Semaphorin/plexin interactions in regenerative neurogenesis in zebrafish

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After spinal cord injury, nerve cells are lost and never replaced. Attempts to replace the lost nerve cells are met with limited success in mammalian models. Alternatively, dormant stem cells, which do exist in mammals, could be reactivated to produce new nerve cells, but these cells do not receive the right signal in the injured spinal cord. In contrast, zebrafish stem cells are reactivated after injury and produce nerve cells that are integrated in the injured spinal cord, and fish fully recover from paralysis. As any injury, spinal cord injury elicits an inflammatory reaction, and we have previously shown that this is necessary for regeneration of nerve cells in the zebrafish. However, the identity of the molecular signals that are received by the stem cells in the injured nervous system are unclear. We have analysed the genes that are expressed in single immune cells and stem cells and found specific matching signal (semaporins) and receptor genes (plexins) to be present. Here, we want to test whether this signal/receptor interaction is crucial for regeneration of nerve cells in zebrafish, by mutating the genes in turn and determine whether regeneration is impaired. This research can thus identify the 'language' in which immune cells communicate with spinal stem cells to bring about regeneration. Ultimately, similar signals may be used in therapeutic approaches to instruct the stem cells in mammals to produce nerve cells after an injury and thus bring about repair.