title: Alteration of Nrp1 signaling at different stages of olfactory neuron maturation promotes glomerular shifts along distinct axes in the olfactory bulb.
abstract: Building the topographic map in the mammalian olfactory bulb is explained by a model based on two axes along which sensory neurons are guided: one dorsoventral and one anteroposterior. This latter axis relies on specific expression levels of Nrp1. To evaluate the role of this receptor in this process, we used an in vivo genetic approach to decrease or suppress Nrp1 in specific neuronal populations and at different time points during axonal targeting. We observed, in neurons that express the M71 or M72 odorant receptors, that Nrp1 inactivation leads to two distinct wiring alterations, depending on the time at which Nrp1 expression is altered: first, a surprising dorsal shift of the M71 and M72 glomeruli, which often fuse with their contralateral counterparts, and second the formation of anteriorized glomeruli. The two phenotypes are partly recapitulated in mice lacking the Nrp1 ligand Sema3A and in mice whose sensory neurons express an Nrp1 mutant unable to bind Sema3A. Using a mosaic conditional approach, we show that M71 axonal fibers can bypass the Nrp1 signals that define their target area, since they are hijacked and coalesce with Nrp1-deficient M71-expressing axons that target elsewhere. Together, these findings show drastically different axonal targeting outcomes dependent on the timing at which Nrp1/Sema3A signaling is altered.
authors: Department of Genetics and Evolution, University of Geneva, Geneva 1205, Switzerland.|Geneva Neuroscience Center, University of Geneva, Geneva 1205, Switzerland.
authors: Alexis
authors: A
authors: Assens
authors: Department of Genetics and Evolution, University of Geneva, Geneva 1205, Switzerland.|Geneva Neuroscience Center, University of Geneva, Geneva 1205, Switzerland.
authors: Julien A
authors: JA
authors: Dal Col
authors: Department of Genetics and Evolution, University of Geneva, Geneva 1205, Switzerland.|Geneva Neuroscience Center, University of Geneva, Geneva 1205, Switzerland.
authors: Anthony
authors: A
authors: Njoku
authors: Department of Genetics and Evolution, University of Geneva, Geneva 1205, Switzerland.|Geneva Neuroscience Center, University of Geneva, Geneva 1205, Switzerland.
authors: Quentin
authors: Q
authors: Dietschi
authors: Department of Genetics and Evolution, University of Geneva, Geneva 1205, Switzerland.|Geneva Neuroscience Center, University of Geneva, Geneva 1205, Switzerland.
authors: Chenda
authors: C
authors: Kan
authors: Department of Biological Sciences, Hunter College and The Graduate Center Biochemistry, Biology and Biopsychology and Behavioral Neuroscience Programs, CUNY, New York, NY10065, USA.
authors: Paul
authors: P
authors: Feinstein
authors: Geneva Neuroscience Center, University of Geneva, Geneva 1205, Switzerland alan.carleton@unige.ch ivan.rodriguez@unige.ch.|Department of Basic Neurosciences, School of Medicine, University of Geneva, Geneva 1205, Switzerland.
authors: Alan
authors: A
authors: Carleton
authors: Department of Genetics and Evolution, University of Geneva, Geneva 1205, Switzerland alan.carleton@unige.ch ivan.rodriguez@unige.ch.|Geneva Neuroscience Center, University of Geneva, Geneva 1205, Switzerland.
authors: Ivan
authors: 0000-0002-6468-0565
authors: I
authors: Rodriguez
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D007150:Immunohistochemistry; D051379:Mice; D039942:Neuropilin-1 / Q000235:genetics / Q000378:metabolism*; D009830:Olfactory Bulb / Q000166:cytology* / Q000196:embryology / Q000378:metabolism*; D018034:Olfactory Receptor Neurons / Q000166:cytology / Q000378:metabolism; D040121:Semaphorin-3A / Q000235:genetics / Q000378:metabolism
chemical_list: D040121:Semaphorin-3A; D039942:Neuropilin-1
keywords: Axon guidance; Mouse; Neuropilin 1; Olfaction; Olfr151; Olfr160; Semaphorin 3A