Mechanisms of Mitral Cell Regeneration in Zebrafish

ABSTRACT The human brain cannot efficiently regenerate neural tissue after injury or stroke. By contrast, zebrafish possess a striking ability to regenerate injured adult brain tissue from resident neural stem cell populations. The cellular dynamics controlling this phenomenon are unclear and understudied. In this proposal, we will employ a new precision injury tool we developed to dissect the cellular dynamics and mechanistic properties that underly brain regeneration. With this tool, we will genetically induce targeted ablation of specialized neurons called mitral cells in the adult zebrafish olfactory bulb. In preliminary studies, we used this tool to show that after precise ablation, mitral cells of the olfactory bulb regenerate cell bodies and long axons that project to deeper brain centers. Moreover, single-cell transcriptomic analysis during the regeneration time window indicates extensive and dynamic robustness events of the olfactory bulb during mitral cell regeneration. We propose to: 1) interrogate the robustness and neuronal plasticity of the olfactory bulb during regeneration of a precision injury model; and 2) define the molecular basis for mitral cell regeneration in zebrafish. Our work will provide a new view of regenerative capacity in the context of brain injury and a better understanding of the events that surround regeneration of specialized neurons.