The Roles of Wnt5 and the Drl Receptor in the Development of the Drosophila Olfactory System

113 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2009.During the development of the Drosophila olfactory system, olfactory receptor neurons expressing the same odorant receptors converge their axons precisely onto a specific set of projection neuron dendrites, forming glomeruli in stereotypic positions of the antennal lobe. Although many studies have revealed the crucial role of projection neurons in the spatial patterning of glomeruli, the potential instructive role of olfactory neurons was not well investigated in Drosophila. In a gain-of-function genetic screen, we identified wnt5 as a candidate regulatory gene for the antennal lobe development. The overexpression of wnt5 in the ingrowing olfactory neurons induces the formation of ectopic glomeruli in the antennal commissure. Conversely, the ablation of wnt5 results in the derangement of glomerular pattern in the antennal lobe. Genetic rescue and mosaic analysis indicate that the wnt5 gene is specifically expressed in a subset of olfactory neurons. The deletion of the putative Wnt5 receptor, Derailed (Drl) receptor tyrosine kinase, also leads to a severe disruption in the glomerular pattern and the formation of ectopic glomeruli in the midline, which can be rescued by glial cell-specific expression of the drl cDNA transgene. Genetic interaction reveals that the Drl receptor functions antagonistic to and upstream of the Wnt5 protein in the antennal lobe development. I proposed that Wnt5 ligand expressed from olfactory axon terminals instructs the proper targeting of these axons and the positioning of glomeruli. I also determined that Wnt5 provides a directional cue to support the precise arborization of projection neuron dendrites and that Wnt5 is essential for the formation of normal synaptic structure in glomeruli. My study proposed a novel Wnt5 signaling mechanism, in which the Drl receptor expressed on the membrane of glial cells serves to downregulate the function of Wnt5 protein.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD