| First Author | Tixi W | Year | 2023 |
| Journal | Elife | Volume | 12 |
| PubMed ID | 37610090 | Mgi Jnum | J:348298 |
| Mgi Id | MGI:7640249 | Doi | 10.7554/eLife.90006 |
| Citation | Tixi W, et al. (2023) Coordination between ECM and cell-cell adhesion regulates the development of islet aggregation, architecture, and functional maturation. Elife 12 |
| abstractText | Pancreatic islets are three-dimensional cell aggregates consisting of unique cellular composition, cell-to-cell contacts, and interactions with blood vessels. Cell aggregation is essential for islet endocrine function; however, it remains unclear how developing islets establish aggregation. By combining genetic animal models, imaging tools, and gene expression profiling, we demonstrate that islet aggregation is regulated by extracellular matrix signaling and cell-cell adhesion. Islet endocrine cell-specific inactivation of extracellular matrix receptor integrin beta1 disrupted blood vessel interactions but promoted cell-cell adhesion and the formation of larger islets. In contrast, ablation of cell-cell adhesion molecule alpha-catenin promoted blood vessel interactions yet compromised islet clustering. Simultaneous removal of integrin beta1 and alpha-catenin disrupts islet aggregation and the endocrine cell maturation process, demonstrating that establishment of islet aggregates is essential for functional maturation. Our study provides new insights into understanding the fundamental self-organizing mechanism for islet aggregation, architecture, and functional maturation. |
