title: CD133 expression correlates with membrane beta-catenin and E-cadherin loss from human hair follicle placodes during morphogenesis.
abstract: Genetic studies suggest that the major events of human hair follicle development are similar to those in mice, but detailed analyses of this process are lacking. In mice, hair follicle placode "budding" is initiated by invagination of Wnt-induced epithelium into the underlying mesenchyme. Modification of adherens junctions (AJs) is clearly required for budding. Snail-mediated downregulation of AJ component E-cadherin is important for placode budding in mice. Beta-catenin, another AJ component, has been more difficult to study owing to its essential functions in Wnt signaling, a prerequisite for hair follicle placode induction. Here, we show that a subset of human invaginating hair placode cells expresses the stem cell marker CD133 during early morphogenesis. CD133 associates with membrane beta-catenin in early placodes, and its continued expression correlates with loss of beta-catenin and E-cadherin from the cell membrane at a time when E-cadherin transcriptional repressors Snail and Slug are not implicated. Stabilization of CD133 via anti-CD133 antibody treatment of human fetal scalp explants depresses beta-catenin and E-cadherin membrane localization. We discuss this unique correlation and suggest a hypothetical model whereby CD133 promotes morphogenesis in early hair follicle placodes through the localized removal of membrane beta-catenin proteins and subsequent AJ dissolution.
authors.affiliation: Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Denise L
authors.initials: DL
authors.lastname: Gay
authors.affiliation: Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Dermatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Chao-Chun
authors.initials: CC
authors.lastname: Yang
authors.affiliation: Department of Developmental and Cell Biology, Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, California, USA.
authors.forename: Maksim V
authors.initials: MV
authors.lastname: Plikus
authors.affiliation: Department of Dermatology, New York University Langone Medical Center, New York, New York, USA.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Ito
authors.affiliation: Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Rivera
authors.affiliation: Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Elsa
authors.initials: E
authors.lastname: Treffeisen
authors.affiliation: Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Doherty
authors.affiliation: Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Spata
authors.affiliation: Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Millar
authors.affiliation: Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. Electronic address: cotsarel@mail.med.upenn.edu.
authors.forename: George
authors.initials: G
authors.lastname: Cotsarelis
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D055879:Gene Knock-In Techniques; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D018859:Hair Follicle / Q000166:cytology* / Q000254:growth & development / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008817:Mice, Mutant Strains; D009024:Morphogenesis / Q000502:physiology; D010455:Peptides / Q000235:genetics* / Q000378:metabolism; D012535:Scalp / Q000166:cytology; D059467:Transcriptome; D060449:Wnt Signaling Pathway / Q000502:physiology; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; C513384:CDH1 protein, human; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D015820:Cadherins; D006023:Glycoproteins; D008565:Membrane Proteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D051176:beta Catenin