title: Cytoplasmic plaque formation in hemidesmosome development is dependent on SoxF transcription factor function.
abstract: Hemidesmosomes are composed of intricate networks of proteins, that are an essential attachment apparatus for the integrity of epithelial tissue. Disruption leads to blistering diseases such as epidermolysis bullosa. Members of the Sox gene family show dynamic and diverse expression patterns during development and mutation analyses in humans and mice provide evidence that they play a remarkable variety of roles in development and human disease. Previous studies have established that the mouse mutant ragged-opossum (Ra(op)) expresses a dominant-negative form of the SOX18 transcription factor that interferes with the function of wild type SOX18 and of the related SOXF-subgroup proteins SOX7 and -17. Here we show that skin and oral mucosa in homozygous Ra(op) mice display extensive detachment of epithelium from the underlying mesenchymal tissue, caused by tearing of epithelial cells just above the plasma membrane due to hemidesmosome disruption. In addition, several hemidesmosome proteins expression were found to be dysregulated in the Ra(op) mice. Our data suggest that SOXF transcription factors play a role in regulating formation of cytoplasmic plaque protein assembly, and that disrupted SOXF function results in epidermolysis bullosa-like skin phenotypes.
authors.affiliation: Craniofacial Development and Stem Cell Biology, and Biomedical Research Centre, Dental Institute, King's College London, London, United Kingdom.
authors.forename: Shelly
authors.initials: S
authors.lastname: Oommen
authors.forename: Mathias
authors.initials: M
authors.lastname: Francois
authors.forename: Maiko
authors.initials: M
authors.lastname: Kawasaki
authors.forename: Melanie
authors.initials: M
authors.lastname: Murrell
authors.forename: Katsushige
authors.initials: K
authors.lastname: Kawasaki
authors.forename: Thantrira
authors.initials: T
authors.lastname: Porntaveetus
authors.forename: Sarah
authors.initials: S
authors.lastname: Ghafoor
authors.forename: Neville J
authors.initials: NJ
authors.lastname: Young
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Okamatsu
authors.forename: John
authors.initials: J
authors.lastname: McGrath
authors.forename: Peter
authors.initials: P
authors.lastname: Koopman
authors.forename: Paul T
authors.initials: PT
authors.lastname: Sharpe
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ohazama
mesh_terms: D000818:Animals; D003593:Cytoplasm / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004820:Epidermolysis Bullosa / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D024002:HMGB Proteins / Q000235:genetics / Q000378:metabolism; D022002:Hemidesmosomes / Q000378:metabolism* / Q000473:pathology; D006720:Homozygote; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009061:Mouth Mucosa / Q000378:metabolism* / Q000473:pathology; D009154:Mutation; D010641:Phenotype; D055760:SOXF Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism* / Q000473:pathology
chemical_list: D024002:HMGB Proteins; D055760:SOXF Transcription Factors; C511606:Sox17 protein, mouse; C490653:Sox18 protein, mouse; C102515:Sox7 protein, mouse