title: Neuropilin-1 and the Positions of Glomeruli in the Mouse Olfactory Bulb.
abstract: It is 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 tested the model for the well-characterized mouse OR M71 using our gene-targeted mouse strains, which are publicly available. In contradiction to the model, we observed a variety of configurations for the M71 glomeruli in the conditionalNrp1knockout. We then reassessed the model for the original OR transgene with which the model was developed, using the same publicly available mouse strains. We discovered that glomerular positions do not undergo the simple anterior shift that has been reported in the conditionalNrp1knockout 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.
authors.affiliation: Max Planck Research Unit for Neurogenetics , 60438 Frankfurt, Germany.
authors.forename: Bolek
authors.initials: B
authors.lastname: Zapiec
authors.affiliation: Max Planck Research Unit for Neurogenetics , 60438 Frankfurt, Germany.
authors.forename: Olaf Christian
authors.initials: OC
authors.lastname: Bressel
authors.affiliation: Max Planck Research Unit for Neurogenetics , 60438 Frankfurt, Germany.
authors.forename: Mona
authors.initials: M
authors.lastname: Khan
authors.affiliation: Max Planck Research Unit for Neurogenetics , 60438 Frankfurt, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Walz
authors.affiliation: Max Planck Research Unit for Neurogenetics , 60438 Frankfurt, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Mombaerts
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D021621:Imaging, Three-Dimensional; D007150:Immunohistochemistry; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D039942:Neuropilin-1 / Q000235:genetics / Q000378:metabolism*; D009830:Olfactory Bulb / Q000166:cytology / Q000378:metabolism*; D018034:Olfactory Receptor Neurons / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D018035:Receptors, Odorant / Q000235:genetics / Q000378:metabolism; D014054:Tomography
chemical_list: C502656:Olfr151 protein, mouse; D018035:Receptors, Odorant; D039942:Neuropilin-1; D000242:Cyclic AMP
keywords: axon guidance; bulb; cAMP; neuropilin; odorant; olfactory