Document Detail

Combinatorial regulation of optic cup progenitor cell fate by SOX2 and PAX6.
MedLine Citation:
PMID:  21205789     Owner:  NLM     Status:  MEDLINE    
In humans, haploinsufficiency of either SOX2 or PAX6 is associated with microphthalmia, anophthalmia or aniridia. In this study, through the genetic spatiotemporal specific ablation of SOX2 on both wild-type and Pax6-haploinsufficent backgrounds in the mouse, we have uncovered a transcriptionally distinct and developmentally transient stage of eye development. We show that genetic ablation of SOX2 in the optic cup results in complete loss of neural competence and eventual cell fate conversion to non-neurogenic ciliary epithelium. This cell fate conversion is associated with a striking increase in PAX6, and genetically ablating SOX2 on a Pax6-haploinsufficient background partially rescues the Sox2-mutant phenotype. Collectively, these results demonstrate that precise regulation of the ratio of SOX2 to PAX6 is necessary to ensure accurate progenitor cell specification, and place SOX2 as a decisive factor of neural competence in the retina.
Danielle Matsushima; Whitney Heavner; Larysa H Pevny
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Development (Cambridge, England)     Volume:  138     ISSN:  1477-9129     ISO Abbreviation:  Development     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-05     Completed Date:  2011-01-31     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  8701744     Medline TA:  Development     Country:  England    
Other Details:
Languages:  eng     Pagination:  443-54     Citation Subset:  IM    
UNC Neuroscience Center, University of North Carolina at Chapel Hill, NC 27599, USA.
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MeSH Terms
Cell Differentiation / genetics,  physiology
Ciliary Body / cytology*
Eye Proteins / genetics,  metabolism*
Homeodomain Proteins / genetics,  metabolism*
In Situ Hybridization
Mice, Mutant Strains
Neurons / cytology,  metabolism
Paired Box Transcription Factors / genetics,  metabolism*
Repressor Proteins / genetics,  metabolism*
Retina / cytology,  metabolism
SOXB1 Transcription Factors / genetics,  metabolism*
Stem Cells / cytology*,  metabolism*
Grant Support
5P30NS045892/NS/NINDS NIH HHS; P30-S045892-02//PHS HHS; R01EY018261/EY/NEI NIH HHS; R01MH071822/MH/NIMH NIH HHS
Reg. No./Substance:
0/Eye Proteins; 0/Homeodomain Proteins; 0/PAX6 protein; 0/Paired Box Transcription Factors; 0/Repressor Proteins; 0/SOXB1 Transcription Factors; 0/Sox2 protein, mouse

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

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