How are the extraordinarily precise connection patterns established in the brain? The Drosophila olfactory system provides an excellent system to identify determinants of connection specificity due to the availability of numerous markers for odorant receptors neuron (ORN) target specificity and genetic reagents for manipulating ORN and target development. We performed a large-scale forward genetic screen to identify mutations that disrupt the stereotypical pattern of OR connections. We isolated approximately 50 mutant lines exhibiting neuronal mistargeting phenotypes. One of the mutations disrupts a micro RNA, mir-279. Loss of mir-279 function in the olfactory system generates a hybrid neuron that acquires wiring properties of two ORN classes (Or59c and GR21a). I propose to pursue the analysis of defects found in mir-279 mutant, in an effort to dissect out the mechanisms regulating targeting of different classes of ORNs. The analysis will involve genetic and phenotypic characterization and rescue of ORN targeting and receptor misexpression defects, as well as determination of expression pattern of mir-279. Subsequently, molecular and genetic approaches will be taken to identify mir-279 targets functioning in olfactory wiring specificity.
