Investigation of the molecular mechanisms leading to polarized Sonic Hedgehog signal transduction in axonal growth cones

Funding Details
Canadian Institutes of Health Research
  • Grant type: CIHR Fellowship
  • Years: 2015/16 to 2016/17
  • Total Funding: $127,500
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Project Summary

Our brain and spinal cord is a very complex assembly of millions of cells that are linked to each other by specific connections. The way each neuron sends its principal projection, called the axon, to contact precisely other neurons is crucial. This network is the foundation of our cognitive, sensory and motor functions. Many neurological diseases are linked to wrong wiring of the nervous system such as autism, Down syndrome, cerebral palsy, etc. During embryonic development, axons are guided towards their final targets to form connections by sensing molecular cues in their environment, using a specialized structure at the tip of the growing axon, the growth cone. A molecule called Sonic Hedgehog (Shh) plays an important role as a guidance cue for the establishment of neural circuits. Dr. Charron and collaborators have identified the protein Boc as the receptor allowing the neuron to detect Shh in its environment. Our preliminary data indicate that upon detecting Shh, Boc relocalize to the surface of the growth cone. The goal of this project is to identify the proteins responsible for relocalizing Boc in response to Shh and the importance of this relocalization for guiding axons. To elucidate this, I will use in vitro and in vivo experimental approaches available in the lab, including innovative strategies to provide an unprecedented level of analysis of how these molecules can act on axon guidance. This will provide a better understanding of how molecular cues from the environment can control the localization of important regulators in the neuron and impart directionality on the growth cones. This mechanism is crucial to establish the correct assembly of the neural circuitry. As a final goal, these studies aim to provide important insight into defective wiring in neurodevelopmental and neuropsychiatric diseases and into the recovery from injury during regeneration.