Document Detail


Identification of a retina-specific Otx2 enhancer element active in immature developing photoreceptors.
MedLine Citation:
PMID:  21963459     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The homeodomain protein, Otx2, is a critical regulator of vertebrate photoreceptor genesis. However, the genetic elements that define the expression of Otx2 during photoreceptor development are unknown. Therefore, we sought to identify an Otx2 enhancer element that functions in photoreceptor development in order to better understand this specification event. Using the technique of electroporation, we tested a number of evolutionarily conserved elements (ECRs) for expression in the developing retina, and identified ECR2 as having robust activity in the retina. We have characterized this element using a number of assays, including Cre-fate mapping experiments. We found that ECR2 recapitulates expression/function of Otx2 primarily in newly postmitotic photoreceptor cells (PRs), as well as in a subset of retinal progenitor cells (RPCs). ECR2 was also found to be expressed in a subset of horizontal cells (HCs), in keeping with the role of Otx2 in HC development. Furthermore, we determined that the ECR2 element is not active in other Otx2-positive cells such as retinal bipolar cells (BPs), retinal pigmented epithelium (RPE), or the tectum, suggesting that the transcriptional networks controlling Otx2 expression in these cells are unique from those of developing PRs and HCs. These results reveal a distinct molecular state in dividing retinal cells and their newly postmitotic progeny, and provide genetic access to an early and critical transcriptional node involved in the genesis of vertebrate PRs.
Authors:
Mark M Emerson; Constance L Cepko
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-09-21
Journal Detail:
Title:  Developmental biology     Volume:  360     ISSN:  1095-564X     ISO Abbreviation:  Dev. Biol.     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-11-14     Completed Date:  2012-01-05     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  0372762     Medline TA:  Dev Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  241-55     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
Affiliation:
Department of Genetics, Department of Ophthamology, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA. mark_emerson@hms.harvard.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Genetically Modified
Base Sequence
Chick Embryo
Conserved Sequence
DNA / genetics
Enhancer Elements, Genetic*
Evolution, Molecular
Gene Expression Regulation, Developmental
Mice
Mice, Transgenic
Molecular Sequence Data
Otx Transcription Factors / genetics*
Photoreceptor Cells, Vertebrate / cytology,  metabolism*
Phylogeny
Retina / cytology,  enzymology*,  metabolism*
Sequence Homology, Nucleic Acid
Grant Support
ID/Acronym/Agency:
F32 EY018287/EY/NEI NIH HHS; R01 EY009676/EY/NEI NIH HHS; R01 EY009676-16/EY/NEI NIH HHS; R01 EY009676-17/EY/NEI NIH HHS; R01 EY009676-18/EY/NEI NIH HHS; //Howard Hughes Medical Institute
Chemical
Reg. No./Substance:
0/Otx Transcription Factors; 0/Otx2 protein, mouse; 9007-49-2/DNA
Comments/Corrections

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