It has been known since 1996 that mouse odorant receptors (ORs) are involved in determining the positions of the sites of coalescence of axons of olfactory sensory neurons (OSNs) - the thousands of glomeruli in the olfactory bulb. But the molecular and cellular mechanisms of OR-mediated axonal coalescence into glomeruli remain unclear. A model was proposed in 2006-2009 whereby OR-derived cAMP signals, rather than direct action of OR molecules, determine the target destinations (glomeruli) of OSNs in the bulb. This model hypothesizes that OR-derived cAMP signals determine the expression levels of neuropilin-1 (Nrp1) in OSN axon termini; that levels of Nrp1 in glomeruli form a gradient from anterior-low to posterior-high throughout the bulb; and that these Nrp1 levels mechanistically determine anterior-posterior patterning of glomeruli. Here, we describe the first independent evaluation of the Nrp1 model since it was formulated a decade ago. We test this model for the well-characterized mouse OR M71 using our gene-targeted mouse strains, which are publicly available. In contradiction to this model, we observe a variety of configurations for the M71 glomeruli in the conditional Nrp1 knockout. We then reassess this model for the original OR transgene with which the model was developed, using the same, publicly available mouse strains. We discover that glomerular positions do not undergo the simple anterior shift that has been reported in the conditional Nrp1 knockout for this OR transgene. Taken together, our findings do not support the Nrp1 model for the anterior-posterior patterning of glomerular positions in the olfactory bulb.
Significance Statement: In the mouse, each olfactory sensory neuron expresses one of ∼1,100 odorant receptor genes. The odorant receptor determines to which odorants the neuron responds physiologically, and in which glomerulus of the olfactory bulb its axon terminates. A model was proposed 10 years ago whereby intracellular signals derived from the odorant receptor determine the level of neuropilin-1, which in turn determines the position of the glomerulus along the anterior-posterior axis of the bulb. We provide the first test of this model, for a well-characterized odorant receptor and separately with the original mouse strains that led to the formulation of the model. Our results do not support the neuropilin-1 model of anterior-posterior patterning of glomerular positions in the olfactory bulb.
Authors report no conflict of interest.
Max Planck Society.