| First Author | Barlow HR | Year | 2023 |
| Journal | Dev Biol | Volume | 499 |
| Pages | 59-74 | PubMed ID | 37172642 |
| Mgi Jnum | J:336187 | Mgi Id | MGI:7487895 |
| Doi | 10.1016/j.ydbio.2023.05.002 | Citation | Barlow HR, et al. (2023) Rab11 is essential to pancreas morphogenesis, lumen formation and endocrine mass. Dev Biol 499:59-74 |
| abstractText | The molecular links between tissue-level morphogenesis and the differentiation of cell lineages in the pancreas remain elusive despite a decade of studies. We previously showed that in pancreas both processes depend on proper lumenogenesis. The Rab GTPase Rab11 is essential for epithelial lumen formation in vitro, however few studies have addressed its functions in vivo and none have tested its requirement in pancreas. Here, we show that Rab11 is critical for proper pancreas development. Co-deletion of the Rab11 isoforms Rab11A and Rab11B in the developing pancreatic epithelium (Rab11(pancDKO)) results in approximately 50% neonatal lethality and surviving adult Rab11(pancDKO) mice exhibit defective endocrine function. Loss of both Rab11A and Rab11B in the embryonic pancreas results in morphogenetic defects of the epithelium, including defective lumen formation and lumen interconnection. In contrast to wildtype cells, Rab11(pancDKO) cells initiate the formation of multiple ectopic lumens, resulting in a failure to coordinate a single apical membrane initiation site (AMIS) between groups of cells. This results in an inability to form ducts with continuous lumens. Here, we show that these defects are due to failures in vesicle trafficking, as apical and junctional components remain trapped within Rab11(pancDKO) cells. Together, these observations suggest that Rab11 directly regulates epithelial lumen formation and morphogenesis. Our report links intracellular trafficking to organ morphogenesis in vivo and presents a novel framework for decoding pancreatic development. |
