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Publication : Cadherins regulate aggregation of pancreatic beta-cells in vivo.

First Author  Dahl U Year  1996
Journal  Development Volume  122
Issue  9 Pages  2895-902
PubMed ID  8787762 Mgi Jnum  J:35810
Mgi Id  MGI:83254 Doi  10.1242/dev.122.9.2895
Citation  Dahl U, et al. (1996) Cadherins regulate aggregation of pancreatic beta-cells in vivo. Development 122(9):2895-902
abstractText  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.
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