Dr. Alvaro Banderas

The gut microbiota, immune system, and enteric nervous system interact to regulate adult gut physiology. However, the mechanisms establishing gut physiology during development remain unknown. We report that in developing zebrafish, enteroendocrine cells produced interleukin-22 (IL-22) in response to microbial signals before lymphocytes populated the gut. In larvae, IL-22 shaped the gut microbiota, increasing Lactobacillaceae abundance and ghrelin expression to promote gut motility. Impaired motility and ghrelin expression were restored in il22−/− zebrafish by transfer of microbiota from wild-type zebrafish or by introducing only Lactobacillus plantarum. IL-22–deficient mice also had impaired gut motility and reduced ghrelin expression in early life, indicating a conserved function. Thus, before immune system maturation, enteroendocrine cells regulate early-life gut function by controlling the microbiota through IL-22.

During mating in budding yeast, cells use pheromones to locate each other and fuse. This model system has shaped our current understanding of signal transduction and cell polarization in response to extracellular signals. The cell populations producing extracellular signal landscapes themselves are, however, less well understood, yet crucial for functionally testing quantitative models of cell polarization and for controlling cell behavior through bioengineering approaches. Here we engineered optogenetic control of pheromone landscapes in mating populations of budding yeast, hijacking the mating-pheromone pathway to achieve spatial control of growth, cell morphology, cell-cell fusion, and distance-dependent gene expression in response to light. Using our tool, we were able to spatially control and shape pheromone gradients, allowing the use of a biophysical model to infer the properties of large-scale gradients generated by mating populations in a single, quantitative experimental setup, predicting that the shape of such gradients depends quantitatively on population parameters. Spatial optogenetic control of diffusible signals and their degradation provides a controllable signaling environment for engineering artificial communication and cell-fate systems in gel-embedded cell populations without the need for physical manipulation.