Patterned Arrangements of Olfactory Receptor Gene Expression in Zebrafish are Established by Radial Movement of Specified Olfactory Sensory Neurons

Abstract

Spatial restriction of olfactory receptor (OR) gene expression in peripheral sense organs is a common phenomenon across species, suggesting that zonal OR expression somehow contributes to olfactory function. In zebrafish OR expression patterns reminiscent of zones occur as concentric domains with preferred diameters for different ORs. However, the function and the developmental origin of the pattern are unknown. Here we investigate olfactory sensory neuron (OSN) neurogenesis in the adult zebrafish olfactory epithelium (OE) to understand how the zonally organized OR pattern is established and maintained during the lifetime of the animal. We find that OSNs are generated from two discontinuous proliferation zones located at the central and peripheral edge of the sensory OE. OSNs turn on OR expression soon after they exit mitosis and invade the sensory tissue, approaching each other from both ends of the OE. Biased generation of OSN subpopulations at both neurogenic sites and elimination of OSNs along their route across the OE generates the impression of OR-specific expression domains. We formulated a simple mathematical model based on exact parameters derived from our analysis of OSN neurogenesis, which accurately generates OR-like distributions without the need to invoke molecular signals to pattern the OE.

Overlapping but distinct topology for zebrafish V2R-like olfactory receptors reminiscent of odorant receptor spatial expression zones

“…Lastly, any potential mechanism has to take into account the constant renewal of olfactory sensory neurons during adult life. The average lifetime of zebrafish OSN has been estimated as around one month [ 29 ], so at the age examined, several rounds of neurogenesis have already occurred blurring any potential relation to organismal age.…”

“…It is noteworthy that the zebrafish olfactory organ possesses two proliferative zones, one at the apex of the lamella, the other at the outer border of the sensory region [ 30 ] . A recent publication [ 29 ] examining three zebrafish odorant receptor genes has suggested that different olfactory progenitor cells might migrate differentially from these proliferative zones, which could result in a pattern of broad expression zones with different centers-of-gravity . While beyond the scope of the current investigation, it will be interesting to see whether OlfC genes follow a similar pattern.…”

The Olfactory System of Zebrafish as a Model for the Study of Neurotoxicity and Injury: Implications for Neuroplasticity and Disease

“…In addition to having a well-characterized morphology and neuronal circuitry, the olfactory system of zebrafish presents remarkable regeneration, repair, and reorganization mechanisms in basal states in response to injury. Both the olfactory organ and the olfactory bulb present continuous neurogenesis and neuronal turnover throughout the organism’s lifespan [24,38,39,40,41,42]. These features make the olfactory system of zebrafish an ideal model to study mechanisms of olfaction processing, olfactory dysfunction, and regeneration following damage.…”

“…OSNs express a combination of discrete olfactory receptors (ORs), and groups of OSNs expressing the same olfactory receptors are positioned in defined zones within the rosette [38,51,52]. Evidence suggests that zebrafish OSNs follow the “one neuron–one receptor” configuration that has been described in mammals, although a couple of exceptions in ciliated OSNs have been reported [44,53,54].…”

“…ORs belong to the G protein-coupled receptor (GPCR) superfamily and are further divided in three types: (1) olfactory receptors (ORs), the most abundant type, further divide into families and subfamilies [27,38,44,59,60]; (2) trace amine-associated receptors (TAARs) detect volatile amines [61,62,63,64,65,66]; and (3) vomeronasal receptors (V1Rs, V2Rs) are described as putative pheromone receptors [65,67,68,69,70]. Ciliated OSNs, which preferentially respond to bile acids, express OR-type and TAAR-type receptors coupled to Gαolf [56,61,71].…”