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. |