title: Knock-down of ZBED6 in insulin-producing cells promotes N-cadherin junctions between beta-cells and neural crest stem cells in vitro.
abstract: The role of the novel transcription factor ZBED6 for the adhesion/clustering of insulin-producing mouse MIN6 and βTC6 cells was investigated. Zbed6-silencing in the insulin producing cells resulted in increased three-dimensional cell-cell clustering and decreased adhesion to mouse laminin and human laminin 511. This was paralleled by a weaker focal adhesion kinase phosphorylation at laminin binding sites. Zbed6-silenced cells expressed less E-cadherin and more N-cadherin at cell-to-cell junctions. A strong ZBED6-binding site close to the N-cadherin gene transcription start site was observed. Three-dimensional clustering in Zbed6-silenced cells was prevented by an N-cadherin neutralizing antibody and by N-cadherin knockdown. Co-culture of neural crest stem cells (NCSCs) with Zbed6-silenced cells, but not with control cells, stimulated the outgrowth of NCSC processes. The cell-to-cell junctions between NCSCs and βTC6 cells stained more intensely for N-cadherin when Zbed6-silenced cells were co-cultured with NCSCs. We conclude that ZBED6 decreases the ratio between N- and E-cadherin. A lower N- to E-cadherin ratio may hamper the formation of three-dimensional beta-cell clusters and cell-to-cell junctions with NCSC, and instead promote efficient attachment to a laminin support and monolayer growth. Thus, by controlling beta-cell adhesion and cell-to-cell junctions, ZBED6 might play an important role in beta-cell differentiation, proliferation and survival.
authors.affiliation: Science for Life Laboratory, Department of Medical Cell Biology, Uppsala University, 751 23 Uppsala, Sweden.
authors.forename: Xuan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Science for Life Laboratory, Department of Medical Cell Biology, Uppsala University, 751 23 Uppsala, Sweden.
authors.forename: Beichen
authors.initials: B
authors.lastname: Xie
authors.affiliation: Science for Life Laboratory, Department of Medical Cell Biology, Uppsala University, 751 23 Uppsala, Sweden.
authors.forename: Yu
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, 751 23 Uppsala, Sweden.
authors.forename: Ola
authors.initials: O
authors.lastname: Wallerman
authors.affiliation: Department of Neuroscience, Uppsala University, 751 23 Uppsala, Sweden.
authors.forename: Svitlana
authors.initials: S
authors.lastname: Vasylovska
authors.affiliation: Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, 751 23 Uppsala, Sweden.
authors.forename: Leif
authors.initials: L
authors.lastname: Andersson
authors.affiliation: Department of Neuroscience, Uppsala University, 751 23 Uppsala, Sweden.
authors.forename: Elena Nickolaevna
authors.initials: EN
authors.lastname: Kozlova
authors.affiliation: Science for Life Laboratory, Department of Medical Cell Biology, Uppsala University, 751 23 Uppsala, Sweden.
authors.forename: Nils
authors.initials: N
authors.lastname: Welsh
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D002448:Cell Adhesion; D049109:Cell Proliferation; D018920:Coculture Techniques; D005786:Gene Expression Regulation; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D007365:Intercellular Junctions / Q000378:metabolism* / Q000648:ultrastructure; D007797:Laminin / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009432:Neural Crest / Q000166:cytology / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D015820:Cadherins; C000611838:Cdh1 protein, mouse; C489083:Cdh2 protein, mouse; D007797:Laminin; D034741:RNA, Small Interfering; D012097:Repressor Proteins; C547913:ZBED6 protein, mouse