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.

Axonal Odorant Receptors Mediate Axon Targeting

“…See also Figure S8. location of olfactory glomeruli along the A-P axis, exhibits a global gradient along the A-P axis and a patchy distribution at the glomerular level (Assens et al, 2016;Col et al, 2007;Zapiec et al, 2016).…”

Coordination of olfactory receptor choice with guidance receptor expression and function in olfactory sensory neurons

“…In the fly, semaphorins organize the positioning of dendrites of projection neurons within the antennal lobe that serve as the targets for sensory axons, determine the ventromedial trajectory of OSN axons, and participate in glomerular targeting of sensory axons [ 10 , 15 , 57 – 59 ]. In the mouse, Sema3A helps to organize fasciculation of OSN axons in the olfactory nerve and contributes to the positioning of glomeruli in the bulb [ 60 – 63 ]. The clade and target specific requirement for nrp1a as compared to nrp1b observed for these two paralogs demonstrates that they have evolved to acquire independent functions in axon targeting in zebrafish.…”

The long tale of the calcium activated Cl−channels in olfactory transduction

“…87 the glomeruli. This model, though, has been questioned and requires further studies, [108][109][110] but the idea of having an OR-dependent regulation of the expression of guidance molecules involved in OB targeting and glomerular formation seems to hold because of the mosaic pattern of expression of such molecules in the OB (i.e., Nrp1). 94,108,110 Once the axons of OSNs expressing the same ORs converge in a general area, ligand-dependent activity determines the expression of molecules involved in axon sorting into individual glomeruli.…”