Dissecting a Role of Caspases in Axon Guidance: A Genetic Approach

One of the primary mechanisms through which the developing nervous system organizes itself is known as axon guidance. In axon guidance, the axon of a growing neuron takes signaling cues from the environment to change direction on the way to its target. Guidance molecules such as netrin and slit guide growing axons towards a target. After the guidance molecules bind the cell surface receptors, a poorly understood cascade occurs which ultimately results in the cytoskeleton of the axon rearranging to allow a change in direction. This thesis proposes that the change in direction an axon undergoes after receiving guidance cues is caused by caspases (proteins known for destroying other proteins during programmed cell death.) Using genetic manipulation of fruit flies (Drosophila Melanogaster), we were able to create several embryos with an increased level of caspase activity. Subsequent staining of the ventral nerve cords with the antibody BP102 revealed that simply changing the caspase activity in neurons had a profound effect on the guidance of the axons coming from those neurons. This indicates that caspases are at least partially responsible for altering the cytoskeleton of an axon and changing its direction of growth during normal neurodevelopment