title: The tight-junction protein claudin-6 induces epithelial differentiation from mouse F9 and embryonic stem cells.
abstract: During epithelialization, cell adhesions and polarity must be established to maintain tissue assemblies and separate the biological compartments in the body. However, the molecular basis of epithelial morphogenesis, in particular, a role of cell adhesion molecules in epithelial differentiation from stem cells, remains unclear. Here, we show that the stable and conditional expression of a tight-junction protein, claudin-6 (Cldn6), triggers epithelial morphogenesis in mouse F9 stem cells. We also demonstrate that Cldn6 induces the expression of other tight-junction and microvillus molecules including Cldn7, occludin, ZO-1α+, and ezrin/radixin/moesin-binding phosphoprotein50. These events were inhibited by attenuation of Cldn6 using RNA interference or the C-terminal half of Clostridium Perfringens enterotoxin. Furthermore, similar results were obtained in mouse embryonic stem cells. Thus, we have uncovered that the Cldn6 functions as a novel cue to induce epithelial differentiation.
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Naoki
authors.initials: N
authors.lastname: Ichikawa-Tomikawa
authors.forename: Seiro
authors.initials: S
authors.lastname: Satohisa
authors.forename: Yushi
authors.initials: Y
authors.lastname: Akashi
authors.forename: Risa
authors.initials: R
authors.lastname: Kanai
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Saito
authors.forename: Norimasa
authors.initials: N
authors.lastname: Sawada
authors.forename: Hideki
authors.initials: H
authors.lastname: Chiba
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D057167:Claudins / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D062793:Occludin / Q000235:genetics / Q000378:metabolism; D062826:Zonula Occludens-1 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D057167:Claudins; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D062793:Occludin; D062826:Zonula Occludens-1 Protein; C071776:radixin; C122101:claudin 6