Zebrafish as a Model System for Successful Spinal Cord Regeneration

Abstract

OverviewAdult zebrafish, in contrast to mammals, are capable of functional regeneration after spinal cord injury. Regeneration studies in zebrafish benefit from the model status of this vertebrate for research on developmental biology. This model status has helped to make available molecular tools such as genetic manipulation, expression profiling and gene knock-down techniques. Behavioral recovery after spinal injury is clearly quantifiable in zebrafish using different tests. The anatomical basis for behavioral recovery is supported by a surprising heterogeneity in axon regrowth and gene expression in different neuronal populations. In addition, specific gene regulation in non-axotomized spinal neurons indicates plasticity of the spinal circuitry after injury, which may also contribute to behavioral recovery. Gaps in our understanding of the spinal network are being filled by several studies of the more simple spinal network found in larval zebrafish. Gene knock-down, interference with intracellular messenger systems and promoter analysis in neurons after lesion are all possible in vivo, demonstrating the experimental accessibility of the system. At the same time, environmental inhibitors of axon re-growth appear not to be prominent in fish. Thus, environmental conditions may not confound the study of neuronal reactions to axotomy. Zebrafish, therefore, offer the opportunity to perform in-vivo studies of the mechanisms that lead to successful recovery after spinal cord injury, from the molecular to the systems levels.

Different Mechanisms Regulate Expression of Zebrafish Myelin Protein Zero (P0) in Myelinating Oligodendrocytes and Its Induction following Axonal Injury

“…In addition to cell-autonomous events in zebrafish neurons that favor axonal regeneration, the extracellular environment of the zebrafish CNS is thought to provide a permissive setting for axon growth and guidance cues for anatomical restoration of fiber tracts. Unlike mammals, glial scar-derived growth-inhibitory chondroitin sulfates (5) and secreted axon-repellant semaphorins (6) were not increased in the injured zebrafish optic nerve. Furthermore, unlike mammalian CNS myelin, fish myelin and oligodendrocytes did not markedly inhibit axon growth (7); the zebrafish orthologue of the mammalian oligodendrocyte-derived axon growth inhibitor Nogo-A was found to lack a key inhibitory domain (8), which may partially account for these observations.…”

“…The expression of growth-promoting cell surface proteins in zebrafish oligodendrocytes following CNS injury is thought to stimulate axonal regeneration (6). Myelin protein zero (P0), 4 expressed in Schwann cells in mammals, shows axonal growthpromoting properties in vitro (9), and the mpz gene encoding the zebrafish P0 orthologue is strongly up-regulated in oligodendrocytes in regenerating white matter tracts following CNS axonal injury (10).…”

Function of Sox2 in ependymal cells of lesioned spinal cords in adult zebrafish

“…In contrast to such tragic events, adult zebrafish can regenerate motor neurons in the spinal cord and protect upper motor neurons in the brainstem against cell death via several regenerative mechanisms (Becker and Becker, 2007;Dias et al, 2012;Ogai et al, 2012).…”

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“…Numerous experimental studies of rodent models appear to be costly affairs for screening of thousands of novel, potential candidate small molecules. Recently, Zebrafish (Danio rerio) have emerged as a promising novel organism to study neuroscience 10 and other related areas. This species has relatively 84 percent genetic homology to humans 11 and provides many advantages when compared to other vertebrates such as low cost, easy handling and faster reproduction 12 .…”