Age-dependent dormant resident progenitors are stimulated by injury to regenerate Purkinje neurons

Abstract

Outside of the neurogenic niches of the brain, postmitotic neurons have not been found to undergo efficient regeneration. We demonstrate that mouse Purkinje cells (PCs), which are born at midgestation and are crucial for development and function of cerebellar circuits, are rapidly and fully regenerated following their ablation at birth. New PCs are produced from immature FOXP2+ Purkinje cell precursors (iPCs) that are able to enter the cell cycle and support normal cerebellum development. The number of iPCs and their regenerative capacity, however, diminish soon after birth and consequently PCs are poorly replenished when ablated at postnatal day five. Nevertheless, the PC-depleted cerebella reach a normal size by increasing cell size, but scaling of neuron types is disrupted and cerebellar function is impaired. Our findings provide a new paradigm in the field of neuron regeneration by identifying a population of immature neurons that buffers against perinatal brain injury in a stage-dependent process.