Gut-innervating neurons: investigating effects on organ physiology and neuronal diversity

Abstract

Bidirectional communication between the brain and the gut is extensive and physiologically significant. The density and significance of innervation emanating from the central nervous system (CNS) vary along the length of the gastrointestinal tract, and may be particularly prominent in the mammalian stomach. In this thesis, I have explored enteric innervation in Drosophila melanogaster, taking advantage of its relative simplicity and genetic tractability. In particular, I have investigated the anatomy, function and/or intrinsic metabolic state of distinct subsets of peptidergic enteric neurons. I have first focused on neurons that innervate the crop: a stomach-like portion of the adult gut. I have characterised the anatomy of genetically defined neuropeptidergic Myosuppressin (Ms)-expressing neurons, and found Ms neuronal subsets in the brains pars intercerebralis and the peripheral hypocerebral ganglion that innervate the crop. I have investigated the expression of candidate Ms receptors and found that the Ms receptor MsR1 is expressed in the crop muscles and in central and peripheral neurons. I have developed assays to monitor crop filling, which I have combined with genetic manipulations to affect the activity of the Ms neurons, their Ms expression or that of its receptor. I have found that Ms signalling is required for crop filling acting through its receptor in crop muscles. Unexpectedly, this requirement was only apparent in female flies post mating. Furthermore, I found that crop filling/emptying affects food intake, revealing a novel role for this relatively unexplored organ. In addition, I have used another subset of enteric neurons – the Ilp7 neurons - to test the hypothesis that differences in the metabolic state of neurons may contribute to neuronal diversification by differentially supporting axonal extension. However, an RNAi screen that targeted key metabolic regulators failed to provide support for this hypothesis.