Morphological characteristics of the vomeronasal organ of the newborn Asian elephant (Elephas maximus).
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The 6-week-old Asian elephant (Elephas maximus) has a well-documented precocious flehmen response to pheromones, suggesting that the pheromone-detecting vomeronasal organ (VNO) is functional very early in the life of this species. To further document this, the VNOs of two newborn elephants were examined in situ and analyzed by light microscopy (LM) to ascertain their structural maturity at birth. A tubular, cartilage-encased VNO was located along the anterior base of each side of the nasal septum. Its rostral end was connected to a duct to the roof of the mouth; the caudal end was attached to a well-defined vomeronasal nerve projecting toward the brain. LM revealed distinctive differences in the mucosae bordering the horseshoe-shaped lumen: a concave, sensory mucosa, and a convex, nonsensory mucosa. Small groups of receptor neurons were observed among ciliated columnar cells in the sensory epithelium. Numerous unmyelinated nerve bundles and blood vessels filled the underlying lamina propria (LP) and a small section of the vomeronasal nerve was conspicuous at one edge. The nonsensory mucosa manifested a thinner epithelium that principally consisted of ciliated columnar cells, some of which showed a granular cytoplasm, and a conspicuous row of basal cells. The LP was replete with acinar glands and ducts that opened into the lumen. This study shows that the VNO of the newborn elephant has reached an advanced stage of structural maturity, closely resembling that of the adult. Its composition supports the view that flehmen at 6 weeks delivers pheromones to a functional VNO. (+info)
Stomatin-related olfactory protein, SRO, specifically expressed in the murine olfactory sensory neurons.
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We identified a stomatin-related olfactory protein (SRO) that is specifically expressed in olfactory sensory neurons (OSNs). The mouse sro gene encodes a polypeptide of 287 amino acids with a calculated molecular weight of 32 kDa. SRO shares 82% sequence similarity with the murine stomatin, 78% with Caenorhabditis elegans MEC-2, and 77% with C. elegans UNC-1. Unlike other stomatin-family genes, the sro transcript was present only in OSNs of the main olfactory epithelium. No sro expression was seen in vomeronasal neurons. SRO was abundant in most apical dendrites of OSNs, including olfactory cilia. Immunoprecipitation revealed that SRO associates with adenylyl cyclase type III and caveolin-1 in the low-density membrane fraction of olfactory cilia. Furthermore, anti-SRO antibodies stimulated cAMP production in fractionated cilia membrane. SRO may play a crucial role in modulating odorant signals in the lipid rafts of olfactory cilia. (+info)
Identification of V1R-like putative pheromone receptor sequences in non-human primates. Characterization of V1R pseudogenes in marmoset, a primate species that possesses an intact vomeronasal organ.
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The vomeronasal organ (VNO) is responsible in terrestrial vertebrates for the sensory perception of some pheromones, chemicals that elicit characteristic behaviors among individuals of the same species. Two multigene families (V1R, V2R) that encode proteins with seven putative transmembrane domains that are expressed selectively in different neuron subsets of the VNO have been described in rodents. Pheromone-induced behaviors and a functional VNO have been described in a number of mammals, but this sensory organ seems absent in adult catarrhines and apes, including humans. Until now, only pseudogenes have been isolated in humans, except one putative V1R (hV1RL1) sequence expressed in the main olfactory epithelium. We sought to isolate V1R-like genes in a New World monkey species, the marmoset Callithrix jacchus, that possesses an intact VNO and for which pheromone-induced behavior has been well documented. Using library screening approaches, we have identified five different sequences that exhibit characteristic features of V1R sequences, but that are non-functional pseudogenes. In an attempt to sort out functional V1R genes, we next cloned by polymerase chain reaction (PCR) the primate orthologues of hV1RL1. This approach was successful for gorilla, chimpanzee and orangutan, but not for the other species, including marmoset, probably because these species are too divergent from humans. Chimpanzee and orangutan V1RL1 genes are pseudogenes, whereas the gorilla counterpart is potentially functional. These observations raise the possibility that the V1R family has evolved in such a manner in mammals that every species that relies on a VNO-mediated sensory function possesses its own set of functional vomeronasal genes. (+info)
Molecular mechanisms for migration of placodally derived GnRH neurons.
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Gonadotropin-releasing hormone (GnRH) neurons, critical for reproduction, are derived from the nasal placode and migrate into the brain along nasal axons. GnRH neurons appear to diverge from olfactory sensory cells during early stages of nasal placode differentiation. However, GnRH neurons rely on olfactory/vomeronasal axons as their pathway to the central nervous system (CNS). A novel factor, termed nasal embryonic luteinizing hormone-releasing hormone factor (NELF), was discovered in a differential screen of migrating versus nonmigrating GnRH neurons. NELF is expressed in olfactory sensory cells and GnRH cells in nasal areas. Antisense experiments demonstrated that knock-down of NELF decreased olfactory axon outgrowth and GnRH neuronal migration. These results indicate that NELF plays a role as a guidance molecule for olfactory axon projections and migration of GnRH cells. We hypothesize that NELF acts via a homophilic interaction and that NELF expression is critical for reproduction by insuring that GnRH cells reach the CNS. Furthermore, down-regulation of NELF on GnRH cells as they enter the telencephalon may allow GnRH cells to distinguish a different pathway(s) in the CNS (from those leading to olfactory regions) and thereby facilitate establishment of the appropriate adult-like GnRH distribution. (+info)
Pheromone binding by polymorphic mouse major urinary proteins.
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Mouse major urinary proteins (MUPs) have been proposed to play a role in regulating the release and capture of pheromones. Here, we report affinity measurements of five recombinant urinary MUP isoforms (MUPs-I, II, VII, VIII, and IX) and one recombinant nasal isoform (MUP-IV) for each of three pheromonal ligands, (+/-)-2-sec-butyl-4,5-dihydrothiazole (SBT), 6-hydroxy-6-methyl-3-heptanone (HMH), and (+/-)dehydro-exo-brevicomin (DHB). Dissociation constants for all MUP-pheromone pairs were determined by isothermal titration calorimetry, and data for SBT were corroborated by measurements of intrinsic protein fluorescence. We also report the isolation of MUP-IV protein from mouse nasal extracts, in which MUP-IV mRNA has been observed previously. The affinity of each MUP isoform for SBT (K(d) approximately 0.04 to 0.9 micro M) is higher than that for DHB (K(d) approximately 26 to 58 micro M), which in turn is higher than that for HMH (K(d) approximately 50 to 200 micro M). Isoforms I, II, VIII, and IX show very similar affinities for each of the ligands. MUP-VII has approximately twofold higher affinity for SBT but approximately twofold lower affinity for the other pheromones, whereas MUP-IV has approximately 23-fold higher affinity for SBT and approximately fourfold lower affinity for the other pheromones. The variations in ligand affinities of the MUP isoforms are consistent with structural differences in the binding cavities of the isoforms. The data indicate that the concentrations of available pheromones in urine may be influenced by changes in the expression levels of urinary MUPs or the excretion levels of other MUP ligands. The variation in pheromone affinities of the urinary MUP isoforms provides only limited support for the proposal that MUP heterogeneity plays a role in regulating profiles of available pheromones. However, the binding data support the proposed role of nasal MUPs in sequestering pheromones and possibly transporting them to their receptors. (+info)
The vomeronasal organ and chemical sensitivity: a hypothesis.
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Environmental exposures to very low levels of airborne chemicals are associated with adverse symptoms, often affecting multiple organ systems, in the phenomenon of chemical sensitivity (CS). Recent surveys suggest a significant prevalence of chemically sensitive subjects in the United States, but the mechanism linking exposure to symptoms remains unclear, despite the advancement of a variety of theoretical models. In many of these models, exposure of the nasal respiratory system to an airborne agent is the first step in the pathway leading to symptoms. In this article, we advance the hypothesis that interactions between environmental chemicals and the vomeronasal organ (VNO) may play a role in the etiology of CS. The VNO, a bilateral, tubular organ located in the nose, serves in animals as part of a sensitive chemosensory system; however, evidence suggesting that the VNO retains a functional role in the adult human is controversial. Reported characteristics of the human VNO relevant to CS, including location, prevalence, selective sensitivity to airborne chemical exposure, and capacity to produce systemic effects, are discussed within the context of this ongoing debate. Beyond relevance to CS, the demonstration of an active, adult VNO could have significant impact on environmental toxicology. (+info)
Characterization of cAMP degradation by phosphodiesterases in the accessory olfactory system.
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To characterize the potential role of cAMP in pheromone transduction, we have examined the occurrence of cyclic nucleotide phosphodiesterases (PDEs) in the mouse vomeronasal organ (VNO). We show that the cAMP-specific isoforms PDE4A and PDE4D are found preferentially in the apical and basal layers, respectively, of the VNO neuroepithelium and in the rostral (PDE4A) and caudal (PDE4D) portions of the accessory olfactory bulb glomerular layer. Assays for cAMP hydrolysis showed that PDE activity in VNO homogenates was about half that measured in the cerebral cortex and olfactory epithelium, and the proportion of total activity inhibited by rolipram, a PDE4-specific inhibitor, was approximately 40%. Activity in the VNO was enhanced 60% by Ca(2+) and calmodulin (CaM), implicating the presence of Ca(2+)/CaM-dependent PDE1. Zaprinast, which is known to inhibit PDE1C isoforms, completely suppressed Ca(2+)/CaM-stimulated activity and, together, zaprinast and rolipram inhibited cAMP hydrolysis by approximately 70%. Our results suggest that PDE1 and PDE4 isoforms are the primary source of cAMP degradation in the VNO. (+info)
Arachidonic acid plays a role in rat vomeronasal signal transduction.
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Sensory neurons of the vomeronasal organ (VNO) detect volatile chemicals that are released by conspecific animals and convey information about social and reproductive behavior. The signal transduction pathway in vomeronasal receptor neurons (VRNs) is not known in detail, but is believed to be distinct from that of the sensory neurons of the main olfactory system. Many of the identified olfactory transduction components are not expressed by VRNs. Using Ca2+ imaging and electrophysiological recordings, we investigated the signal transduction pathway of urine perception and the possible role of polyunsaturated fatty acids (PUFAs) as intracellular messengers in freshly dissociated rat VNO neurons. We found that application of urine induced a transient increase in intracellular Ca2+ that was dependent on the activity of phospholipase C and diacylglycerol (DAG) lipase. The Ca2+ transient was not dependent on depletion of intracellular Ca2+ stores but was dependent on the presence of extracellular Ca2+. Furthermore, the urine response was not sensitive to modulators of adenylate cyclase and inhibitors of inositol 1,4,5-trisphosphate receptors. Application of PUFAs (linolenic acid and arachidonic acid, synthesized in living cells from DAG) also elicited Ca2+ transients in fura 2 measurements and inward currents in whole-cell voltage-clamp recordings. Pharmacological inhibition of lipoxygenase and cyclooxygenase induced a transient increase in intracellular Ca2+, possibly by increasing the endogenous level of PUFAs, leading to activation of transduction channels. These data provide evidence for a role of PUFAs in rat vomeronasal signal transduction. (+info)