Document Detail


p57(KIP2) regulates radial glia and intermediate precursor cell cycle dynamics and lower layer neurogenesis in developing cerebral cortex.
MedLine Citation:
PMID:  22223678     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
During cerebral cortex development, precise control of precursor cell cycle length and cell cycle exit is required for balanced precursor pool expansion and layer-specific neurogenesis. Here, we defined the roles of cyclin-dependent kinase inhibitor (CKI) p57(KIP2), an important regulator of G1 phase, using deletion mutant mice. Mutant mice displayed macroencephaly associated with cortical hyperplasia during late embryogenesis and postnatal development. Embryonically, proliferation of radial glial cells (RGC) and intermediate precursors (IPC) was increased, expanding both populations, with greater effect on IPCs. Furthermore, cell cycle re-entry was increased during early corticogenesis, whereas cell cycle exit was augmented at middle stage. Consequently, neurogenesis was reduced early, whereas it was enhanced during later development. In agreement, the timetable of early neurogenesis, indicated by birthdating analysis, was delayed. Cell cycle dynamics analyses in mutants indicated that p57(KIP2) regulates cell cycle length in both RGCs and IPCs. By contrast, related CKI p27(KIP1) controlled IPC proliferation exclusively. Furthermore, p57(KIP2) deficiency markedly increased RGC and IPC divisions at E14.5, whereas p27(KIP1) increased IPC proliferation at E16.5. Consequently, loss of p57(KIP2) increased primarily layer 5-6 neuron production, whereas loss of p27(KIP1) increased neurons specifically in layers 2-5. In conclusion, our observations suggest that p57(KIP2) and p27(KIP1) control neuronal output for distinct cortical layers by regulating different stages of precursor proliferation, and support a model in which IPCs contribute to both lower and upper layer neuron generation.
Authors:
Georges Mairet-Coello; Anna Tury; Elise Van Buskirk; Kelsey Robinson; Matthieu Genestine; Emanuel DiCicco-Bloom
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Development (Cambridge, England)     Volume:  139     ISSN:  1477-9129     ISO Abbreviation:  Development     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-01-06     Completed Date:  2012-03-06     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  8701744     Medline TA:  Development     Country:  England    
Other Details:
Languages:  eng     Pagination:  475-87     Citation Subset:  IM    
Affiliation:
Department of Neuroscience and Cell Biology, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ 08554, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Brain / abnormalities,  growth & development
Cell Cycle*
Cell Proliferation
Cerebral Cortex / growth & development*
Cyclin-Dependent Kinase Inhibitor p57 / genetics,  metabolism*
Female
Mice
Neurogenesis*
Neuroglia / metabolism*
Sequence Deletion
Stem Cells / metabolism*
Grant Support
ID/Acronym/Agency:
NS32401/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Cdkn1c protein, mouse; 0/Cyclin-Dependent Kinase Inhibitor p57
Comments/Corrections

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