Potency and contribution of zebrafish progenitors during innate spinal cord repair

ABSTRACT Around 18,000 Americans suffer new spinal cord injuries (SCI) each year. Primary and secondary damages caused by SCI permanently impair sensory and motor functions, which require long-term therapeutic, rehabilitative, and psychological interventions. Thus, developing therapies to treat or reverse SCI is a pressing need in regenerative medicine. In contrast to mammals, teleost fish naturally regenerate functional neural tissue and reverse paralysis after complete spinal cord (SC) transection. Following SCI, pro-regenerative glial and neuronal responses distinguish the zebrafish SC from the mammalian SC and enable natural repair post-injury. Importantly, these pro-regenerative processes occur without the detrimental outcomes of reactive gliosis or neurotoxicity elicited by the mammalian SC. However, little is known about the cellular and molecular mechanisms that direct glial and neuronal regeneration in zebrafish. In this proposal, we will determine the potency of the progenitor cells that direct SC repair, and the regenerative roles of neurogenic and gliogenic progenitor cell types after SCI. These studies will provide a mechanistic understanding of glial and neuronal regeneration during zebrafish SC repair, and will guide approaches for manipulating SCI outcomes in mammals.