Inflammatory control of neurogenesis and regeneration in the brain and spinal cord

Immune cells acutely provide critical inflammatory signals that are required to restrict damage and initiate recovery after injury. However, over-activation and/or the sustained presence of these signals produce the opposite effect, resulting in secondary cell death, chronic inflammation and scarring. Carefully balancing the inflammatory response is therefore essential and a critical part of successful. We have established that induced inflammation improves neural regeneration and that immune suppression blocks neural regeneration in the zebrafish spinal cord and brain. Furthermore, leukocytes are the source for the pro-regenerative signals and leukocyte resolution overlaps with completed regeneration. We have identified and number of key candidate that orchestrate neural regeneration by acutely initiating the pro-regenerative programmes and later resolving inflammation. The aim of this project is to identify cellular targets and how these pathways interact using in vivo imaging and genetic approaches such as CRISPR/CAS mediated generation of mutant zebrafish.