title: Desmoglein 4 in hair follicle differentiation and epidermal adhesion: evidence from inherited hypotrichosis and acquired pemphigus vulgaris.
abstract: Cell adhesion and communication are interdependent aspects of cell behavior that are critical for morphogenesis and tissue architecture. In the skin, epidermal adhesion is mediated in part by specialized cell-cell junctions known as desmosomes, which are characterized by the presence of desmosomal cadherins, known as desmogleins and desmocollins. We identified a cadherin family member, desmoglein 4, which is expressed in the suprabasal epidermis and hair follicle. The essential role of desmoglein 4 in skin was established by identifying mutations in families with inherited hypotrichosis, as well as in the lanceolate hair mouse. We also show that DSG4 is an autoantigen in pemphigus vulgaris. Characterization of the phenotype of naturally occurring mutant mice revealed disruption of desmosomal adhesion and perturbations in keratinocyte behavior. We provide evidence that desmoglein 4 is a key mediator of keratinocyte cell adhesion in the hair follicle, where it coordinates the transition from proliferation to differentiation.
authors.affiliation: Department of Genetics and Development, Columbia University, New York, NY 10032, USA.
authors.forename: Ana
authors.initials: A
authors.lastname: Kljuic
authors.forename: Hisham
authors.initials: H
authors.lastname: Bazzi
authors.forename: John P
authors.initials: JP
authors.lastname: Sundberg
authors.forename: Amalia
authors.initials: A
authors.lastname: Martinez-Mir
authors.forename: Ryan
authors.initials: R
authors.lastname: O'Shaughnessy
authors.forename: My G
authors.initials: MG
authors.lastname: Mahoney
authors.forename: Moise
authors.initials: M
authors.lastname: Levy
authors.forename: Xavier
authors.initials: X
authors.lastname: Montagutelli
authors.forename: Wasim
authors.initials: W
authors.lastname: Ahmad
authors.forename: Vincent M
authors.initials: VM
authors.lastname: Aita
authors.forename: Derek
authors.initials: D
authors.lastname: Gordon
authors.forename: Jouni
authors.initials: J
authors.lastname: Uitto
authors.forename: David
authors.initials: D
authors.lastname: Whiting
authors.forename: Jurg
authors.initials: J
authors.lastname: Ott
authors.forename: Stuart
authors.initials: S
authors.lastname: Fischer
authors.forename: T Conrad
authors.initials: TC
authors.lastname: Gilliam
authors.forename: Colin A B
authors.initials: CA
authors.lastname: Jahoda
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Morris
authors.forename: Andrei A
authors.initials: AA
authors.lastname: Panteleyev
authors.forename: Vu Thuong
authors.initials: VT
authors.lastname: Nguyen
authors.forename: Angela M
authors.initials: AM
authors.lastname: Christiano
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002448:Cell Adhesion / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics*; D002874:Chromosome Mapping; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004252:DNA Mutational Analysis; D051182:Desmogleins; D004817:Epidermis / Q000196:embryology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D018859:Hair Follicle / Q000196:embryology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006983:Hypertrichosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D010392:Pemphigus / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D010641:Phenotype
chemical_list: D015820:Cadherins; D003598:Cytoskeletal Proteins; C473409:DSG4 protein, human; D051182:Desmogleins