The shape of the olfactory bulb influences axon targeting

Each primary olfactory neuron in the mouse expresses a single type of odorant receptor. All neurons expressing the same odorant receptor gene typically project to two topographically fixed glomeruli, one each on the medial and lateral surfaces of the olfactory bulb. While topographic gradients of guidance receptors and their ligands help to establish the retinotectal projection, similar orthogonal distributions of cues have not yet been detected within the olfactory system. While odorant receptors are crucial for the final targeting of axons to glomeruli, it is unclear whether the olfactory bulb itself provides instructive cues for the establishment of the topographic map. To begin to understand the role of the olfactory bulb in the formation of the olfactory nerve pathway, we developed a model whereby the gross shape of the bulb in the P2-IRES-tau-LacZ line of mice was radically altered during postnatal development. We have shown here that the topography of axons expressing the P2 odorant receptor is dependent on the shape of the olfactory bulb. When the dorsoventral axis of the olfactory bulb was compressed during the early postnatal period, newly developing P2 axons projected to multiple inappropriate glomeruli surrounding their normal target site. These results suggest that the distribution of local guidance cues within the olfactory bulb is influenced by the shape of the olfactory bulb and that these cues contribute to the topographic positioning of glomeruli.