Targeting of sensory axons in the olfactory bulb

PROJECT SUMMARY/ABSTRACT The objective of this proposal is to understand how the first elements of olfactory circuitry are correctly wired together during embryonic development. Odorant sensing neurons project axons from the olfactory epithelium to the olfactory bulb in the brain. Each olfactory sensory neuron in the epithelium chooses a single odorant receptor to express from a very large gene repertoire. Remarkably, all the sensory neurons that have chosen the same odorant receptor to express extend axons that converge together in specific reproducible locations within the olfactory bulb. This research proposal addresses how olfactory sensory axons locate their specific targets in the brain. This project takes advantage of the relative simplicity of the zebrafish olfactory system and its developmental and experimental accessibility to study the guidance of sensory neurons between the olfactory epithelium and the bulb. In the first Aim, single cell RNA sequencing is used to identify cell surface or secreted proteins that are differentially expressed between groups of olfactory sensory neurons whose axons target different and distinct regions in the olfactory bulb. These are candidate genes involved in targeting, and their function will be assessed by knocking them down one at a time and testing whether OSN axons target their correct locations in the olfactory bulb. In the second Aim, we will examine the role an important family of axon guidance cues, the slits, play in directing olfactory sensory axons to their appropriate target regions in the bulb. These studies build towards a systems level understanding of how an important functional circuit is assembled during development. This knowledge will be essential in the formulation of therapies for the regeneration and repair of olfactory circuitry in aging or anosmic patients.