The organization and development of neuronal systems are problems of great importance in modern biology. This proposal concerns a molecular and genetic analysis of a chemosensory system and is designed with a view to addressing the fundamental problems of (i) the mechanisms of chemosensory transduction, (ii) the principles of chemosensory coding, and (iii) the means by which genes specify the development of a complex neuronal system. Drosophila is an excellent organism in which to address these problems, as it possesses a highly sophisticated olfactory system which may be investigated by powerful genetic and molecular means. Among a set of mutants defective in chemosensory behavior are several which respond abnormally to one chemical but which appear normal in response to other chemicals. Such mutants define genes which may play roles in chemically-specific olfactory pathways; these genes could encode olfactory receptor molecules or other products required for transduction or processing of specific types of olfactory information. A genetic and molecular analysis of one such gene, defined by the 3D18 mutation, is proposed. By characterizing the distribution within the olfactory system of products of genes which are specific to individual functional pathways, we anticipate that we may gain an enhanced understanding of the functional organization of the system, which is, in turn, critical to an understanding of how complex olfactory stimuli are encoded into a form interpretable to the brain. Genetic analysis of the olfD locus is also proposed;
we aim to determine whether olfD represents a second class of gene, required for response to all chemicals but not in other sensory modalities, such as vision. Other mutants we have isolated are defective both in visual physiology and chemosensory behavior. Relationships between chemosensory and visual transduction will be sought by determining whether the affected genes correlate with previously characterized visual system genes, and by subjecting visual mutants to chemosensory assays. The feasibility of using a direct molecular approach to isolate genes required for olfactory transduction and information processing will be assessed: we will attempt to isolate antennal- specific cDNA clones using a new method of subtractive hybridization.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM036862-04
Application #
3291445
Study Section
Neurology C Study Section (NEUC)
Project Start
1986-01-01
Project End
1993-12-31
Budget Start
1989-01-01
Budget End
1989-12-31
Support Year
4
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Yale University
Department
Type
Schools of Arts and Sciences
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
McKenna, M P; Hekmat-Scafe, D S; Gaines, P et al. (1994) Putative Drosophila pheromone-binding proteins expressed in a subregion of the olfactory system. J Biol Chem 269:16340-7
Lilly, M; Kreber, R; Ganetzky, B et al. (1994) Evidence that the Drosophila olfactory mutant smellblind defines a novel class of sodium channel mutation. Genetics 136:1087-96
Lilly, M; Riesgo-Escovar, J; Carlson, J (1994) Developmental analysis of the smellblind mutants: evidence for the role of sodium channels in Drosophila development. Dev Biol 162:1-8
Riesgo-Escovar, J R; Woodard, C; Carlson, J R (1994) Olfactory physiology in the Drosophila maxillary palp requires the visual system gene rdgB. J Comp Physiol A 175:687-93
Raha, D; Carlson, J (1994) OS9: a novel olfactory gene of Drosophila expressed in two olfactory organs. J Neurobiol 25:169-84
Carlson, J (1993) Molecular genetics of Drosophila olfaction. Ciba Found Symp 179:150-61;discussion 162-6
Lilly, M; Carlson, J (1990) smellblind: a gene required for Drosophila olfaction. Genetics 124:293-302
Monte, P; Woodard, C; Ayer, R et al. (1989) Characterization of the larval olfactory response in Drosophila and its genetic basis. Behav Genet 19:267-83
McKenna, M; Monte, P; Helfand, S L et al. (1989) A simple chemosensory response in Drosophila and the isolation of acj mutants in which it is affected. Proc Natl Acad Sci U S A 86:8118-22
Woodard, C; Huang, T; Sun, H et al. (1989) Genetic analysis of olfactory behavior in Drosophila: a new screen yields the ota mutants. Genetics 123:315-26

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