Cerebellar granule cell replenishment postinjury by adaptive reprogramming of Nestin(+) progenitors Journal Article

   

Authors:	Wojcinski, A.; Lawton, A. K.; Bayin, N. S.; Lao, Z.; Stephen, D. N.; Joyner, A. L.
Article Title:	Cerebellar granule cell replenishment postinjury by adaptive reprogramming of Nestin(+) progenitors
Abstract:	Regeneration of several organs involves adaptive reprogramming of progenitors, but the intrinsic capacity of the developing brain to replenish lost cells remains largely unknown. Here we found that the developing cerebellum has unappreciated progenitor plasticity, since it undergoes near full growth and functional recovery following acute depletion of granule cells, the most plentiful neuron population in the brain. We demonstrate that following postnatal ablation of granule cell progenitors, Nestin-expressing progenitors, specified during mid-embryogenesis to produce astroglia and interneurons, switch their fate and generate granule neurons in mice. Moreover, Hedgehog signaling in two Nestin-expressing progenitor populations is crucial not only for the compensatory replenishment of granule neurons but also for scaling interneuron and astrocyte numbers. Thus, we provide insights into the mechanisms underlying robustness of circuit formation in the cerebellum and speculate that adaptive reprogramming of progenitors in other brain regions plays a greater role than appreciated in developmental regeneration. © 2017 Nature America, Inc., part of Springer Nature. All rights reserved.
Keywords:	adult; controlled study; protein expression; nonhuman; protein function; cell proliferation; animal cell; mouse; animal; metabolism; animals; mice; animal tissue; cerebellum; sonic hedgehog protein; animal experiment; astrocyte; hedgehog proteins; embryo development; neural stem cell; cell differentiation; neurons; in vitro study; radiation response; physiology; genetic manipulation; transgenic mouse; mice, transgenic; interneuron; interneurons; newborn; cell migration; animals, newborn; neural stem cells; nestin; nervous system development; neurogenesis; nerve cell; nuclear reprogramming; astrocytes; limit of quantitation; male; female; priority journal; article; hedgehog signaling; cerebellum granular layer
Journal Title:	Nature Neuroscience
Volume:	20
Issue:	10
ISSN:	1097-6256
Publisher:	Nature Publishing Group
Date Published:	2017-10-01
Start Page:	1361
End Page:	1370
Language:	English
DOI:	10.1038/nn.4621
PUBMED:	28805814
PROVIDER:	scopus
PMCID:	PMC5614835
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85029945778&doi=10.1038%2fnn.4621&partnerID=40&md5=d8f1c131ab6537bdcc03ff4c62b73fcf
Notes:	Article -- Export Date: 2 November 2017 -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/116626