NF-kappaB signaling and photoreceptor axon guidance in Drosophila melanogaster

During development of the visual system of Drosophila melanogaster , growth cones at the tips of advancing photoreceptor axons respond to instructive cues in the environment and are guided toward appropriate synaptic partners within the optic lobe of the brain. Research has focused on the identification of these molecular cues, their receptors and the signaling processes that mediate their function. This thesis describes the Drosophila line GSd447, which possesses a P element that can support GAL4-mediated transcriptional activation of a gene near the site of insertion. GAL4-driven misexpression of GSd447 in the eye disc causes the R1-R6 photoreceptor axons to be mistargeted. The mistargeted R1-R6 axons fail to terminate in the lamina, and project to a deeper layer in the medulla of the optic lobe. To identify the gene(s) causing these axon targeting defects, two different approaches were used; a candidate gene analysis using UAS-transgenes, and a chemical mutagenesis screen to suppress the mistargeting defects caused by GSd447. Both approaches strongly suggested the NF-kappaB transcription factor, Dorsal, was responsible for the axon targeting defects. In addition, a mutation of cactus, which encodes the inhibitor of Dorsal, was found to genetically interact with GSd447 misexpression to enhance the observed axon targeting defects. Both dorsal and cactus are expressed in photoreceptor cell bodies. Studies of dorsal mutants revealed moderate axon targeting defects using the dorsal alleles identified in the suppression screen. No defects have been found to date in cactus mutants, but severe loss-of-function cactus alleles have not yet been tested. Together, these results and recent studies by others provide evidence for an important role for components of the NF-kappaB signaling pathway in the development of the nervous system in both vertebrates and invertebrates