In the developing embryo, growing nerves have to navigate long distances to find their targets and to connect up the nervous system. The individual fibers of the nerves are known as axons, and understanding how axons navigate is of great interest as it explains how the initial complexity of the brain and nervous system arises. Growing axons respond to cues in their environment that can either be attractive or repulsive; the same cues can also stimulate overall growth. The Down Syndrome Cell Adhesion Molecule (Dscam) gene is present in most organisms with a nervous system. Dscam unexpectedly allows axons to detect well-known navigational cues and to respond to them. The working model that drives much of the work in this proposal is that Dscam interprets the cues as attractive signals and stimulates axon growth towards the cues. This model is being tested in the fruit fly Drosophila using a genetic approach. The fruit fly nervous system is simple enough to observe the growth of single axons and to analyze how axons are affected when Dscam activity is reduced or absent. The results from the experiments will allow evaluation of whether all or part of the model is correct. The work is supported by experiments on tissue culture cells examining how Dscam and the cues physically interact. The project provides state of the art genetic and molecular biology training for both graduate and undergraduate students. The results derived from this study are expected to advance our knowledge of how axons grow and navigate in the fruit fly, as well as in many other nervous systems including the vertebrate spinal cord.
