Document Detail


Genetic regulation of proliferation/differentiation characteristics of neural progenitor cells in the developing neocortex.
MedLine Citation:
PMID:  19464833     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Brain size variation among different mammals is tightly associated with different levels of cerebral function. Mechanisms that regulate the number of neurons and hence the size of the brain must be at least partially embedded within the very early phase of neocortical development, that is, embedded in proliferation/differentiation characteristics of the neural progenitor cells (NPCs) of the neocortex. Here we review a sequence of critical events through which the neocortex is formed in the embryonic forebrain, with particular emphasis on cell cycle kinetics of the NPCs that produce non-GABAergic projection neurons, the majority of neurons in the neocortex. In general, the critical parameters that determine the total number of cells produced by a given progenitor population through a sequence of cell cycles are (1) the number of cell cycles that constitute the production period and (2) the probability of cell cycle exit (Q fraction or Q) of progenitor cells for each of the cell cycles. We will also review molecular mechanisms that modulate the critical parameters above, with a special reference to the cell cycle regulatory protein p27(Kip1), inhibitor of G1 phase progression of the cell cycle. Finally the neocortical dysgenesis caused by genetic modification in mice where p27(Kip1) is either deleted or overexpressed is presented as examples of neuron number changes and resultant neocortical dysgenesis by Q fraction alteration.
Authors:
Takayuki Mitsuhashi; Takao Takahashi
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Publication Detail:
Type:  Journal Article; Review     Date:  2009-05-22
Journal Detail:
Title:  Brain & development     Volume:  31     ISSN:  1872-7131     ISO Abbreviation:  Brain Dev.     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-07-06     Completed Date:  2009-09-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7909235     Medline TA:  Brain Dev     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  553-7     Citation Subset:  IM    
Affiliation:
Department of Pediatrics, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Cycle / genetics,  physiology
Cyclin-Dependent Kinase Inhibitor p27 / metabolism
Gene Expression Regulation, Developmental*
Neocortex / embryology*,  growth & development*,  physiology
Neurogenesis / genetics*
Neurons / physiology*
Stem Cells / physiology*
Chemical
Reg. No./Substance:
147604-94-2/Cyclin-Dependent Kinase Inhibitor p27

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