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Fishes and salamanders regenerate neurons, but mammals only generate glial cells after spinal injury.The spinal ependymal zones in fish and mammals contain progenitor cells with neurogenic potential.Progenitor cells in the spinal cords of fish and mammals share a number of morphological features and molecular signatures.Comparisons of cells in the spinal ependymal zone of fish and mammals may identify regenerative programmes.Spinal cord injury results in the loss of neurons and axonal connections. In mammals, including humans, this loss is permanent, but is repaired in other vertebrates, such as salamanders and fishes. Cells in the ependymal niche play a pivotal role for the outcome after injury. These cells initiate proliferation and generate new neurons of different types in regenerating species, but only glial cells, contributing to the glial scar, in mammals. Here we compare the cellular and molecular properties of ependymal zone cells and their environment across vertebrate classes. We point out communalities and differences between vertebrates capable of neuronal regeneration and those that are not. Comparisons like these may ultimately lead to the identification of factors that tip the balance for ependymal zone cells in mammals to produce appropriate neural cells for endogenous repair after spinal cord injury.