Document Detail


Hes genes regulate size, shape and histogenesis of the nervous system by control of the timing of neural stem cell differentiation.
MedLine Citation:
PMID:  15496443     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Radial glial cells derive from neuroepithelial cells, and both cell types are identified as neural stem cells. Neural stem cells are known to change their competency over time during development: they initially undergo self-renewal only and then give rise to neurons first and glial cells later. Maintenance of neural stem cells until late stages is thus believed to be essential for generation of cells in correct numbers and diverse types, but little is known about how the timing of cell differentiation is regulated and how its deregulation influences brain organogenesis. Here, we report that inactivation of Hes1 and Hes5, known Notch effectors, and additional inactivation of Hes3 extensively accelerate cell differentiation and cause a wide range of defects in brain formation. In Hes-deficient embryos, initially formed neuroepithelial cells are not properly maintained, and radial glial cells are prematurely differentiated into neurons and depleted without generation of late-born cells. Furthermore, loss of radial glia disrupts the inner and outer barriers of the neural tube, disorganizing the histogenesis. In addition, the forebrain lacks the optic vesicles and the ganglionic eminences. Thus, Hes genes are essential for generation of brain structures of appropriate size, shape and cell arrangement by controlling the timing of cell differentiation. Our data also indicate that embryonic neural stem cells change their characters over time in the following order: Hes-independent neuroepithelial cells, transitory Hes-dependent neuroepithelial cells and Hes-dependent radial glial cells.
Authors:
Jun Hatakeyama; Yasumasa Bessho; Kazuo Katoh; Shigeo Ookawara; Makio Fujioka; François Guillemot; Ryoichiro Kageyama
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-10-20
Journal Detail:
Title:  Development (Cambridge, England)     Volume:  131     ISSN:  0950-1991     ISO Abbreviation:  Development     Publication Date:  2004 Nov 
Date Detail:
Created Date:  2004-10-28     Completed Date:  2005-01-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8701744     Medline TA:  Development     Country:  England    
Other Details:
Languages:  eng     Pagination:  5539-50     Citation Subset:  IM    
Affiliation:
Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Basement Membrane / abnormalities,  embryology,  metabolism
Basic Helix-Loop-Helix Transcription Factors
Cell Differentiation*
DNA-Binding Proteins / deficiency,  genetics,  metabolism*
Eye Abnormalities / embryology,  genetics,  metabolism
Gene Expression Regulation, Developmental
Homeodomain Proteins / genetics,  metabolism*
In Situ Hybridization
Mice
Mice, Knockout
Microscopy, Electron, Scanning
Mutation / genetics
Nerve Tissue Proteins / deficiency,  genetics,  metabolism*
Nervous System / cytology,  embryology*,  metabolism
Neuroglia / cytology,  metabolism,  pathology
Repressor Proteins / genetics,  metabolism*
Spinal Cord / abnormalities,  cytology,  embryology,  metabolism
Stem Cells / cytology*,  metabolism*
Time Factors
Chemical
Reg. No./Substance:
0/Basic Helix-Loop-Helix Transcription Factors; 0/DNA-Binding Proteins; 0/Hes1 protein, mouse; 0/Hes3 protein, mouse; 0/Hes5 protein, mouse; 0/Homeodomain Proteins; 0/Nerve Tissue Proteins; 0/Repressor Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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