Document Detail

An inhibition of cyclin-dependent kinases that lengthens, but does not arrest, neuroepithelial cell cycle induces premature neurogenesis.
MedLine Citation:
PMID:  14625388     Owner:  NLM     Status:  MEDLINE    
The G1 phase of the cell cycle of neuroepithelial cells, the progenitors of all neurons of the mammalian central nervous system, has been known to lengthen concomitantly with the onset and progression of neurogenesis. We have investigated whether lengthening of the G1 phase of the neuroepithelial cell cycle is a cause, rather than a consequence, of neurogenesis. As an experimental system, we used whole mouse embryo culture, which was found to exactly reproduce the temporal and spatial gradients of the onset of neurogenesis occurring in utero. Olomoucine, a cell-permeable, highly specific inhibitor of cyclin-dependent kinases and G1 progression, was found to significantly lengthen, but not arrest, the cell cycle of neuroepithelial cells when used at 80 microM. This olomoucine treatment induced, in the telencephalic neuroepithelium of embryonic day 9.5 to 10.5 mouse embryos developing in whole embryo culture to embryonic day 10.5, (i) the premature up-regulation of TIS21, a marker identifying neuroepithelial cells that have switched from proliferative to neuron-generating divisions, and (ii) the premature generation of neurons. Our data indicate that lengthening G1 can alone be sufficient to induce neuroepithelial cell differentiation. We propose a model that links the effects of cell fate determinants and asymmetric cell division to the length of the cell cycle.
Federico Calegari; Wieland B Huttner
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of cell science     Volume:  116     ISSN:  0021-9533     ISO Abbreviation:  J. Cell. Sci.     Publication Date:  2003 Dec 
Date Detail:
Created Date:  2003-11-19     Completed Date:  2004-05-17     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0052457     Medline TA:  J Cell Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  4947-55     Citation Subset:  IM    
Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, D-01307, Dresden, Germany.
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MeSH Terms
Cell Cycle / physiology*
Cyclin-Dependent Kinases / antagonists & inhibitors,  metabolism*
Embryo, Mammalian / cytology,  metabolism*
Enzyme Inhibitors / pharmacology
G1 Phase
Gene Expression Regulation, Developmental
Genes, Tumor Suppressor
Immediate-Early Proteins
Neurons / metabolism*
Purines / pharmacology
Tumor Suppressor Proteins
Reg. No./Substance:
0/Btg2 protein, mouse; 0/Enzyme Inhibitors; 0/Immediate-Early Proteins; 0/Purines; 0/Tumor Suppressor Proteins; 0/olomoucine; 525-79-1/Kinetin; EC Kinases

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