In Drosophila and mice, olfactory receptor neurons (ORNs) expressing the same receptors have convergent axonal projections to specific glomerular targets in the antennal lobe/olfactory bulb, creating an odor map in this first olfactory structure of the CNS. Mitral/mfted cells in vertebrates and antennal lobe projection neurons (PNs) in Drosophila send dendrites into glomeruli and axons to higher brain centers to process and relay the olfactory information. We have made use of the MARCM (Mosaic Analysis with a Repressible Cell Marker) method to perform a systematic clonal analysis of Drosophila PNs, and found that PN's are prespecified by lineage and birth order to synapse with specific incoming ORN axons and therefore to carry specific olfactory information. Further, PNs possess stereotypical axon branching patterns and terminal fields in the lateral horn--one of the two central PN targets--according to glomerular class, for further processing of olfactory information in the brain. In this grant, we propose a series of experiments to explore how Drosophila PNs establish their synaptic connectivity by targeting their dendrites to specific glomeruli. We will study the cellular and developmental events of PN dendritic targeting, and identify molecules and mechanisms for PN dendritic targeting by both candidate gene approaches and a forward genetic screen making use of the MARCM method. We will also explore whether mechanisms similar to those used to specify PN dendritic targeting are also used to establish their specific axon branching patterns and terminal fields. Our unpublished preliminary studies already suggest the importance of certain transcription factor and cell surface proteins in determining PN dendritic targeting and specifying axonal patterning, and prove that a MARCM-based mosaic screen would enable us to identify new genes essential for PN dendritic targeting specificity. These studies will contribute to our understanding of a number of important neurobiological problems, including neuronal fate specification, dendritic guidance and targeting, and the logic of the assembly of the olfactory networks and neural networks in general. Our studies will also provide insight into how olfactory information is transferred and transformed along the central pathways in the brain. ? ?
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