decreased until it was undetectable between P18 and 21. In contrast, Rcc2 expression continued in Egfr mutant follicles throughout this period. Proliferation, measured by bromodeoxyuridine incorporation, was also significantly increased in Egfr mutant follicular keratinocytes compared to controls at P18-21. Similarly, Rcc2-regulated mitotic regulator Stathmin 1 was strikingly reduced in control but not Egfr mutant follicles between P17 and P19. Deletion of Stmn1, in turn, accelerated catagen entry associated with premature cessation of proliferation in the hair follicles. These data reveal EGFR suppression of mitotic regulators including Rcc2 and Stathmin 1 as a mechanism for catagen induction in mouse skin.
authors.affiliation: Department of Biomedical Sciences, School of Medicine, Creighton University, Omaha, NE, USA.
authors.forename: Kyle J
authors.initials: KJ
authors.lastname: Bichsel
authors.affiliation: Department of Biomedical Sciences, School of Medicine, Creighton University, Omaha, NE, USA.
authors.forename: Brianna
authors.initials: B
authors.lastname: Hammiller
authors.affiliation: Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, USA.
authors.forename: Carol S
authors.initials: CS
authors.lastname: Trempus
authors.affiliation: Department of Biomedical Sciences, School of Medicine, Creighton University, Omaha, NE, USA.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Biomedical Sciences, School of Medicine, Creighton University, Omaha, NE, USA.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Hansen
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D018859:Hair Follicle / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism; D050777:Stathmin / Q000235:genetics / Q000378:metabolism*
chemical_list: D002868:Chromosomal Proteins, Non-Histone; C000613888:Rcc2 protein, mouse; D050777:Stathmin; C493994:Stmn1 protein, mouse; C541485:EGFR protein, mouse; D066246:ErbB Receptors
keywords: Rcc2; Stathmin 1; catagen; epidermal growth factor receptor; hair follicle cycling