| Identification of a retina-specific Otx2 enhancer element active in immature developing photoreceptors. | |
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MedLine Citation:
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PMID: 21963459 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Mark M Emerson; Constance L Cepko |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-09-21 |
Journal Detail:
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Title: Developmental biology Volume: 360 ISSN: 1095-564X ISO Abbreviation: Dev. Biol. Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-11-14 Completed Date: 2012-01-05 Revised Date: 2013-02-19 |
Medline Journal Info:
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Nlm Unique ID: 0372762 Medline TA: Dev Biol Country: United States |
Other Details:
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Languages: eng Pagination: 241-55 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Genetics, Department of Ophthamology, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA. mark_emerson@hms.harvard.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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:
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0/Otx Transcription Factors; 0/Otx2 protein, mouse; 9007-49-2/DNA |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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