Regulation and function of HDAC1 in spinal neuron regeneration in zebrafish

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After spinal cord injury, nerve cells in the vicinity of the injury site are destroyed and not replaced. In contrast, in zebrafish, which are capable of full spinal cord regeneration, nerve cells are replaced. The source for new nerve cells are special progenitor cells. These progenitor cells also exist in the spinal cord of mammals, but fail to generate new neurons. We want to understand how progenitor cells in zebrafish can flexibly switch on the production of nerve cells after injury. In preliminary experiments we have identified a DNA-modifying enzyme, called HDAC1, as important. We will manipulate the activity of this enzyme after spinal cord injury in zebrafish using specific drugs and transgenic fish to determine whether HDAC1 is necessary for progenitor cell activity. We will determine how HDAC1 is activated by inflammatory events at the injury site. Then we will identify alterations in gene activity mediated by HDAC1. This will give us important insights into regeneration of new neurons in a vertebrate system. Understanding the important factors in the spinal progenitor cells that allow for neurogenesis in zebrafish may lead to new targets for future therapeutic aiming to harness the endogenous repair capacity of spinal progenitor cells in mammals.