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Onecut1 and Onecut2 Play Critical Roles in the Development of the Mouse Retina

The entire repertoire of intrinsic factors that control the cell fate determination process of specific retinal neurons has yet to be fully identified. Single cell transcriptome profiling experiments of retinal progenitor cells revealed considerable gene expression heterogeneity between individual c...

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Autores principales: Goetz, Jillian J., Martin, Gregory M., Chowdhury, Rebecca, Trimarchi, Jeffrey M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4196951/
https://www.ncbi.nlm.nih.gov/pubmed/25313862
http://dx.doi.org/10.1371/journal.pone.0110194
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author Goetz, Jillian J.
Martin, Gregory M.
Chowdhury, Rebecca
Trimarchi, Jeffrey M.
author_facet Goetz, Jillian J.
Martin, Gregory M.
Chowdhury, Rebecca
Trimarchi, Jeffrey M.
author_sort Goetz, Jillian J.
collection PubMed
description The entire repertoire of intrinsic factors that control the cell fate determination process of specific retinal neurons has yet to be fully identified. Single cell transcriptome profiling experiments of retinal progenitor cells revealed considerable gene expression heterogeneity between individual cells, especially among different classes of transcription factors. In this study, we show that two of those factors, Onecut1 and Onecut2, are expressed during mouse retinal development. Using mice that are deficient for each of these transcription factors, we further demonstrate a significant loss (∼70–80%) of horizontal cells in the absence of either of these proteins, while the other retinal cells appear at normal numbers. Microarray profiling experiments performed on knockout retinas revealed defects in horizontal cell genes as early as E14.5. Additional profiling assays showed an upregulation of several stress response genes in the adult Onecut2 knockout, suggesting that the integrity of the retina is compromised in the absence of normal numbers of horizontal cells. Interestingly, melanopsin, the gene coding for the photopigment found in photosensitive ganglion cells, was observed to be upregulated in Onecut1 deficient retinas, pointing to a possible regulatory role for Onecut1. Taken together, our data show that similar to Onecut1, Onecut2 is also necessary for the formation of normal numbers of horizontal cells in the developing retina.
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spelling pubmed-41969512014-10-16 Onecut1 and Onecut2 Play Critical Roles in the Development of the Mouse Retina Goetz, Jillian J. Martin, Gregory M. Chowdhury, Rebecca Trimarchi, Jeffrey M. PLoS One Research Article The entire repertoire of intrinsic factors that control the cell fate determination process of specific retinal neurons has yet to be fully identified. Single cell transcriptome profiling experiments of retinal progenitor cells revealed considerable gene expression heterogeneity between individual cells, especially among different classes of transcription factors. In this study, we show that two of those factors, Onecut1 and Onecut2, are expressed during mouse retinal development. Using mice that are deficient for each of these transcription factors, we further demonstrate a significant loss (∼70–80%) of horizontal cells in the absence of either of these proteins, while the other retinal cells appear at normal numbers. Microarray profiling experiments performed on knockout retinas revealed defects in horizontal cell genes as early as E14.5. Additional profiling assays showed an upregulation of several stress response genes in the adult Onecut2 knockout, suggesting that the integrity of the retina is compromised in the absence of normal numbers of horizontal cells. Interestingly, melanopsin, the gene coding for the photopigment found in photosensitive ganglion cells, was observed to be upregulated in Onecut1 deficient retinas, pointing to a possible regulatory role for Onecut1. Taken together, our data show that similar to Onecut1, Onecut2 is also necessary for the formation of normal numbers of horizontal cells in the developing retina. Public Library of Science 2014-10-14 /pmc/articles/PMC4196951/ /pubmed/25313862 http://dx.doi.org/10.1371/journal.pone.0110194 Text en © 2014 Goetz et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Goetz, Jillian J.
Martin, Gregory M.
Chowdhury, Rebecca
Trimarchi, Jeffrey M.
Onecut1 and Onecut2 Play Critical Roles in the Development of the Mouse Retina
title Onecut1 and Onecut2 Play Critical Roles in the Development of the Mouse Retina
title_full Onecut1 and Onecut2 Play Critical Roles in the Development of the Mouse Retina
title_fullStr Onecut1 and Onecut2 Play Critical Roles in the Development of the Mouse Retina
title_full_unstemmed Onecut1 and Onecut2 Play Critical Roles in the Development of the Mouse Retina
title_short Onecut1 and Onecut2 Play Critical Roles in the Development of the Mouse Retina
title_sort onecut1 and onecut2 play critical roles in the development of the mouse retina
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4196951/
https://www.ncbi.nlm.nih.gov/pubmed/25313862
http://dx.doi.org/10.1371/journal.pone.0110194
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