How the nervous and digestive systems communicate
Surprising it may be to some that the vinegar or fruit fly, Drosophila melanogaster, has taught us more about ourselves than almost any other animal. Time has proven this small, simple creature to be an ideal genetic and developmental research model. But what can an animal smaller than a fingernail, and with a rigid exoskeleton that limits its growth tell us about the multitude of health issues associated with our seemingly ever-expanding appetites? A surprising amount according to Irene Miguel-Aliaga, who heads the latest scientific addition to the CSC, the Gut Signalling and Metabolism Group.
“We’re interested in how the brain and the gut talk to one another,” explains Miguel-Aliaga. “It’s becoming apparent that when they talk in the wrong way it can lead to metabolic disorders, diabetes or obesity. But it’s not clear what molecules are used in this communication, or how the crosstalk works.” With 500 million neurons in the mammalian gut, mapping the maze of communication using the Drosophila system as a starting point is relatively simple.
Miguel-Aliaga has been probing the relationship between brain and gut for some time, working at the University of Cambridge before coming to the CSC. “As a developmental neurobiologist, my first interest was the neurons themselves – how do they get there, what makes them target the gut, why are they different from other neurons?” As she reveals, the first step was to map the unknown territory, “We began with characterising the different neurons in Drosophila gut, mapping their anatomy to understand them better.”
As the work has progressed, the group’s interests have moved from the purely anatomical to the functional. The hunt for a deeper understanding now brings Miguel-Aliaga and her team to the CSC. “We’re hoping to collaborate with other groups within the CSC, and to explore the relevance of our findings in mammalian systems.”
Simultaneously approaching the system from several angles, and exploiting the fly’s genetic malleability, the group is starting to build up a full picture of how the gut influences metabolism. “One investigation is focussed on the neurons themselves: by visualising and manipulating the expression of specific genes, we can reveal the precise function of groups of neurons. Other team members are busy identifying nutrient sensors in the gut, to investigate how the activity of transporters or receptors affects fly nutrition. And a proportion of our effort is invested in characterising the signals that come out of the gut itself, looking at how the gut impacts other organs.”
Recent work has revealed that, despite the relative simplicity of the fly digestive tract compared to the human system, many of the fundamental roles in maintaining metabolic stability are conserved across the species. “The way fly gut responds to nutritional conditions is very similar to ours,” confirms Miguel-Aliaga. The significance of that is clear. Making sense of the Drosophila signal network could lead to the identification of appetite and metabolic regulators, which when applied to humans could seed new treatments for obesity and diabetes – two of the most significant contemporary health concerns.
Image: The digestive and reproductive systems of an adult female fly. Courtesy of Irene Miguel-Aliaga