Age-dependent dormant resident progenitors are stimulated by injury to regenerate Purkinje neurons
- Memorial Sloan Kettering Cancer Center, United States
- Mie University, Japan
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+ neural 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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Alexandra L Joyner
Funding
National Institute of Neurological Disorders and Stroke (R01NS092096)
- Alexandra L Joyner
National Cancer Institute (P30 CA008748-48)
- Alexandra L Joyner
National Institute of Mental Health (R37MH085726)
- Alexandra L Joyner
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All the experiments were performed according to protocols (#07-01-001) approved by the Memorial Sloan Kettering Cancer Center's Institutional Animal Care and Use Committee (IACUC) . Animals were given access to food and water ad libitum and were housed on a 12-hour light/dark cycle.
Copyright
© 2018, Bayin et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Age-dependent dormant resident progenitors are stimulated by injury to regenerate Purkinje neurons
eLife 7:e39879.
https://doi.org/10.7554/eLife.39879
