Grant: Joint Canada-Israel Health Research Program

The connections inside the brain need to be wired in a precise manner during development in order to ensure its proper function. Indeed, improper wiring of the nervous system has been suggested to be the basis for some neurodevelopmental defects. What are the mechanisms that guarantee the proper wiring between the billions of neurons during brain development? Axons are guided to their targets by molecules in the extracellular environment called "guidance cues." Guidance cues activate receptors that reside on axons, which trigger signaling cascades that modulate the cytoskeleton and steer the axons in the right direction. These cues can be either attractive, pulling axons in the right direction; or repulsive, preventing axons from navigating to incorrect targets. Other conditions in which axons need to navigate in adults are regeneration after mechanical or degenerative stimuli, as after spinal cord injury. Proper regeneration in adult mammals is still a significant clinical problem. In this proposed research plan, we will investigate the mechanism of local protein translation at the tip of the axons that allow them to properly respond to guidance cues in their journey to their targets. In addition, we will examine the role of this developmental mechanism in axon regeneration after injury. Overall, this work will shed new light on the mechanisms that govern the wiring of the nervous system and their role in axon regeneration.