View Program - 63rd Annual Drosophila Research Conference

The last few years have witnessed an increased interest in the gastrointestinal tract beyond stem cell research. This is especially true for enteroendocrine (EE) cells, a secretory lineage from intestinal stem cells (ISCs) that plays a key role in sensing local and external stimuli, which are translated into major physiological outputs. As in vertebrates, Drosophila has a diverse EE system scattered along the midgut epithelium and organized into subpopulations of cells expressing different neuroendocrine (NE) peptides. EE cells and NE peptides alterations are recognized features of intestinal damage and gastrointestinal pathologies, such as inflammatory bowel diseases (IBD). However, the functional significance of EE cell disruptions in intestinal physiopathology remains poorly understood. Here, we used adult Drosophila melanogaster as an in vivo model organism to study EE cells function and the functional implications of EE cell disruptions in intestinal damage and inflammation. Previous studies have shown the importance of EE cells to maintain intestinal homeostasis. Depletion of EE cells has a strong impact on intestinal regeneration. On the other hand, we have observed that long-term damage or inflammation favors the increase of EE cell proportion and ectopic expression of NE peptides. To unravel the functional significance of this phenomenon, we performed a genetic screen to identify gut-derived NE peptides that impact ISC proliferation. Our results suggest a novel role for the EE peptide DH31 in this context. DH31 expression in the adult midgut is upregulated upon intestinal damage by feeding with the bacteria Pseudomonas entomophila or chemical treatment with ROS, resulting in previously unrecognized signaling to midgut-associated tissues and regulation of ISC niche factors to support intestinal regeneration.

Enteroendocrine control of intestinal health and disease in Drosophila