title: MicroRNA-214 controls skin and hair follicle development by modulating the activity of the Wnt pathway.
abstract: Skin development is governed by complex programs of gene activation and silencing, including microRNA-dependent modulation of gene expression. Here, we show that miR-214 regulates skin morphogenesis and hair follicle (HF) cycling by targeting β-catenin, a key component of the Wnt signaling pathway. miR-214 exhibits differential expression patterns in the skin epithelium, and its inducible overexpression in keratinocytes inhibited proliferation, which resulted in formation of fewer HFs with decreased hair bulb size and thinner hair production. The inhibitory effects of miR-214 on HF development and cycling were associated with altered activities of multiple signaling pathways, including decreased expression of key Wnt signaling mediators β-catenin and Lef-1, and were rescued by treatment with pharmacological Wnt activators. Finally, we identify β-catenin as one of the conserved miR-214 targets in keratinocytes. These data provide an important foundation for further analyses of miR-214 as a key regulator of Wnt pathway activity and stem cell functions during normal tissue homeostasis, regeneration, and aging.
authors.affiliation: Centre for Skin Sciences, School of Life Sciences, University of Bradford, Bradford BD7 1DP, England, UK.
authors.forename: Mohammed I
authors.initials: MI
authors.lastname: Ahmed
authors.affiliation: Centre for Skin Sciences, School of Life Sciences, University of Bradford, Bradford BD7 1DP, England, UK.
authors.forename: Majid
authors.initials: M
authors.lastname: Alam
authors.affiliation: Department of Dermatology, Boston University, Boston, MA 02118.
authors.forename: Vladimir U
authors.initials: VU
authors.lastname: Emelianov
authors.affiliation: Centre for Skin Sciences, School of Life Sciences, University of Bradford, Bradford BD7 1DP, England, UK.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Poterlowicz
authors.affiliation: Centre for Skin Sciences, School of Life Sciences, University of Bradford, Bradford BD7 1DP, England, UK.
authors.forename: Ankit
authors.initials: A
authors.lastname: Patel
authors.affiliation: Department of Dermatology, Boston University, Boston, MA 02118.
authors.forename: Andrey A
authors.initials: AA
authors.lastname: Sharov
authors.affiliation: Centre for Skin Sciences, School of Life Sciences, University of Bradford, Bradford BD7 1DP, England, UK.
authors.forename: Andrei N
authors.initials: AN
authors.lastname: Mardaryev
authors.affiliation: Centre for Skin Sciences, School of Life Sciences, University of Bradford, Bradford BD7 1DP, England, UK n.botchkareva@bradford.ac.uk.
authors.forename: Natalia V
authors.initials: NV
authors.lastname: Botchkareva
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics; D005838:Genotype; D018859:Hair Follicle / Q000254:growth & development* / Q000378:metabolism; D053550:Keratin-10 / Q000096:biosynthesis; D053547:Keratin-14 / Q000096:biosynthesis; D015603:Keratinocytes / Q000166:cytology; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000096:biosynthesis / Q000235:genetics*; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D012038:Regeneration / Q000235:genetics; D012867:Skin / Q000254:growth & development / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000096:biosynthesis / Q000235:genetics
chemical_list: D053547:Keratin-14; C507491:Krt10 protein, mouse; C507446:Krt14 protein, mouse; C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D008565:Membrane Proteins; D035683:MicroRNAs; C534781:Mirn214 microRNA, mouse; D051153:Wnt Proteins; D051176:beta Catenin; C064554:loricrin; D053550:Keratin-10