Desmoglein 4 in hair follicle differentiation and epidermal adhesion: Evidence from inherited hypotrichosis and acquired pemphigus vulgaris

Ana Kljuic, Hisham Bazzi, John P. Sundberg, Amalia Martinez-Mir, Ryan O'Shaughnessy, My G. Mahoney, Moise Levy, Xavier Montagutelli, Wasim Ahmad, Vincent M. Aita, Derek Gordon, Jouni Uitto, David Whiting, Jurg Ott, Stuart Fischer, T. Conrad Gilliam, Colin A B Jahoda, Rebecca J. Morris, Andrei A. Panteleyev, Vu Thuong NguyenAngela M. Christiano

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251 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)249-260
Number of pages12
JournalCell
Volume113
Issue number2
DOIs
StatePublished - Apr 18 2003

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    Kljuic, A., Bazzi, H., Sundberg, J. P., Martinez-Mir, A., O'Shaughnessy, R., Mahoney, M. G., Levy, M., Montagutelli, X., Ahmad, W., Aita, V. M., Gordon, D., Uitto, J., Whiting, D., Ott, J., Fischer, S., Gilliam, T. C., Jahoda, C. A. B., Morris, R. J., Panteleyev, A. A., ... Christiano, A. M. (2003). Desmoglein 4 in hair follicle differentiation and epidermal adhesion: Evidence from inherited hypotrichosis and acquired pemphigus vulgaris. Cell, 113(2), 249-260. https://doi.org/10.1016/S0092-8674(03)00273-3