Cell surface carbohydrates and glomerular targeting of olfactory sensory neuron axons in the mouse

Abstract

Cell surface carbohydrates have been implicated in axon guidance and targeting throughout the nervous system. We have begun to test the hypothesis that, in the olfactory system, a differential distribution of cell surface carbohydrates may influence olfactory sensory neuron (OSN) axon targeting. Specifically, we have examined the spatial distribution of two different plant lectins, Ulex europaeus agglutinin (UEA) and Dolichos biflorus agglutinin (DBA), to determine whether they exhibit differential and reproducible projections onto the main olfactory bulb. Each lectin exhibited a unique spatial domain of glomerular labeling that was consistent across animals. UEA labeling was strongest in the ventral aspect of the olfactory bulb; DBA labeling was strongest in the dorsal aspect of the olfactory bulb. Some evidence for colocalization was present where these two borders intersected. Large areas of the glomerular layer were not labeled by either lectin. To determine whether patterns of lectin labeling were reproducible at the level of individual glomeruli, UEA labeling was assessed relative to M72-IRES-taulacZ- and P2-IRES-taulacZ-labeled axons. Although glomeruli neighboring these two identified glomeruli were consistently labeled with UEA, none of the lacZ positive axons was lectin labeled. Labeling of vomeronasal sensory neuron axons in the accessory olfactory bulb was more uniform for the two lectins. These data are the first to show a differential distribution of UEA vs. DBA labeling in the main olfactory bulb and are consistent with the hypothesis that a differential distribution of cell surface carbohydrates, a glycocode, may contribute to the targeting of OSN axons.

Localization of α1-2 Fucose Glycan in the Mouse Olfactory Pathway

“…We also showed that UEA-I-positive receptor cells possess scant OMP, a marker of mature olfactory receptor cells, suggesting that the positive cells at the basal region are immature receptor cells that extend axons to the MOB. Glycoconjugates including α1-2Fuc glycan were also located at the olfactory nerve layer and in several glomeruli of the MOB that are targets for axon endings of olfactory receptor cells, as reported by Lipscomb et al [2002Lipscomb et al [ , 2003, Salazar and Sánchez Quinteiro [2003] and Murrey et al [2009]. These findings suggest that α1-2Fuc glycan is associated with dendrite and neurite outgrowths within the primary pathway of the main olfactory system.…”

“…Although α1-2Fuc glycan has been histochemically localized in the mouse olfactory system using Ulex europaeus agglutinin-I (UEA-I) [Lundh et al, 1989;Ducray et al, 1999;Salazar et al, 2001;Lipscomb et al, 2002Lipscomb et al, , 2003Salazar and Sánchez Quinteiro, 2003;Murrey et al, 2009;Barrios et al, 2014;Kondoh et al, 2014], the findings are diverse. For example, we showed that α1-2Fuc glycan preferentially locates in the LOT and in the glomerular layer of the AOB of the ICR mouse [Kondoh et al, 2014] whereas other study groups have not found that UEA-I reacts with the mouse LOT.…”

β1,3-N-Acetylglucosaminyltransferase 1 Glycosylation Is Required for Axon Pathfinding by Olfactory Sensory Neurons

“…The stereotyped distribution of glycan-expressing glomeruli has led to the hypothesis that glycans may directly influence targeting of sensory axons (Lipscomb et al, 2003). One such glycan is terminal lactosamine, which is expressed by neurons that preferentially innervate ventromedial targets in embryonic rodents, consistent with a role in patterning olfactory connectivity (Schwarting and Crandall, 1991).…”

Patterning the developing and regenerating olfactory system

“…Individual OSN populations and glomeruli exhibit considerable heterogeneity in glycoconjugate expression by immunocytochemistry and lectin analysis, suggesting that glycans could influence targeting (Schwarting et al, 1992;Arnhold et al, 2001;Lipscomb et al, 2003). Although the complexity of cell surface carbohydrates has historically been a hindrance for understanding their functions, particularly in the brain, the current widespread availability of genetic models of glycan deficiency has recently led to a more comprehensive understanding of how defined glycan structures affect specific aspects of nervous system development.…”

“…Studies in species ranging from moths to mice have used plant lectins as a tool to map the trajectories of subsets of olfactory axons (Key and Akeson, 2003;Lipscomb et al, 2003;Gibson et al, 2004). Antibodies to various glycoforms of NCAM also define unique neuronal populations St John and Key, 2001) as have other monoclonal antibodies to glycan structures, such as HNK-1 and SSEA-1 that are also patterned elsewhere in the nervous system (Plank and Mai, 1992;Schwarting et al, 1987;Arnhold et al, 2001).…”