title: Cadherins regulate aggregation of pancreatic beta-cells in vivo.
abstract: It is thought that the cadherin protein family of cell adhesion molecules regulates morphogenetic events in multicellular organisms. In this study we have investigated the importance of beta-cell cadherins for cell-cell interactions mediating the organization of endocrine cells into pancreatic islets of Langerhans. To interfere with endogenous cadherin activity in beta-cells during pancreatic development, we overexpressed a dominant negative mutant of mouse E-cadherin, lacking nearly all extracellular amino acids, in pancreatic beta-cells in transgenic mice. Expression of the truncated E-cadherin receptor displaced both E- and N-cadherin from pancreatic beta-cells. As a result, the initial clustering of beta-cells, which normally begins at 13.5-14.5 days postcoitum, was perturbed. Consequently, the clustering of endocrine cells into islets, which normally begins at 17.5-18 days postcoitum, was abrogated. Instead, transgenic beta-cells were found dispersed in the tissue as individual cells, while alpha-cells selectively aggregated into islet-like clusters devoid of beta-cells. Furthermore, expression of truncated E-cadherin in beta-cells resulted in an accumulation of beta-catenin in the cytoplasm. Thus, we have for the first time shown in vivo that cadherins regulate adhesive properties of beta-cells which are essential for the aggregation of endocrine cells into islets.
authors.affiliation: Department of Microbiology, University of Umeå, Sweden.
authors.forename: U
authors.initials: U
authors.lastname: Dahl
authors.forename: A
authors.initials: A
authors.lastname: Sjødin
authors.forename: H
authors.initials: H
authors.lastname: Semb
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000502:physiology*; D002448:Cell Adhesion; D002449:Cell Aggregation; D002465:Cell Movement; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental; D015151:Immunoblotting; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000166:cytology* / Q000196:embryology / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis; D009154:Mutation; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017384:Sequence Deletion; D015534:Trans-Activators; D051176:beta Catenin
chemical_list: C495267:CTNNB1 protein, mouse; D015820:Cadherins; D003598:Cytoskeletal Proteins; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D051176:beta Catenin