Date of Graduation
Bachelor of Science
As the nervous system develops in animal embryos, neuronal axons are guided to their synaptic targets by extra cellular cues that signal through axon guidance receptors expressed on the surface of the axon. In animals with bilateral symmetry, one of the important decisions made by nearly every axon in the embryonic nervous system is whether to stay on its own side of the body, or to cross the midline and connect to cells on the opposite side. The Roundabout (Robo) family is an evolutionarily conserved group of axon guidance receptors that regulate midline crossing in a wide range of animal groups, by signaling midline repulsion in response to their ligand Slit. Despite their strong evolutionary conservation, it is unknown if the mechanisms of Robo signaling are conserved across different species.
Can Robo receptors from mice regulate axon guidance decisions in Drosophila embryos, or do species-specific difference exist in the cellular signaling mechanisms by which Slit and Robos regulate midline crossing? To investigate the evolutionary conservation of Robo signaling mechanisms, we are using the GAL4/UAS system in Drosophila to express Robo receptors from mice in fly neurons during embryonic development. We find that mammalian Robo receptors can repel axons from the midline in Drosophila embryos, which suggests that the mechanisms by which they signal midline repulsion are conserved in insects and mammals. However, a further study involving a GAL4/UAS rescue of mutated Drosophila Robo receptors with mouse Robo receptors indicates that mammalian Robo genes cannot successfully effect midline repulsion in fly embryos on their own. Therefore it is still uncertain how clearly the mechanisms of Robo signaling are conserved from insects to mammals.
In addition, we are creating chimeric receptor genomes combining one Drosophila Robo domain with all other domains of mouse Robo. We find that the chimeric rescue construct cannot effectively rescue Drosophila Robo mutants when expressed at normal level.
evolutionary conservation, Robo, Drosophila, axon guidance, fruit fly, midline repulsion
Loy, Allison, "Evolutionary conservation of midline repulsion by Robo family receptors in flies and mice" (2018). Biological Sciences Undergraduate Honors Theses. 24.