Investigating regeneration and functional integration of CNS neurons: Lessons from zebrafish genetics and other fish species |
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Authors: | Valerie C Fleisch Brittany FraserW Ted Allison |
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Institution: | a Centre for Prions & Protein Folding Disease, University of Alberta, Edmonton, Alberta, T6G 2M8, Canadab Department of Biological Sciences, University of Alberta, Edmonton, Alberta, T6G 2J9, Canadac Department of Medical Genetics, University of Alberta, Edmonton, Alberta, T6G 2H7, Canada |
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Abstract: | Zebrafish possess a robust, innate CNS regenerative ability. Combined with their genetic tractability and vertebrate CNS architecture, this ability makes zebrafish an attractive model to gain requisite knowledge for clinical CNS regeneration. In treatment of neurological disorders, one can envisage replacing lost neurons through stem cell therapy or through activation of latent stem cells in the CNS. Here we review the evidence that radial glia are a major source of CNS stem cells in zebrafish and thus activation of radial glia is an attractive therapeutic target. We discuss the regenerative potential and the molecular mechanisms thereof, in the zebrafish spinal cord, retina, optic nerve and higher brain centres. We evaluate various cell ablation paradigms developed to induce regeneration, with particular emphasis on the need for (high throughput) indicators that neuronal regeneration has restored sensory or motor function. We also examine the potential confound that regeneration imposes as the community develops zebrafish models of neurodegeneration. We conclude that zebrafish combine several characters that make them a potent resource for testing hypotheses and discovering therapeutic targets in functional CNS regeneration. This article is part of a Special Issue entitled Zebrafish Models of Neurological Diseases. |
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Keywords: | Zebrafish Regeneration Retina Optic nerve Spinal cord Brain Central nervous system Stem cell Glia |
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