RRC ID 47247
Author Zapiec B, Bressel OC, Khan M, Walz A, Mombaerts P.
Title Neuropilin-1 and the Positions of Glomeruli in the Mouse Olfactory Bulb.
Journal eNeuro
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 conditional Nrp1 knockout. 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 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.
Volume 3(5)
Published 2016-9
DOI 10.1523/ENEURO.0123-16.2016
PII eN-NWR-0123-16
PMID 27844052
PMC PMC5089123
MeSH Animals Axons / metabolism Cyclic AMP / metabolism Female Imaging, Three-Dimensional Immunohistochemistry Male Mice, Inbred C57BL Mice, Transgenic Microscopy, Confocal Neuropilin-1 / genetics Neuropilin-1 / metabolism* Olfactory Bulb / cytology Olfactory Bulb / metabolism* Olfactory Receptor Neurons / cytology Olfactory Receptor Neurons / metabolism* Rats Receptors, Odorant / genetics Receptors, Odorant / metabolism Tomography
Resource
Mice C57BL/6-Tg(Olfr16-Olr226 -Cre -EYFP)1Hsak(RBRC02932)