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| Item Type: | Article |
|---|---|
| Title: | Pancreatic exocrine tissue architecture and integrity are maintained by e-cadherin during postnatal development |
| Creators Name: | Serrill, J.D. and Sander, M. and Shih, H.P. |
| Abstract: | Cadherin-mediated cell-cell adhesion plays an important role in organ development and changes in cadherin expression are often linked to morphogenetic and pathogenic events. Cadherins interact with other intracellular components to form adherens junctions (AJs) and provide mechanical attachments between adjacent cells. E-cadherin (Cdh1) represents an integral component of these intercellular junctions. To elucidate the function of E-cadherin in the developing pancreas, we generated and studied pancreas-specific Cdh1-knockout (Cdh1(ΔPan/ΔPan)) mice. Cdh1(ΔPan/ΔPan) mice exhibit normal body size at birth, but fail to gain weight and become hypoglycemic soon afterward. We found that E-cadherin is not required for the establishment of apical-basal polarity or pancreatic exocrine cell identity at birth. However, four days after birth, the pancreata of Cdh1(ΔPan/ΔPan) mutants display progressive deterioration of exocrine architecture and dysregulation of Wnt and YAP signaling. At this time point, the acinar cells of Cdh1(ΔPan/ΔPan) mutants begin to exhibit ductal phenotypes, suggesting acinar-to-ductal metaplasia (ADM) in the E-cadherin-deficient pancreas. Our findings demonstrate that E-cadherin plays an integral role in the maintenance of exocrine architecture and regulation of homeostatic signaling. The present study provides insights into the involvement of cadherin-mediated cell-cell adhesion in pathogenic conditions such as pancreatitis or pancreatic cancer. |
| Keywords: | Signal Transducing Adaptor Proteins, Cadherins, Cell Adhesion, Cell Cycle Proteins, Knockout Mice, Exocrine Pancreas, Pancreatic Neoplasms, Pancreatitis, Phosphoproteins, Wnt Signaling Pathway, YAP-Signaling Proteins, Animals, Mice |
| Source: | Scientific Reports |
| ISSN: | 2045-2322 |
| Publisher: | Nature Publishing Group |
| Volume: | 8 |
| Number: | 1 |
| Page Range: | 13451 |
| Date: | 7 September 2018 |
| Official Publication: | https://doi.org/10.1038/s41598-018-31603-2 |
| PubMed: | View item in PubMed |
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