Stem-Cell-Driven Growth and Regrowth of the Adult Spinal Cord in Teleost Fish

The spinal cord of the teleost fish Apteronotus leptorhynchus continues to grow during adulthood, in concert with the overall body growth. Immunohistological studies, combined with mathematical modeling, suggest that this growth is driven by proliferative activity of Sox2-expressing stem/progenitor cells (SPCs) and by cell drift due to population pressure. The SPCs exhibit high volumetric density in the caudal filament and the ependymal layer. Nevertheless, the majority of these cells are found in the parenchyma throughout the rostro-caudal axis of the spinal cord, albeit at much lower volumetric densities than in the ependymal layer. The SPCs give rise, via transit-amplifying cells, to neurons and glia. The relative number of neurons and glia is primarily regulated through apoptosis of supernumerary neurons. Quantitative analysis has demonstrated that the continued cell proliferation results in additive neurogenesis. This addition includes adult-born spinal electromotoneurons, thereby resulting in a continuous increase in the amplitude of the fish's electric organ discharge during adult life. Amputation of the caudal part of the spinal cord induces initially a degenerative response, dominated by massive apoptotic cell death in spinal cord tissue immediately rostral to the injury site, and distinguished by a partial loss of the electric organ discharge amplitude. This phase is followed by a regenerative response, characterized by absence of gliosis and by rapid stem-cell-driven tissue regrowth. Although the quality of the regenerated tissue is variable among individuals, the structural repair has led in every fish examined thus far to full recovery of the electric organ discharge amplitude.