Homeostatic and regenerative neurogenesis in salamanders

Large-scale regeneration in the adult central nervous system is a unique capacity of salamanders among tetrapods. Salamanders can replace neuronal populations, repair damaged nerve fibers and restore tissue architecture in retina, brain and spinal cord, leading to functional recovery. The underlying mechanisms have long been difficult to study due to the paucity of available genomic tools. Recent technological progress, such as genome sequencing, transgenesis and genome editing provide new momentum for systematic interrogation of regenerative processes in the salamander central nervous system. Understanding central nervous system regeneration also entails designing the appropriate molecular, cellular, and behavioral assays. Here we outline the organization of salamander brain structures. With special focus on ependymoglial cells, we integrate cellular and molecular processes of neurogenesis during developmental and adult homeostasis as well as in various injury models. Wherever possible, we correlate developmental and regenerative neurogenesis to the acquisition and recovery of behaviors. Throughout the review we place the findings into an evolutionary context for inter-species comparisons.