How nervous systems are assembled and properly wired during development remains a major question in biology. At the central nervous system (CNS) midline of all organisms with bilateral symmetry, neurons make the decision to cross or not to cross from one side of the midline to the other. The CNS midline has served as a model for the molecular genetic dissection of axon guidance mechanisms. Several signaling pathways have been identified that regulate this behavior of axons at the CNS midline, including the Slit-Robo signaling pathway. This pathway is highly conserved and functions in organisms ranging from worms to humans. While this core signaling pathway is highly conserved, the regulation of Slit-Robo signaling varies in different organisms. In the fruit fly, Drosophila, the Commissureless (Comm) protein is a key regulator of Slit-Robo signaling. Comm functions by regulating the sub-cellular distribution of the Robo receptor. While Comm is essential for proper CNS development in Drosophila, Comm-like genes are not found outside of insects. By examining the sequenced genomes of diverse insects, Dr. Seeger and his colleagues have found that Comm-like genes are present in only a subset of insects. Dr. Seeger will test the hypothesis that Comm-like genes in mosquitoes and body lice regulate Robo receptor distribution as in Drosophila. They will also address how Slit-Robo signaling is regulated in insects that lack a Comm-like gene, like beetles and wasps. What will emerge from these studies is a better understanding of the mechanisms that regulate the Robo-Slit signaling pathway as well as insights into the evolution of axon guidance mechanisms. Finally, these studies will provide extensive research experiences in molecular genetics, cell biology, and developmental neuroscience for numerous undergraduates and several graduate students within the Seeger laboratory, helping to provide hands-on training for our next generation of scientists.
