Olfactory receptor neuronal dendrites become mostly intra‐sustentacularly enwrapped upon maturity

Abstract

The mammalian olfactory epithelium (OE) sustains persistent neurogenesis even in the adult. Sustentacular cells therein play both epithelial and neuroglial roles, although their relation with olfactory receptor neurons (ORNs) and their function in ORN maturation remain insufficiently understood. Sustentacular wrapping of ORN dendrites has been long known but always considered a minor presence, as opposed to the supposedly unwrapped majority of ORN dendrites at inter-sustentacular borderlines. Using immunofluorescence, confocal and immuno-electron microscopy, the current study examined cytoarchitectonic organization and maturation of ORN dendrites at the rat OE apical layer. Contrary to common belief, the observations here on tangential histological sections of the OE apical junctional belt layer showed on average 53.93% sustentacular cell-enwrapped, 18.46% partially wrapped (in the vertical grooves on the sides of sustentacular apices) and 27.61% unwrapped ORN dendrites (at the borderlines between sustentacular cells). The enwrapped dendrites were found within the confines of sustentacular apices but linked to the sides of the latter each by a mesentery (mesodendrite) of sustentacular plasma membranes and autotypic cell junctions. Up to six dendrites were seen in one sustentacular apical process. As marked by high and low immunoreactivity for class III beta-tubulin, respectively, immature and mature ORN dendrites accounted on average for 12.46 and 87.54% of the total ORN dendrites at the OE apical layer. By correlative analysis of the maturity level and wrapping status, most immature ORN dendrites were found unwrapped (immature unwrapped = 9.71% of the total dendrites), and practically no immature dendrites appeared enwrapped. In contrast, mature ORN dendrites comprised all the enwrapped (mature enwrapped = 53.93% of the total), most of the partially wrapped (mature partially wrapped = 15.71% of the total) and a portion of the unwrapped ORN dendrites (mature unwrapped = 17.9% of the total dendrites). Based on the current findings and previous data by other researchers, it is concluded that immature ORN dendrites emerge vertically from the OE apical surface between sustentacular cell apices. A large majority of the newly emerged dendrites then undergo sideways migration, sustentacular enwrapment and further maturation. Only a small minority of the newly emerged dendrites reach maturity and remain unwrapped. These divergent maturational courses imply structural or functional differences between the enwrapped and unwrapped mature ORN dendrites.

Tailoring Formulations for Intranasal Nose-to-Brain Delivery: A Review on Architecture, Physico-Chemical Characteristics and Mucociliary Clearance of the Nasal Olfactory Mucosa

“…Their particular role and function still needs to be elucidated. While OEC wrap around OSN axons, SUS are enclosed around OSN dendrites, to ensure structural stability and to maintain ionic integrity [ 41 , 42 ]. Enwrapping occurs with OSN maturation: while most of the immature OSN dendrites are unwrapped, the majority of mature OSN dendrites are enwrapped with SUS [ 41 ].…”

“…While OEC wrap around OSN axons, SUS are enclosed around OSN dendrites, to ensure structural stability and to maintain ionic integrity [ 41 , 42 ]. Enwrapping occurs with OSN maturation: while most of the immature OSN dendrites are unwrapped, the majority of mature OSN dendrites are enwrapped with SUS [ 41 ]. Juxtanodin, an actin cytoskeleton-related protein, is present in SUS that plays also an important role in forming the myelin sheaths of oligodendroglia in the CNS.…”

“…It is thought that juxtanodin regulates the interaction of SUS cells with OSN in the same way as it is described for oligodendroglia. Cell membranes of SUS enwrapping adjacent OSN contain gap junctions [ 41 , 43 ]. SUS do not only enwrap mature OSN dendrites, they also provide an environment for regeneration.…”

SARS-CoV-2 receptor and entry genes are expressed by sustentacular cells in the human olfactory neuroepithelium

“…For Figure 1, olfactory cascade genes were selected for their known expression specificity in the olfactory neurosensory epithelium, and 3 OR genes were arbitrarily selected amongst the top 25 most expressed OR genes. ERMN was selected as a marker of sustentacular cells 13,31 .…”

“…Each sensory neuron extends a dendrite that ends in multiple and long specialized ciliae, which are covered with odorant receptors and bath in the mucus that lines the nasal cavity. Olfactory sensory neuron dendrites are enwrapped inside specialized cells, the sustentacular cells 13 , whose nuclei and cell bodies line the external layer of the thick neuroepithelium (although they remain attached to the basal lamina). The role played by the latter in maintaining the integrity and function of the neuroepithelium is critical, in a very similar way that Sertoli cells support germ cell development and survival.…”