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

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 regenera...

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Autores principales: Bayin, N Sumru, Wojcinski, Alexandre, Mourton, Aurelien, Saito, Hiromitsu, Suzuki, Noboru, Joyner, Alexandra L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115187/
https://www.ncbi.nlm.nih.gov/pubmed/30091706
http://dx.doi.org/10.7554/eLife.39879
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author Bayin, N Sumru
Wojcinski, Alexandre
Mourton, Aurelien
Saito, Hiromitsu
Suzuki, Noboru
Joyner, Alexandra L
author_facet Bayin, N Sumru
Wojcinski, Alexandre
Mourton, Aurelien
Saito, Hiromitsu
Suzuki, Noboru
Joyner, Alexandra L
author_sort Bayin, N Sumru
collection PubMed
description 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.
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spelling pubmed-61151872018-09-04 Age-dependent dormant resident progenitors are stimulated by injury to regenerate Purkinje neurons Bayin, N Sumru Wojcinski, Alexandre Mourton, Aurelien Saito, Hiromitsu Suzuki, Noboru Joyner, Alexandra L eLife Developmental Biology 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. eLife Sciences Publications, Ltd 2018-08-09 /pmc/articles/PMC6115187/ /pubmed/30091706 http://dx.doi.org/10.7554/eLife.39879 Text en © 2018, Bayin et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Developmental Biology
Bayin, N Sumru
Wojcinski, Alexandre
Mourton, Aurelien
Saito, Hiromitsu
Suzuki, Noboru
Joyner, Alexandra L
Age-dependent dormant resident progenitors are stimulated by injury to regenerate Purkinje neurons
title Age-dependent dormant resident progenitors are stimulated by injury to regenerate Purkinje neurons
title_full Age-dependent dormant resident progenitors are stimulated by injury to regenerate Purkinje neurons
title_fullStr Age-dependent dormant resident progenitors are stimulated by injury to regenerate Purkinje neurons
title_full_unstemmed Age-dependent dormant resident progenitors are stimulated by injury to regenerate Purkinje neurons
title_short Age-dependent dormant resident progenitors are stimulated by injury to regenerate Purkinje neurons
title_sort age-dependent dormant resident progenitors are stimulated by injury to regenerate purkinje neurons
topic Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115187/
https://www.ncbi.nlm.nih.gov/pubmed/30091706
http://dx.doi.org/10.7554/eLife.39879
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