scholarly journals Olfactory Receptor Gene Regulation in Insects: Multiple Mechanisms for Singular Expression

2021 ◽  
Vol 15 ◽  
Author(s):  
Kaan Mika ◽  
Richard Benton
Keyword(s):  
Olfactory Receptor ◽  
Internal State ◽  
Receptor Gene ◽  
Expression Patterns ◽  
Olfactory Receptors ◽  
Regulatory Elements ◽  
Receptor Expression ◽  
Outstanding Question ◽  
The Brain ◽  
Large Repertoire

The singular expression of insect olfactory receptors in specific populations of olfactory sensory neurons is fundamental to the encoding of odors in patterns of neuronal activity in the brain. How a receptor gene is selected, from among a large repertoire in the genome, to be expressed in a particular neuron is an outstanding question. Focusing on Drosophila melanogaster, where most investigations have been performed, but incorporating recent insights from other insect species, we review the multilevel regulatory mechanisms of olfactory receptor expression. We discuss how cis-regulatory elements, trans-acting factors, chromatin modifications, and feedback pathways collaborate to activate and maintain expression of the chosen receptor (and to suppress others), highlighting similarities and differences with the mechanisms underlying singular receptor expression in mammals. We also consider the plasticity of receptor regulation in response to environmental cues and internal state during the lifetime of an individual, as well as the evolution of novel expression patterns over longer timescales. Finally, we describe the mechanisms and potential significance of examples of receptor co-expression.

scholarly journals Coordinating Receptor Expression and Wiring Specificity in Olfactory Receptor Neurons

2019 ◽  
Author(s):  
Hongjie Li ◽  
Tongchao Li ◽  
Felix Horns ◽  
Jiefu Li ◽  
Qijing Xie ◽  
...  
Keyword(s):  
Olfactory Receptor ◽  
Olfactory Receptors ◽  
Receptor Expression ◽  
Olfactory Receptor Neurons ◽  
Unique Combination ◽  
Axon Targeting ◽  
Transcriptional Regulatory ◽  
Receptor Neurons ◽  
Transcriptional Regulatory Mechanisms ◽  
The Brain

The ultimate function of a neuron is determined by both its physiology and connectivity, but the transcriptional regulatory mechanisms that coordinate these two features are not well understood1–4. The Drosophila Olfactory receptor neurons (ORNs) provide an excellent system to investigate this question. As in mammals5, each Drosophila ORN class is defined by the expression of a single olfactory receptor or a unique combination thereof, which determines their odor responses, and by the single glomerulus to which their axons target, which determines how sensory signals are represented in the brain6–10. In mammals, the coordination of olfactory receptor expression and wiring specificity is accomplished in part by olfactory receptors themselves regulating ORN wiring specificity11–13. However, Drosophila olfactory receptors do not instruct axon targeting6, 14, raising the question as to how receptor expression and wiring specificity are coordinated. Using single-cell RNA-sequencing and genetic analysis, we identified 33 transcriptomic clusters for fly ORNs. We unambiguously mapped 17 to glomerular classes, demonstrating that transcriptomic clusters correspond well with anatomically and physiologically defined ORN classes. We found that each ORN expresses ~150 transcription factors (TFs), and identified a master TF that regulates both olfactory receptor expression and wiring specificity. A second TF plays distinct roles, regulating only receptor expression in one class and only wiring in another. Thus, fly ORNs utilize diverse transcriptional strategies to coordinate physiology and connectivity.

Spatially Organized Response Zones in Rat Olfactory Epithelium

1997 ◽  
Vol 77 (4) ◽  
pp. 1950-1962 ◽  
Author(s):  
John W. Scott ◽  
Donna E. Shannon ◽  
Jeff Charpentier ◽  
Lisa M. Davis ◽  
Craig Kaplan
Keyword(s):  
Gene Expression ◽  
Functional Groups ◽  
Olfactory Epithelium ◽  
Olfactory Receptor ◽  
Receptor Gene ◽  
Chemical Properties ◽  
Receptor Expression ◽  
Response Distribution ◽  
Chemical Structures ◽  
Four Electrodes

Scott, John W., Donna E. Shannon, Jeff Charpentier, Lisa M. Davis, and Craig Kaplan. Spatially organized response zones in rat olfactory epithelium. J. Neurophysiol. 77: 1950–1962, 1997. Electroolfactogram recordings were made with a four-electrode assembly from the olfactory epithelium overlying the endoturbinate bones facing the nasal septum. In this study we tested whether odors of different chemical structures produce maximal responses along longitudinally oriented regions following the olfactory receptor gene expression zones described in the literature. The distribution of responses along the dorsal-to-ventral direction of this epithelium (i.e., across the expression zones) was tested in two types of experiments. In one, four electrodes were fixed along the dorsal-to-ventral axis of one turbinate bone. In the other, four electrodes were placed in corresponding positions on four turbinate bones and moved together up toward the top of the bone. These experiments compared the odorants limonene and α-terpinene, which are simple hydrocarbons, with carvone and menthone, which differ from the hydrocarbons by the presence of ketone groups. All responses were standardized to an amyl acetate or ethyl butyrate standard. The responses to limonene and α-terpinene were often larger for the ventral electrodes. The responses to carvone and menthone were largest for the dorsal electrodes. Intermediate electrodes gave responses that were intermediate in amplitude for these odors. The possibility that direction of air flow caused the observed response distributions was directly tested in experiments with odor nozzles placed in two positions. The relatively larger dorsal responses to carvone and relatively larger ventral responses to limonene were present despite odor nozzle position. We conclude that the responses to this set of odors vary systematically in a fashion parallel to the four gene expression zones. The odorant property that governs this response distribution may be related to the presence of oxygen-containing functional groups. Certain odors evoked larger responses at the intermediate electrode sites than at other sites. Cineole was the best example of this effect. This observation shows that not all oxygen-containing functional groups produce the same effect. Although we cannot exclude other possible mechanisms, these three response gradients may be produced by the four receptor expression zones described for many of the putative olfactory receptor genes. Therefore many of the receptors in each zone may share common properties. It remains to be determined whether this zonal input is significant in central odor processing. However, the correlation of odor chemical properties with the structure of receptor molecules in each zone may provide significant leads to structure-function relationships in vertebrate olfaction.

scholarly journals Olfactory receptors are displayed on dog mature sperm cells.

1993 ◽  
Vol 123 (6) ◽  
pp. 1441-1452 ◽  
Author(s):  
P Vanderhaeghen ◽  
S Schurmans ◽  
G Vassart ◽  
M Parmentier
Keyword(s):  
Olfactory Receptor ◽  
Germ Line ◽  
Receptor Gene ◽  
Olfactory Receptors ◽  
Olfactory Mucosa ◽  
Mature Sperm ◽  
Sperm Cells ◽  
Olfactory Receptor Gene ◽  
Mammalian Sperm ◽  
Expression Site

Olfactory receptors constitute a huge family of structurally related G protein-coupled receptors, with up to a thousand members expected. We have shown previously that genes belonging to this family were expressed in the male germ line from both dog and human. The functional significance of this unexpected site of expression was further investigated in the present study. We demonstrate that a few dog genes representative of various subfamilies of olfactory receptors are expressed essentially in testis, with little or no expression in olfactory mucosa. Other randomly selected members of the family show the expected site of expression, restricted to the olfactory system. Antibodies were generated against the deduced amino acid sequence of the most abundantly expressed olfactory receptor gene in dog testis. The purified serum was able to detect the gene product (DTMT receptor) in late round and elongated spermatids, as well as in the cytoplasmic droplet that characterizes the maturation of dog sperm cells, and on the tail midpiece of mature spermatozoa. Western blotting further confirmed the presence of a 40-kD immunoreactive protein in the membrane of mature sperm cells. Altogether , these results demonstrate that the main expression site of a subset of the large olfactory receptor gene family is not olfactory mucosa but testis. This expression correlates with the presence of the corresponding protein during sperm cell maturation, and on mature sperm cells. The pattern of expression is consistent with a role as sensor for unidentified chemicals possibly involved in the control of mammalian sperm maturation, migration, and/or fertilization.

scholarly journals Molecular regulation of the oxytocin receptor in peripheral organs

2003 ◽  
Vol 30 (2) ◽  
pp. 109-115 ◽  
Author(s):  
T Kimura ◽  
F Saji ◽  
K Nishimori ◽  
K Ogita ◽  
H Nakamura ◽  
...  
Keyword(s):  
Receptor Gene ◽  
Physiological Role ◽  
Single Copy ◽  
Regulatory Elements ◽  
Oxytocin Receptor ◽  
Specific Pattern ◽  
Receptor Expression ◽  
Oxytocin Receptor Gene ◽  
Tissue Specific ◽  
Fusion Construct

The oxytocin receptor belongs to the G-protein-coupled seven transmembrane receptor superfamily. Its main physiological role is regulating the contraction of uterine smooth muscle at parturition and the ejection of milk from the lactating breast. Oxytocin receptor expression is observed not only in the myometrium and mammary gland but also in the endometrium, decidua, ovary, testis, epididymis, vas deferens, thymus, heart and kidney, as well as in the brain. The expression profile shows a tissue-specific as well as a stage-specific pattern. The oxytocin receptor gene is a single-copy gene consisting of four exons and three introns, localized at 3p25-3p26.2 in the human chromosome. In transfection studies using a fusion construct containing the promoter region of the oxytocin receptor gene inserted in a reporter plasmid, neither proinflammatory cytokines nor oestrogen directly activate the gene. The nuclear fractions from up-regulated (term myometrium) and down-regulated (non-pregnant myometrium) tIssues show differential patterns of protein binding to the 5'-flanking region, and a human homologue of chicken MafF has been cloned as a term-myometrium-specific oxytocin receptor modulator. The oxytocin receptor gene appears to be highly methylated. Methylation around intron 1 and in intron 3 might contribute to tIssue-specific suppression of the gene. The oxytocin receptor is also regulated by desensitization, whose mechanism appears to involve loss of ligand-binding activity of the protein as well as suppression of the oxytocin receptor mRNA transcription. These findings taken together indicate that the oxytocin receptor is regulated in a very complicated manner, and the transcriptional regulatory elements critical for this regulation should be investigated further.

scholarly journals Non-canonical odor coding ensures unbreakable mosquito attraction to humans

2020 ◽  
Author(s):  
Meg A. Younger ◽  
Margaret Herre ◽  
Alison R. Ehrlich ◽  
Zhongyan Gong ◽  
Zachary N. Gilbert ◽  
...  
Keyword(s):  
Olfactory System ◽  
Receptor Gene ◽  
Gene Families ◽  
Receptor Expression ◽  
Olfactory Neurons ◽  
Odor Cues ◽  
Chemosensory Receptor ◽  
Single Receptor ◽  
The Brain

SUMMARYFemale Aedes aegypti mosquitoes show strong innate attraction to humans. This chemosensory behavior is critical to species survival because females require a blood-meal to reproduce. Humans, the preferred host of Ae. aegypti, produce a complex blend of odor cues along with carbon dioxide (CO2) that attracts females ready to bite. Mosquitoes detect these cues with heteromeric ligand-gated ion channels encoded by three different chemosensory receptor gene families. A common theme in other species is that olfactory neurons express a single receptor that defines their chemical specificity and that they extend axons that converge upon dedicated glomeruli in the first sensory processing center in the brain. Such an organization permits the brain to segregate olfactory information and monitor activity of individual glomeruli to interpret what smell has been encountered. We have discovered that Ae. aegypti uses an entirely different organizational principle for its olfactory system. Using genetic strains that label subpopulations of olfactory neurons, we found that many neurons co-express multiple members of at least two of the chemosensory receptor families. This unexpected co-expression is functional, as assessed by in vivo calcium imaging showing that a given glomerulus is activated by multiple ligands detected by different receptor families. This has direct functional consequences for mosquito behavior. Mutant mosquitoes that cannot sense CO2 can be behaviorally activated by a volatile amine that stimulates the CO2 glomerulus. This non-canonical olfactory system organization featuring overlapping receptor expression may explain the female mosquito’s robust and “unbreakable’ attraction to humans.

scholarly journals Decoding the olfactory map: targeted transcriptomics link olfactory receptors to glomeruli

2021 ◽  
Author(s):  
Kevin Zhu ◽  
Shawn Burton ◽  
Maira Nagai ◽  
Justin Silverman ◽  
Claire De March ◽  
...  
Keyword(s):  
Olfactory Bulb ◽  
High Throughput ◽  
Olfactory Receptor ◽  
Specific Activity ◽  
Olfactory Receptors ◽  
Receptor Expression ◽  
Central Neurons ◽  
Target Capture ◽  
Olfactory Systems ◽  
Peripheral Sensory

Abstract Sensory processing in olfactory systems is organized across olfactory bulb glomeruli, wherein axons of peripheral sensory neurons expressing the same olfactory receptor co-terminate to transmit receptor-specific activity to central neurons. Understanding how receptors map to glomeruli is therefore critical to understanding olfaction. High-throughput spatial transcriptomics is a rapidly advancing field, but low-abundance olfactory receptor expression within glomeruli has previously precluded high-throughput mapping of receptors to glomeruli. Here we combined sequential sectioning along the anteroposterior, dorsoventral, and mediolateral axes with target capture enrichment sequencing to overcome low-abundance target expression. This strategy allowed us to spatially map 86% of olfactory receptors across the olfactory bulb and uncover a relationship between OR sequence and glomerular position.

Ectopic olfactory receptors in the respiratory system

2020 ◽  
Vol 29 (6) ◽  
pp. 734-738
Author(s):  
V. N. Mineev
Keyword(s):  
Smooth Muscle ◽  
Olfactory Receptor ◽  
Olfactory Receptors ◽  
Receptor Activation ◽  
Neuroendocrine Cells ◽  
Receptor Expression ◽  
Special Role ◽  
Concentration Data ◽  
Cell Functions

New findings and concepts on a role of so-called “ectopic” chemosensory receptors arise recently. The ectopic receptors are expressed outside their classical localization (nasal cavity) and referred to as extra-nasal olfactory receptors. Functional investigations of the ectopic olfactory receptors in the lungs are also ongoing. To date, it is well-known that molecules of odorous substances (odorants) bind to the G-protein-associated olfactory receptor (Gαolf) that can activate type III adenylate cyclase and increase concentration of a secondary messenger, cyclic adenosine monophosphate (cAMP). In turn, this induces the opening of cAMP-dependent cationic channels including calcium channels. Olfactory receptor activation in neuroendocrine cells of the lungs affected serotonin release which decreased after the stimulation of those cells by an odorant. Amyl butyrate and burgenal, agonists of OR2AG1 and OR1D2 olfactory receptors, respectively, affect smooth muscle contractibility in human bronchi. Amyl butyrate inhibits histamine-induces muscle contractibility, whereas burgenal increases the smooth muscle contractibility. Both the processes are mediated by cAMP-dependent increase in the intracellular calcium concentration. Data have been published about the receptor expression on immune cells such as monocytes, natural killers, T- and B-lymphocites, and polymorphonuclears. Ectopic olfactory receptors are thought to participate in modulation (controlling) of intrinsic cell functions which provide a special role of inflammatory cells in asthma. In future, the olfactory receptor modulation could be probably used as a novel therapeutic approach in asthma and other chronic inflammatory lung diseases.

scholarly journals Developmental expression of retinoic acid receptors (RARs)

2009 ◽  
Vol 7 (1) ◽  
pp. nrs.07006 ◽  
Author(s):  
Pascal Dollé
Keyword(s):  
Retinoic Acid ◽  
Receptor Gene ◽  
Expression Patterns ◽  
Dominant Negative ◽  
Receptor Expression ◽  
Retinoic Acid Receptors ◽  
Developmental Expression ◽  
Specific Expression ◽  
Functional Studies ◽  
Organ Systems

Here, I review the developmental expression features of genes encoding the retinoic acid receptors (RARs) and the ‘retinoid X’ or rexinoid receptors (RXRs). The first detailed expression studies were performed in the mouse over two decades ago, following the cloning of the murine Rar genes. These studies revealed complex expression features at all stages of post-implantation development, one receptor gene (Rara) showing widespread expression, the two others (Rarb and Rarg) with highly regionalized and/or cell type-specific expression in both neural and non-neural tissues. Rxr genes also have either widespread (Rxra, Rxrb), or highly-restricted (Rxrg) expression patterns. Studies performed in zebrafish and Xenopus demonstrated expression of Rar and Rxr genes (both maternal and zygotic), at early pre-gastrulation stages. The eventual characterization of specific enzymes involved in the synthesis of retinoic acid (retinol/retinaldehyde dehydrogenases), or the triggering of its catabolism (CYP26 cytochrome P450s), all of them showing differential expression patterns, led to a clearer understanding of the phenomenons regulated by retinoic acid signaling during development. Functional studies involving targeted gene disruptions in the mouse, and additional approaches such as dominant negative receptor expression in other models, have pinpointed the specific, versus partly redundant, roles of the RARs and RXRs in many developing organ systems. These pleiotropic roles are summarized hereafter in relationship to the receptors’ expression patterns.

scholarly journals Revisiting olfactory receptors as putative drivers of cancer

2017 ◽  
Vol 2 ◽  
pp. 9 ◽  
Author(s):  
Marco Ranzani ◽  
Vivek Iyer ◽  
Ximena Ibarra-Soria ◽  
Martin Del Castillo Velasco-Herrera ◽  
Mathew Garnett ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Cell Lines ◽  
Cancer Cell ◽  
Olfactory Receptor ◽  
Receptor Gene ◽  
Signal Transduction Pathway ◽  
Olfactory Receptors ◽  
Cancer Cell Lines ◽  
Specific Manner ◽  
Olfactory Receptor Genes

Background: Olfactory receptors (ORs) recognize odorant molecules and activate a signal transduction pathway that ultimately leads to the perception of smell. This process also modulates the apoptotic cycle of olfactory sensory neurons in an olfactory receptor-specific manner. Recent reports indicate that some olfactory receptors are expressed in tissues other than the olfactory epithelium suggesting that they may have pleiotropic roles. Methods: We investigated the expression of 301 olfactory receptor genes in a comprehensive panel of 968 cancer cell lines. Results: Forty-nine per cent of cell lines show expression of at least one olfactory receptor gene. Some receptors display a broad pattern of expression across tumour types, while others were expressed in cell lines from a particular tissue. Additionally, most of the cancer cell lines expressing olfactory receptors express the effectors necessary for OR-mediated signal transduction. Remarkably, among cancer cell lines, OR2C3 is exclusively expressed in melanoma lines. We also confirmed the expression of OR2C3 in human melanomas, but not in normal melanocytes. Conclusions: The pattern of OR2C3 expression is suggestive of a functional role in the development and/or progression of melanoma. Some olfactory receptors may contribute to tumorigenesis.

scholarly journals Human Somatostatin SST4 Receptor Transgenic Mice: Construction and Brain Expression Pattern Characterization

2021 ◽  
Vol 22 (7) ◽  
pp. 3758
Author(s):  
Balázs Nemes ◽  
Kata Bölcskei ◽  
Angéla Kecskés ◽  
Viktória Kormos ◽  
Balázs Gaszner ◽  
...  
Keyword(s):  
In Vivo Imaging ◽  
Regulatory Elements ◽  
Receptor Expression ◽  
Luciferase Reporter ◽  
Mouse Line ◽  
Humanized Mouse ◽  
Peripheral Tissues ◽  
And Function ◽  
The Brain

Somatostatin receptor subtype 4 (SST4) has been shown to mediate analgesic, antidepressant and anti-inflammatory functions without endocrine actions; therefore, it is proposed to be a novel target for drug development. To overcome the species differences of SST4 receptor expression and function between humans and mice, we generated an SST4 humanized mouse line to serve as a translational animal model for preclinical research. A transposon vector containing the hSSTR4 and reporter gene construct driven by the hSSTR4 regulatory elements were created. The vector was randomly inserted in Sstr4-deficient mice. hSSTR4 expression was detected by bioluminescent in vivo imaging of the luciferase reporter predominantly in the brain. RT-qPCR confirmed the expression of the human gene in the brain and various peripheral tissues consistent with the in vivo imaging. RNAscope in situ hybridization revealed the presence of hSSTR4 transcripts in glutamatergic excitatory neurons in the CA1 and CA2 regions of the hippocampus; in the GABAergic interneurons in the granular layer of the olfactory bulb and in both types of neurons in the primary somatosensory cortex, piriform cortex, prelimbic cortex and amygdala. This novel SST4 humanized mouse line might enable us to investigate the differences of human and mouse SST4 receptor expression and function and assess the effects of SST4 receptor agonist drug candidates.

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