Analysis of the Molecular Mechanisms of Drosophila Antennal Lobe Development

109 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2008.In Drosophila or mice, the axons of olfactory receptor neurons (ORNs) bearing the same odorant receptor converge on one specific glomerulus in the antennal lobe or olfactory bulb, where they synapse with the dendrites of the postsynaptic cells, projection neurons (PNs) or mitral cells. Mutation in derailed/drl gene, a receptor tyrosine kinase, leads to the disruption of the glomerular pattern. Antibody staining shows that Drl is located in the antennal lobe throughout the period of the development of the antennal lobe, from 16h after pupal formation (APF) to 40h APF and expressed by several types of cells including PNs, glial cells and a type of unidentified cells. Mosaic analysis demonstrates that the loss of drl function from the ORNs has no defect, while the loss of drl from the PNs results in dendritic targeting defects. In rescue experiments, where cell-type specific GAL4 drivers were used to drive Drl expression in drl null mutant background, the drl mutant phenotype is rescued by both Repo-GAL4, a glial-cell specific driver and GH146-drl, where the regulatory region of GH146-GAL4, a PN driver is directly fused to the drl cDNA. Furthermore, a truncated Drl protein containing the extracellular WIF (Wnt Inhibitory Factory) domain only is sufficient to rescue the mutant phenotype. Wnt5 has been implicated to act as a ligand for Drl receptor in Drosophila ventral nerve cord. Our genetic analyses in the antennal lobe suggest a novel mechanism for the interaction of Wnt5 and Drl. Our data suggest that Drl antagonizes Wnt5. A genetic screen for suppressors of a Wnt5 gain-of-function phenotype in the antennal lobe suggests that a Drl homolog, Doughnut, may act as a receptor to Wnt5 ligand.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD