Document Detail


The generation of superficial cortical layers is regulated by levels of the transcription factor Pax6.
MedLine Citation:
PMID:  20413449     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The ventricular zone (VZ) of the embryonic dorsal telencephalon is a major site for generating cortical projection neurons. The transcription factor Pax6 is highly expressed in apical progenitors (APs) residing in the VZ from the earliest stages of corticogenesis. Previous studies mainly focused on Pax6(-/-) mice have implicated Pax6 in regulating cortical progenitor proliferation, neurogenesis, and formation of superficial cortical layers. We analyzed the developing cortex of PAX77 transgenic mice that overexpress Pax6 in its normal domains of expression. We show that Pax6 overexpression increases cell cycle length of APs and drives the system toward neurogenesis. These effects are specific to late stages of corticogenesis, when superficial layer neurons are normally generated, in cortical regions that express Pax6 at the highest levels. The number of superficial layer neurons is reduced in postnatal PAX77 mice, whereas radial migration and lamina specification of cortical neurons are not affected by Pax6 overexpression. Conditional deletion of Pax6 in cortical progenitors at midstages of corticogenesis, by using a tamoxifen-inducible Emx1-CreER line, affected both numbers and specification of late-born neurons in superficial layers of the mutant cortex. Our analyses suggest that correct levels of Pax6 are essential for normal production of superficial layers of the cortex.
Authors:
Petrina A Georgala; Martine Manuel; David J Price
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-04-22
Journal Detail:
Title:  Cerebral cortex (New York, N.Y. : 1991)     Volume:  21     ISSN:  1460-2199     ISO Abbreviation:  Cereb. Cortex     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-12-14     Completed Date:  2011-11-14     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  9110718     Medline TA:  Cereb Cortex     Country:  United States    
Other Details:
Languages:  eng     Pagination:  81-94     Citation Subset:  IM    
Affiliation:
Centre for Integrative Physiology, School of Biomedical Sciences, Genes and Development Group, The University of Edinburgh, Edinburgh, UK. p.georgala@sms.ed.ac.uk
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MeSH Terms
Descriptor/Qualifier:
Animals
Body Patterning* / genetics
Cell Movement / genetics
Cerebral Cortex / embryology*,  growth & development*,  metabolism
Eye Proteins / biosynthesis,  genetics,  physiology*
Female
Gene Expression Regulation, Developmental / physiology
Homeodomain Proteins / biosynthesis,  genetics,  physiology*
Humans
Male
Mice
Mice, Knockout
Mice, Transgenic
Neural Stem Cells / cytology,  metabolism
Neurogenesis* / genetics
Paired Box Transcription Factors / biosynthesis,  genetics,  physiology*
Repressor Proteins / biosynthesis,  genetics,  physiology*
Grant Support
ID/Acronym/Agency:
082456//Howard Hughes Medical Institute; G0800429//Medical Research Council
Chemical
Reg. No./Substance:
0/Eye Proteins; 0/Homeodomain Proteins; 0/PAX6 protein; 0/Paired Box Transcription Factors; 0/Repressor Proteins
Comments/Corrections

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