Knock-down of ZBED6 in insulin-producing cells promotes N-cadherin junctions between beta-cells and neural crest stem cells in vitro

Wang, Xuan,1984-Uppsala universitet,Institutionen för medicinsk cellbiologi,Science for Life Laboratory, SciLifeLab (author)

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.

Xie, BeichenUppsala universitet,Institutionen för medicinsk cellbiologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)beixi713 (author)
Qi, YuUppsala universitet,Institutionen för medicinsk cellbiologi,Science for Life Laboratory, SciLifeLab (author)
Wallerman, OlaUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)olwal516 (author)
Vasylovska, SvitlanaUppsala universitet,Regenerativ neurobiologi(Swepub:uu)sviva947 (author)
Andersson, LeifUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)leand227 (author)
Kozlova, ElenaUppsala universitet,Regenerativ neurobiologi(Swepub:uu)elenkozl (author)
Welsh, NilsUppsala universitet,Institutionen för medicinsk cellbiologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)nilswels (author)
Uppsala universitetInstitutionen för medicinsk cellbiologi (creator_code:org_t)

By the author/editor: Wang, Xuan, 1984 ...; Xie, Beichen; Qi, Yu; Wallerman, Ola; Vasylovska, Svit ...; Andersson, Leif; show more...; Kozlova, Elena; Welsh, Nils; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Cell and Molecul ...

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