Chem. Senses 26: 207-213,
2001
© Oxford University Press 2001
SYMPOSIUM: AChemS XXII Symposium |
The Molecular Logic of Olfaction in Drosophila
Center for Neurobiology and Behavior, Columbia University, 701 West 168th Street, New York, NY 10032, USA
Correspondence to be sent to current address: Leslie B. Vosshall, Laboratory of Neurogenetics and Behavior, Rockefeller University, 1230 York Avenue, Box 63, New York, NY 10021, USA. e-mail: leslie{at}mail.rockefeller.edu
Abstract
Drosophila fruit flies display robust olfactory-driven behaviors with an olfactory system far simpler than that of vertebrates. Endowed with 
1300 olfactory receptor neurons, these insects are able to recognize and discriminate between a large number of distinct odorants. Candidate odorant receptor molecules were identified by complimentary approaches of differential cloning and genome analysis. The Drosophila odorant receptor (DOR) genes encode a novel family of proteins with seven predicted membrane-spanning domains, unrelated to vertebrate or nematode chemosensory receptors. There are on the order of 60 or more members of this gene family in the Drosophila genome, far fewer than the hundreds to thousands of receptors found in vertebrates or nematodes. DOR genes are selectively expressed in small subsets of olfactory neurons, in expression domains that are spatially conserved between individuals, bilaterally symmetric and not sexually dimorphic. Double in situ RNA hybridization with a number of pairwise combinations of DOR genes fails to reveal any overlap in gene expression, suggesting that each olfactory neuron expresses one or a small number of receptor genes and is therefore functionally distinct. How is activation of such a subpopulation of olfactory receptor neurons in the periphery sensed by the brain? In the mouse, all neurons expressing a given receptor project with precision to two of 1800 olfactory bulb glomeruli, creating a spatial map of odor quality in the brain. We have employed DOR promoter transgenes that recapitulate expression of endogenous receptor to visualize the projections of individual populations of receptor neurons to subsets of the 43 glomeruli in the Drosophila antennal lobe. The results suggest functional conservation in the logic of olfactory discrimination from insects to mammals.
Introduction
The olfactory sensory system permits animals to recognize and discriminate between a broad spectrum of volatile chemicals in the environment. Olfactory perception translates abstract chemical features of the odorous ligand into meaningful neural information, eliciting appropriate behavioral responses (Shepherd, 1994
; Buck, 1996). The relative attractiveness or repulsiveness of an odorant is highly species-specific, and can be further modulated by experience. The initial events in odor recognition are mediated by specialized bipolar olfactory sensory neurons with ciliated or microvillar dendrites that are exposed to the exterior olfactory environment. The olfactory neuron extends a single axon to the central nervous system, where it forms synapses with second-order projection neurons (Shepherd, 1994; Stocker, 1994; Buck, 1996). In arthropods and mammals, the first olfactory synapse is organized into glomeruli, spherical synaptic specializations composed of afferent olfactory neuron axons and projection neuron dendrites (Hildebrand and Shepherd, 1997).
For insects, olfaction is an important sensory modality in locating food sources, identifying appropriate sites for oviposition, selecting mates and avoiding predators. The fruit fly, Drosophila melanogaster, is a powerful model organism for the investigation of mechanisms in odor coding because it has an olfactory system that is anatomically similar to but simpler than that of vertebrates. Drosophila has the additional advantage that it can be manipulated genetically, the sequence of its euchromatic genome has been completed, the development and anatomy of its olfactory system are well characterized, and simple behavior paradigms have been developed to test olfactory perception (Siddiqi, 1987; Tully, 1987; Carlson, 1996; Adams et al., 2000).
Identification of the family of Drosophila odorant receptor (DOR) genes
In diverse species, a large family of odorant receptor genes, each encoding a different seven-transmembrane domain G protein-coupled receptor, mediates molecular recognition of thousands of distinct odorants. The first candidate odorant receptor genes were identified in the rat by a degenerate polymerase chain reaction approach using primers capable of identifying members of the G protein-coupled receptor superfamily (Buck and Axel, 1991). Mammalian odorant receptor genes are a distinct, extremely large subfamily of this receptor superfamily which couple to G proteins and transduce signals across cellular membranes. Subsequently, odorant receptor genes were identified in other mammals, fish and birds using homology-based approaches with the rat sequences as a reference point (Ngai et al., 1993; Ben-Arie et al., 1994; Nef et al., 1996; Mombaerts, 1999).
Caenorhabditis elegans chemosensory receptor genes also encode seven-transmembrane domain proteins, but these have no primary sequence identity with the vertebrate odorant receptors. Nematode odorant receptor genes were identified by molecular genetic analysis of chemosensory mutants and searching of C. elegans genome sequence databases for novel seven-transmembrane domain proteins (Troemel et al., 1995; Sengupta et al., 1996).
In both vertebrates and in nematodes, odorant receptor genes have the following properties: (i) they encode G protein-coupled seven-transmembrane domain receptors; (ii) they are selectively expressed in olfactory receptor neurons; and (iii) in each species they constitute a very large gene family of 100–1000 odorant receptors, and these are often linked in large arrays in the genome.
Candidate DOR genes were identified by a combination of difference cloning (Vosshall et al., 1999) and analysis of Drosophila genomic sequence databases (Clyne et al., 1999b; Gao and Chess, 1999; Vosshall et al., 1999). An extensive screen for genes selectively expressed in adult olfactory sensory organs (the antenna and maxillary palp) yielded a single clone [DOR104; recently renamed Or85e (Drosophila Odorant Receptor Nomenclature Committee, 2000)] that encodes a putative odorant receptor, with seven transmembrane domains and no homology to any known gene. Or85e was found to be expressed in 20 of the 120 olfactory neurons of the maxillary palp (Vosshall et al., 1999). Attempts to identify additional members of the DOR gene family by conventional molecular biology techniques that would yield either physically linked or closely related genes to Or85e were unsuccessful. However, analysis of Drosophila genome databases by our group and others revealed 18 additional genes with significant sequence relatedness to Or85e, many of which are selectively expressed in olfactory receptor neurons in the adult fly (Clyne et al., 1999b; Gao and Chess, 1999; Vosshall et al., 1999). The completion of the euchromatic genome sequence has permitted an analysis of the complete repertoire of DOR genes. The fly genome has a total of 60 genes with homology to the DOR gene family (Table 1) (Adams et al., 2000; Drosophila Odorant Receptor Nomenclature Committee, 2000; Rubin et al., 2000; Vosshall et al., 2000). Although these genes are extremely divergent, sharing on average only 20% amino acid identity, conserved sequences in the putative seventh transmembrane domain are a signature of this family and these are found in all 60 DOR genes.
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Although odorant receptors in these diverse species share a common function and secondary structure, there is no primary sequence identity between the odorant receptor genes of nematodes, flies and vertebrates, reflecting an apparently independent evolutionary origin (Vosshall et al., 1999
). There is also a wide variation in the number of odorant receptor genes in a given species. Nematodes and mammals have a repertoire of 1000 receptor genes, while fish, birds and flies have 100 genes (Mombaerts, 1999). The relatively small repertoire of odorant receptor genes in the fly may reflect the ecological specialization of this insect, which feeds largely on yeast that grows on rotting fruit. It will be of interest to examine the repertoire of odorant receptor genes in an insect, such as the honeybee, which possesses a more elaborate olfactory sensory system and perceives a wider variety of odorants. The spatial organization of DOR gene expression in the antenna and maxillary palp
Adult fruit flies have 1300 olfactory receptor neurons, distributed between the third antennal segment (1180 neurons) and the more ventrally located maxillary palp (120 neurons). Each DOR gene is expressed in a small subset of olfactory neurons in either the antenna or the maxillary palp (Table 1; Figure 1) (Clyne et al., 1999b; Gao and Chess, 1999; Vosshall et al., 1999, 2000). Double labeling with markers that label Drosophila neurons confirmed that the cells expressing DOR genes are indeed olfactory receptor neurons (Vosshall et al., 1999). While the average DOR gene is expressed in 20 olfactory neurons, some receptors are expressed in only 2–3 neurons (Or33a, Or49b), while Or47b is expressed in >50 neurons. Seven DOR genes are found solely in the maxillary palp, where they appear randomly interspersed but non-overlapping in expression (Vosshall et al., 2000).
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In the antenna, the expression of DOR genes is highly stereotyped, with each gene labeling a conserved subset of neurons. In situ hybridization with the linked genes Or65b and Or65c (Figure 1) reveals that these genes are expressed in non-overlapping domains in the ventral-lateral and ventral-medial antenna, respectively. The relative position of neurons expressing a given receptor is conserved between individual flies and is not sexually dimorphic. A total of 35 DOR genes are expressed in the adult antenna (Table 1) (Vosshall et al., 2000
).
The expression of 17 DOR genes is not detected in either organ, or in any other tissue in the adult fly. These may be expressed at low levels in the olfactory system and are therefore not detectable by conventional in situ hybridization methods. Alternatively, they may be expressed in a tissue or at a developmental time point that has not been examined in these studies. Neither these 17 nor any other DOR genes were found to be expressed in the larval chemosensory system, nor in the gustatory system of the larva or adult (Vosshall et al., 1999, 2000). DOR genes are therefore likely to mediate recognition of volatile olfactory stimuli. A family of genes encoding novel seven-transmembrane domain G protein-coupled receptors distinct from the DOR genes has been proposed as candidate taste receptors in the fly (Clyne et al., 2000).
Olfactory neurons express one DOR gene and the ubiquitous odorant receptor Or83b
In the mouse, each olfactory receptor neuron is likely to express only a single odorant receptor gene of the 1000 possible odorant receptors in the mouse genome, making that neuron functionally distinct (Chess et al., 1994; Malnic et al., 1999). Neurons expressing a given receptor are scattered at random across the olfactory sensory epithelium, but converge to a single glomerulus on each side of the olfactory bulb in the brain (Ressler et al., 1994; Vassar et al., 1994; Mombaerts et al., 1996). Therefore activation of a given odorant receptor is sensed in the brain by the activation of all cells expressing this receptor.
In contrast, the nematode C. elegans uses a different logic of odor coding. Each of the 16 pairs of chemosensory neurons probably expresses up to 20 odorant receptors (Bargmann and Horvitz, 1991; Troemel et al., 1995). Activation of any one of the odorant receptors expressed in a neuron will produce a stereotyped behavior that is the property of the neuron that is activated, not the identity of the particular activated odorant receptor (Troemel et al., 1997).
Examination of the number of odorant receptor genes expressed per neuron in Drosophila suggests that the fruit fly olfactory system more closely resembles that of the mouse. Olfactory neurons in Drosophila are likely to express only a single DOR gene. There are 120 olfactory neurons in the maxillary palp, and each of seven receptors expressed in this organ labels 20 neurons. Double-label in situ hybridization experiments with three of these seven genes (Or46a, Or59c and Or85e) demonstrated that each receptor is expressed in distinct, non-overlapping subset of neurons in the maxillary palp (Vosshall et al., 2000). Similar experiments that examined the expression of 15 antennal DOR genes failed to show co-expression of any two DOR genes in the same neuron (Vosshall et al., 1999, 2000). It is therefore likely that a given olfactory neuron in Drosophila expresses only a single DOR gene.
A notable exception to this conclusion is a single odorant receptor, Or83b, which is expressed in all olfactory neurons throughout the life cycle of Drosophila (Vosshall et al., 1999, 2000). The function of this non-canonical odorant receptor gene is unknown. Similarly broad expression has been observed for two goldfish odorant receptors, which are expressed in >50% of olfactory neurons in this animal (Speca et al., 1999). In the fly, the ubiquitous odorant receptor may act as a co-receptor by heterodimerizing and altering the ligand specificity of conventional DOR genes, as has been suggested for other G protein-coupled receptors (Jordan and Devi, 1999; Rocheville et al., 2000). Alternatively, it may be required for functional assembly and dendritic targeting of conventional odorant receptors, as seen with the association of two GABAB subunits into a functional receptor (Jones et al., 1998; Kaupmann et al., 1998; White et al., 1998). Analysis of mutations in the Or83b gene will provide insights into its function in the olfactory system of Drosophila.
An olfactory sensory map in the antennal lobe
How does the brain sense the activation of a distinct subset of olfactory receptor neurons? In the mouse, neurons expressing a given receptor extend axons that synapse with one or two glomeruli in the olfactory bulb of the brain (Ressler et al., 1994; Vassar, et al., 1994; Mombaerts et al., 1996). Therefore neurons expressing one of the 1000 possible odorant receptors are precisely wired to two of 1800 glomeruli in each olfactory bulb. This convergent wiring scheme simplifies the discrimination of olfactory stimuli: the activation of neurons expressing a given receptor is sensed in the brain by the activation of a specific glomerulus. This may form the basis of an olfactory code that is interpreted by higher brain centers to produce the qualitative experience of the odor.
The antennal lobe, the olfactory bulb equivalent of the fly, possesses 43 glomeruli and receives input from the 1300 olfactory neurons of the antenna and maxillary palp (Stocker, 1994; Laissue et al., 1999). The number of DOR genes detectably expressed in adult olfactory neurons (42) approximates the number of glomeruli (43). This would suggest a convergent organization of projections similar to that seen in the mouse olfactory system. We and others have used genetic labeling techniques to show that all neurons expressing a given receptor indeed converge upon one or two antennal lobe glomeruli (Gao et al., 2000; Vosshall et al., 2000) (Figures 2 and 3). In these experiments, 2–8 kb of DNA upstream of the coding region of five DOR genes were fused to the yeast transcription factor Gal4 (Vosshall et al., 1999, 2000). These promoter fusion constructs give robust expression that recapitulates the number and spatial distribution of neurons expressing the endogenous DOR gene (Vosshall et al., 1999, 2000). Olfactory neuron projections were examined in animals transgenic for both the DOR–Gal4 transgene and a transgene expressing a C-terminal fusion of Green Fluorescent Protein (GFP) to the synaptic vesicle protein, n-synaptobrevin (UAS–nsyb–GFP) (Estes et al., 2000). This fusion protein accumulates at axon terminals and permits the resolution of single axons as they enter the antennal lobe (Estes et al., 1997; Ito et al., 1998). All neurons expressing either Or47b (Figure 2), Or22a (Figure 3) or Or47a (data not shown) each converge upon a single glomerulus in the antennal lobe (Vosshall et al., 2000). The position and size of these glomeruli is invariant between individuals and not sexually dimorphic. Convergence to a single ventral antennal lobe glomerulus is seen for all cells expressing Or46a, a maxillary palp receptor (Vosshall et al., 2000). In contrast, Or23a-expressing neurons synapse with two glomeruli in the antennal lobe (Gao et al., 2000; Vosshall et al., 2000).
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These results suggest that there is a spatial map encoding odor quality in the antennal lobe of the Drosophila brain. Functional imaging of glomerular activation in diverse species is in accord with this model of convergent olfactory coding. In the honeybee, moth, fish, rat and salamander, a given odorant elicits activation of a small, spatially invariant subset of glomeruli that is conserved between different individuals (Kauer et al., 1987
; Hansson et al., 1992; Friedrich and Korsching, 1997; Galizia et al., 1999; Rubin and Katz, 1999; Sachse et al., 1999). Although both molecular convergence and spatial patterns of glomerular activation are well described, whether the brain uses this convergence in odor coding is controversial (Laurent, 1997, 1999). The genetic manipulability of Drosophila, coupled with the small number and unambiguously identifiable glomeruli, should allow a functional test of the relevance of spatial coding in the antennal lobe for olfactory perception. Conclusion and future directions
The identification of insect odorant receptors has provided initial insight into the molecular logic of olfaction in Drosophila. There are 60 DOR genes, 42 of which are detectably expressed in subsets of neurons in the antenna or maxillary palp and one of which is expressed in all olfactory neurons. Olfactory neurons are likely to express only one of the conventional DOR genes in addition to the ubiquitous odorant receptor Or83b. All neurons expressing a given receptor extend axons that form synapses with one or two of the 43 antennal lobe glomeruli. A similar convergence is observed in the mouse olfactory system (Ressler et al., 1994; Vassar et al., 1994; Mombaerts et al., 1996). Therefore in both the fly and the mouse, odorant receptor gene expression is correlated with neuronal functional specificity.
What is the evidence that the DOR genes indeed encode the ligand-binding odorant receptors in Drosophila? DOR genes, like odorant receptors in other species (Mombaerts, 1999), are predicted to encode G protein-coupled receptors with seven transmembrane domains (Clyne et al., 1999b; Gao and Chess, 1999; Vosshall et al., 1999, 2000). The expression of DOR genes is restricted to olfactory neurons of the adult fly (Clyne et al., 1999b; Gao and Chess, 1999; Vosshall et al., 1999, 2000), and the spatial patterns of expression approximate the number and distribution of different functional types of neurons in the antenna and maxillary palp defined by electrophysiology (Siddiqi, 1987; de Bruyne et al., 1999). The acj6 mutant displays both altered chemical specificity of individual identified neurons and alterations in DOR gene expression (Clyne et al., 1999a). DOR–GFP fusion proteins are localized to dendrites, the site of interaction of odorous ligand with the odorant receptor (L.B. Vosshall and R. Axel, unpublished data). The current evidence is largely circumstantial and definitive proof that these are functional odorant receptors awaits experiments that demonstrate binding of odorous ligands to this family of receptors.
Further understanding of the molecular basis of olfactory coding in insects will require associating receptors with specific ligands. Electrophysiological experiments have provided an initial glimpse into the peripheral odor code in adult flies. Single sensillum recordings have defined six functional classes of neurons in the maxillary palp, whose ligand specificity is narrowly defined (Clyne et al., 1999a; de Bruyne et al., 1999). The number of functional classes in the antenna is considerably larger and the spatial distribution of these sensilla corresponds well to the map of odorant receptor gene expression (Siddiqi, 1987; Clyne et al., 1997). The next step will be to match these functional classes of neurons with the particular DOR genes that they express, and the glomerulus in the brain which these neurons innervate. Combining this analysis with functional imaging that can resolve the activation of individual glomeruli in response to odorous ligands will be of interest (Friedrich and Korsching, 1997; Galizia et al., 1999; Rubin and Katz, 1999; Sachse et al., 1999).
These spatial maps in the peripheral olfactory system and in the antennal lobe are ultimately decoded by higher brain centers, allowing the animal to experience the quality of the odor. Olfactory information is relayed via antennal lobe projection neurons to both the mushroom body and the lateral horn of the protocerebrum (Stocker, 1994; Ito et al., 1998). The circuits involved in this process of decoding are poorly understand in all animals but the prospects for understanding higher level olfactory coding in the fruit fly are good: these insects respond to a restricted subset of odorants, and have a limited olfactory receptor repertoire and a relatively small number of glomeruli. The application of genetics, electrophysiology and imaging to this problem promise to yield answers in the short term.
Acknowledgments
The author’s research is supported by grants from the Howard Hughes Medical Institute and the National Institutes of Health (NIMH:5P50 MH50733-6) to Richard Axel.
References
Adams, M.D., Celniker, S.E., Holt, R.A., Evans, C.A., Gocayne, J.D., Amanatides, P.G. et al. (2000) The Genome Sequence of Drosophila melanogaster. Science, 287, 2185–2196.
Bargmann, C.I. and Horvitz, H.R. (1991) Chemosensory neurons with overlapping functions direct chemotaxis to multiple chemicals in C. elegans. Neuron, 7, 729–742.[Web of Science][Medline]
Ben-Arie, N., Lancet, D., Taylor, C., Khen, M., Walker, N., Ledbetter, D.H. et al. (1994) Olfactory receptor gene cluster on human chromosome 17: possible duplication of an ancestral receptor repertoire. Hum. Mol. Genet., 3, 229–235.
Buck, L.B. (1996) Information coding in the vertebrate olfactory system. Annu. Rev. Neurosci., 19, 517–544.[Web of Science][Medline]
Buck, L. and Axel, R. (1991) A novel multigene family may encode odorant receptors: a molecular basis for odor recognition. Cell, 65, 175–187.[Web of Science][Medline]
Carlson, J.R. (1996) Olfaction in Drosophila: from odor to behavior. Trends Genet., 12, 175–180.[Web of Science][Medline]
Chess, A., Simon, I., Cedar, H. and Axel, R. (1994) Allelic inactivation regulates olfactory receptor gene expression. Cell, 78, 823–834.[Web of Science][Medline]
Clyne, P., Grant, A., O’Connell, R. and Carlson, J.R. (1997) Odorant response of individual sensilla on the Drosophila antenna. Invert. Neurosci., 3, 127–135.[Medline]
Clyne, P.J., Certel, S.J., de Bruyne, M., Zaslavsky, L., Johnson, W.A. and Carlson, J.R. (1999a) The odor specificities of a subset of olfactory receptor neurons are governed by Acj6, a POU-domain transcription factor. Neuron, 22, 339–347.[Web of Science][Medline]
Clyne, P.J., Warr, C.G., Freeman, M.R., Lessing, D., Kim, J. and Carlson, J.R. (1999b) A novel family of divergent seven-transmembrane proteins: candidate odorant receptors in Drosophila. Neuron, 22, 327–338.[Web of Science][Medline]
Clyne, P.J., Warr, C.G. and Carlson, J.R. (2000) Candidate taste receptors in Drosophila. Science, 287, 1830–1834.
Drosophila Odorant Receptor Nomenclature Committee (2000) A unified nomenclature system for the Drosophila odorant receptors. Cell, 102, 145–146.[Web of Science][Medline]
de Bruyne, M., Clyne, P.J. and Carlson, J.R. (1999) Odor coding in a model olfactory organ: the Drosophila maxillary palp. J. Neurosci., 19, 4520–4532.
Estes, P.S., Ho, G., Sandstrom, D.J. and Ramaswami, M. (1997) Development of GFP as an in vivo marker for Drosophila synapses. Soc. Neurosci. Abstr., 23, 357.
Estes, P.E., Ho, G., Narayanan, R. and Ramaswami, M. (2000) Synaptic localization and restricted diffusion of a Drosophila neuronal synaptobrevin—green fluorescent protein chimera in vivo. J. Neurogenet., 13, 233–255.[Web of Science][Medline]
Friedrich, R.W. and Korsching, S.I. (1997) Combinatorial and chemotopic odorant coding in the zebrafish olfactory bulb visualized by optical imaging. Neuron, 18, 737–752.[Web of Science][Medline]
Galizia, C.G., Sachse, S., Rappert, A. and Menzel, R. (1999) The glomerular code for odor representation is species specific in the honeybee Apis mellifera. Nature Neurosci., 2, 473–478.[Web of Science][Medline]
Gao, Q. and Chess, A. (1999) Identification of candidate Drosophila olfactory receptors from genomic DNA sequence. Genomics, 60, 31–39.[Web of Science][Medline]
Gao, Q., Yuan, B. and Chess, A. (2000) Convergent projections of Drosophila olfactory neurons to specific glomeruli in the antennal lobe. Nature Neurosci., 3, 780–785.[Web of Science][Medline]
Hansson, B.S., Ljungberg, H., Hallberg, E. and Löfstedt, C. (1992) Functional specialization of olfactory glomeruli in a moth. Science, 256, 1313–1315.
Hildebrand, J.G. and Shepherd, G.M. (1997) Mechanisms of olfactory discrimination: converging evidence for common principles across phyla. Annu. Rev. Neurosci., 20, 595–631.[Web of Science][Medline]
Ito, K., Suzuki, K., Estes, P., Ramaswami, M., Yamamoto, D. and Strausfeld, N.J. (1998) The organization of extrinsic neurons and their implications in the functional roles of the mushroom bodies in Drosophila melanogaster Meigen. Learn Mem., 5, 52–77.
Jones, K.A., Borowsky, B., Tamm, J.A., Craig, D.A., Durkin, M.M., Dai, M. et al. (1998) GABA(B) receptors function as a heteromeric assembly of the subunits GABA(B)R1 and GABA(B)R2. Nature, 396, 674–679.[Medline]
Jordan, B.A. and Devi, L.A. (1999) G-protein-coupled receptor heterodimerization modulates receptor function. Nature, 399, 697–700.[Medline]
Kauer, J.S., Senseman, D.M. and Cohen, L.B. (1987) Odor-elicited activity monitored simultaneously from 124 regions of the salamander olfactory bulb using a voltage-sensitive dye. Brain Res., 418, 255–261.[Web of Science][Medline]
Kaupmann, K., Malitschek, B., Schuler, V., Heid, J., Froestl, W., Beck, P. et al. (1998) GABA(B)-receptor subtypes assemble into functional heteromeric complexes. Nature, 396, 683–687.[Medline]
Laissue, P.P., Reiter, C., Hiesinger, P.R., Halter, S., Fischbach, K.F. and Stocker, R.F. (1999) Three-dimensional reconstruction of the antennal lobe in Drosophila melanogaster. J. Comp. Neurol., 405, 543–552.[Web of Science][Medline]
Laurent, G. (1997) Olfactory processing: maps, time and codes. Curr. Opin. Neurobiol., 7, 547–553.[Web of Science][Medline]
Laurent, G. (1999) A systems perspective on early olfactory coding. Science, 286, 723–728.
Malnic, B., Hirono, J., Sato, T. and Buck, L.B. (1999) Combinatorial receptor codes for odors. Cell, 96, 713–723.[Web of Science][Medline]
Mombaerts, P. (1999) Seven-transmembrane proteins as odorant and chemosensory receptors. Science, 286, 707–711.
Mombaerts, P., Wang, F., Dulac, C., Chao, S.K., Nemes, A., Mendelsohn, M., Edmondson, J. and Axel, R. (1996) Visualizing an olfactory sensory map. Cell, 87, 675–686.[Web of Science][Medline]
Nef, S., Allaman, I., Fiumelli, H., De Castro, E. and Nef, P. (1996) Olfaction in birds: differential embryonic expression of nine putative odorant receptor genes in the avian olfactory system. Mech. Dev., 55, 65–77.[Web of Science][Medline]
Ngai, J., Dowling, M.M., Buck, L., Axel, R. and Chess, A. (1993) The family of genes encoding odorant receptors in the channel catfish. Cell, 72, 657–666.[Web of Science][Medline]
Ressler, K.J., Sullivan, S.L. and Buck, L.B. (1994) Information coding in the olfactory system: evidence for a stereotyped and highly organized epitope map in the olfactory bulb. Cell, 79, 1245–1255.[Web of Science][Medline]
Rocheville, M., Lange, D.C., Kumar, U., Patel, S.C., Patel, R.C. and Patel, Y.C. (2000) Receptors for dopamine and somatostatin: formation of hetero-oligomers with enhanced functional activity. Science, 288, 154–157.
Rubin, B.D. and Katz, L.C. (1999) Optical imaging of odorant representations in the mammalian olfactory bulb. Neuron, 23, 499–511.[Web of Science][Medline]
Rubin, G.M., Yandell, M.D., Wortman, J.R., Gabor Miklos, G.L., Nelson, C.R., Hariharan, I.K. et al. (2000) Comparative genomics of the eukaryotes. Science, 287, 2204–2216.
Sachse, S., Rappert, A. and Galizia, C.G. (1999) The spatial representation of chemical structures in the antennal lobe of honeybees: steps towards the olfactory code. Eur. J. Neurosci., 11, 3970–3982.[Web of Science][Medline]
Sengupta, P., Chou, J.H. and Bargmann, C.I. (1996) odr-10 encodes a seven transmembrane domain olfactory receptor required for responses to the odorant diacetyl. Cell, 84, 899–909.[Web of Science][Medline]
Shepherd, G.M. (1994) Discrimination of molecular signals by the olfactory receptor neuron. Neuron, 13, 771–790.[Web of Science][Medline]
Siddiqi, O. (1987) Neurogenetics of olfaction in Drosophila melanogaster. Trends Genet., 3, 137–142.
Speca, D.J., Lin, D.M., Sorensen, P.W., Isacoff, E.Y., Ngai, J. and Dittman, A.H. (1999) Functional identification of a goldfish odorant receptor. Neuron, 23, 487–498.[Web of Science][Medline]
Stocker, R.F. (1994) The organization of the chemosensory system in Drosophila melanogaster: a review. Cell Tissue. Res., 275, 3–26.[Web of Science][Medline]
Troemel, E.R., Chou, J.H., Dwyer, N.D., Colbert, H.A. and Bargmann, C.I. (1995) Divergent seven transmembrane receptors are candidate chemosensory receptors in C. elegans. Cell, 83, 207–218.[Web of Science][Medline]
Troemel, E.R., Kimmel, B.E. and Bargmann, C.I. (1997) Reprogramming chemotaxis responses: sensory neurons define olfactory preferences in C. elegans. Cell, 91, 161–169.[Web of Science][Medline]
Tully, T. (1987) Drosophila learning and memory revisited. Trends. Neural Sci., 10, 330–335.
Vassar, R., Chao, S.K., Sitcheran, R., Nunez, J.M., Vosshall, L.B. and Axel, R. (1994) Topographic organization of sensory projections to the olfactory bulb. Cell, 79, 981–991.[Web of Science][Medline]
Vosshall, L.B., Amrein, H., Morozov, P.S., Rzhetsky, A. and Axel, R. (1999) A spatial map of olfactory receptor expression in the Drosophila antenna. Cell, 96, 725–736.[Web of Science][Medline]
Vosshall, L.B., Wong, A.M. and Axel, R. (2000) An olfactory sensory map in the fly brain. Cell, 102, 147–159.[Web of Science][Medline]
White, J.H., Wise, A., Main, M.J., Green, A., Fraser, N.J., Disney, G.H., Barnes, A.A., Emson, P., Foord, S.M. and Marshall, F.H. (1998) Heterodimerization is required for the formation of a functional GABA(B) receptor. Nature, 396, 679–682.[Medline]
Accepted October 31, 2000
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W. L. Roelofs and A. P. Rooney Molecular genetics and evolution of pheromone biosynthesis in Lepidoptera PNAS, August 5, 2003; 100(16): 9179 - 9184. [Abstract] [Full Text] [PDF]
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 I. Ganguly, T. F. C. Mackay, and R. R. H. Anholt Scribble Is Essential for Olfactory Behavior in Drosophila melanogaster Genetics, August 1, 2003; 164(4): 1447 - 1457. [Abstract] [Full Text] [PDF]
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 S. Scherer, R. F. Stocker, and B. Gerber Olfactory Learning in Individually Assayed Drosophila Larvae Learn. Mem., May 1, 2003; 10(3): 217 - 225. [Abstract] [Full Text] [PDF]
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 M. C. Stensmyr, E. Giordano, A. Balloi, A.-M. Angioy, and B. S. Hansson Novel natural ligands for Drosophila olfactory receptor neurones J. Exp. Biol., February 15, 2003; 206(4): 715 - 724. [Abstract] [Full Text] [PDF]
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 D. S. Hekmat-Scafe, C. R. Scafe, A. J. McKinney, and M. A. Tanouye Genome-Wide Analysis of the Odorant-Binding Protein Gene Family in Drosophila melanogaster Genome Res., September 1, 2002; 12(9): 1357 - 1369. [Abstract] [Full Text] [PDF]
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R. G. Vogt, M. E. Rogers, M.-d. Franco, and M. Sun A comparative study of odorant binding protein genes: differential expression of the PBP1-GOBP2 gene cluster in Manduca sexta (Lepidoptera) and the organization of OBP genes in Drosophila melanogaster (Diptera) J. Exp. Biol., March 15, 2002; 205(6): 719 - 744. [Abstract] [Full Text] [PDF]
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