Fibroblast Growth Factor Signaling Instructs Ensheathing Glia Wrapping of Drosophila Olfactory Glomeruli

Abstract

The formation of complex yet highly organized neural circuits requires interactions between neurons and glia. During the assembly of the Drosophila olfactory circuit, 50 olfactory receptor neuron (ORN) classes and 50 projection neuron (PN) classes form synaptic connections in 50 glomerular compartments in the antennal lobe, each of which represents a discrete olfactory information processing channel. Each compartment is separated from the adjacent compartments by membranous processes from ensheathing glia. Here we show that Thisbe, a fibroblast growth factor (FGF) released from olfactory neurons, particularly local interneurons, instructs ensheathing glia to wrap each glomerulus. The Heartless FGF receptor acts cell-autonomously in ensheathing glia to regulate process extension so as to insulate each neuropil compartment. Overexpressing Thisbe in ORNs or PNs causes over-wrapping of glomeruli to which their axons or dendrites target. Failure to establish the FGF-dependent glia structure disrupts precise ORN axon targeting and discrete glomerular formation.\n\nSignificance StatementThis research reports that reciprocal interactions between Drosophila olfactory neurons and ensheathing glia mediate the formation of neuronal compartments--groups of synapses that are packed into discrete structures called glomeruli that carry specific olfactory information. Ensheathing glia respond to a neuronal cue, the fibroblast growth factor (FGF) Thisbe, to pattern the boundaries of the nascent compartments. Neural compartments in turn require such glial barriers to separate themselves from neighboring compartments, so as to ensure the correct organization of the olfactory circuit. These findings highlight the importance of glia in the assembly and maintenance of neural circuits and the functions of FGF signaling in these processes.