The Drosophila olfactory system presents a great opportunity to understand the general principles of wiring specificity, and how the wiring of neuronal circuits contributes to olfaction. In the Drosophila olfactory system, second order projection neurons (PNs) innervate specific glomeruli in the antennal lobe. We are exploring the molecular mechanisms by which PNs target their dendrites to specific glomeruli. Longitudinals lacking (lola) is a Zn-finger transcription factor identified as a putative regulator of axon guidance that splices to at least 20 unique isoforms. This proposal will further investigate the function of individual Lola isoforms in PN wiring specificity. The lola locus may prove a useful model to demonstrate the function of molecular diversity at the transcriptional level in wiring specificity. Specifically, I will 1. Perform a systematic expression analysis of individual lola isoforms in the AL using isoform specific RNA in-situ hybridization and immunostaining. 2. Generate new isoform-specific mutants for those isoforms expressed in PNs using homologous recombination, and test their function in PN wiring using MARCM analysis. 3. Generate isoform-specific UAS transgenes to test their ability to rescue isoform-specific mutants using MARCM mediated overexpression.
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