| First Author | Adams MT | Year | 2018 |
| Journal | Sci Rep | Volume | 8 |
| Issue | 1 | Pages | 10876 |
| PubMed ID | 30022126 | Mgi Jnum | J:268735 |
| Mgi Id | MGI:6271921 | Doi | 10.1038/s41598-018-29118-x |
| Citation | Adams MT, et al. (2018) Endocrine cell type sorting and mature architecture in the islets of Langerhans require expression of Roundabout receptors in beta cells. Sci Rep 8(1):10876 |
| abstractText | Pancreatic islets of Langerhans display characteristic spatial architecture of their endocrine cell types. This architecture is critical for cell-cell communication and coordinated hormone secretion. Islet architecture is disrupted in type-2 diabetes. Moreover, the generation of architecturally correct islets in vitro remains a challenge in regenerative approaches to type-1 diabetes. Although the characteristic islet architecture is well documented, the mechanisms controlling its formation remain obscure. Here, we report that correct endocrine cell type sorting and the formation of mature islet architecture require the expression of Roundabout (Robo) receptors in beta cells. Mice with whole-body deletion of Robo1 and conditional deletion of Robo2 either in all endocrine cells or selectively in beta cells show complete loss of endocrine cell type sorting, highlighting the importance of beta cells as the primary organizer of islet architecture. Conditional deletion of Robo in mature beta cells subsequent to islet formation results in a similar phenotype. Finally, we provide evidence to suggest that the loss of islet architecture in Robo KO mice is not due to beta cell transdifferentiation, cell death or loss of beta cell differentiation or maturation. |
