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Loss of LMO4 in the Retina Leads to Reduction of GABAergic Amacrine Cells and Functional Deficits
BACKGROUND: LMO4 is a transcription cofactor expressed during retinal development and in amacrine neurons at birth. A previous study in zebrafish reported that morpholino RNA ablation of one of two related genes, LMO4b, increases the size of eyes in embryos. However, the significance of LMO4 in mamm...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2010
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2951357/ https://www.ncbi.nlm.nih.gov/pubmed/20949055 http://dx.doi.org/10.1371/journal.pone.0013232 |
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author | Duquette, Philippe M. Zhou, Xun Yap, Nida Lerma MacLaren, Erik J. Lu, Jesse J. Wallace, Valerie A. Chen, Hsiao-Huei |
author_facet | Duquette, Philippe M. Zhou, Xun Yap, Nida Lerma MacLaren, Erik J. Lu, Jesse J. Wallace, Valerie A. Chen, Hsiao-Huei |
author_sort | Duquette, Philippe M. |
collection | PubMed |
description | BACKGROUND: LMO4 is a transcription cofactor expressed during retinal development and in amacrine neurons at birth. A previous study in zebrafish reported that morpholino RNA ablation of one of two related genes, LMO4b, increases the size of eyes in embryos. However, the significance of LMO4 in mammalian eye development and function remained unknown since LMO4 null mice die prior to birth. METHODOLOGY/PRINCIPAL FINDINGS: We observed the presence of a smaller eye and/or coloboma in ∼40% LMO4 null mouse embryos. To investigate the postnatal role of LMO4 in retinal development and function, LMO4 was conditionally ablated in retinal progenitor cells using the Pax6 alpha-enhancer Cre/LMO4flox mice. We found that these mice have fewer Bhlhb5-positive GABAergic amacrine and OFF-cone bipolar cells. The deficit appears to affect the postnatal wave of Bhlhb5+ neurons, suggesting a temporal requirement for LMO4 in retinal neuron development. In contrast, cholinergic and dopaminergic amacrine, rod bipolar and photoreceptor cell numbers were not affected. The selective reduction in these interneurons was accompanied by a functional deficit revealed by electroretinography, with reduced amplitude of b-waves, indicating deficits in the inner nuclear layer of the retina. CONCLUSIONS/SIGNIFICANCE: Inhibitory GABAergic interneurons play a critical function in controlling retinal image processing, and are important for neural networks in the central nervous system. Our finding of an essential postnatal function of LMO4 in the differentiation of Bhlhb5-expressing inhibitory interneurons in the retina may be a general mechanism whereby LMO4 controls the production of inhibitory interneurons in the nervous system. |
format | Text |
id | pubmed-2951357 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-29513572010-10-14 Loss of LMO4 in the Retina Leads to Reduction of GABAergic Amacrine Cells and Functional Deficits Duquette, Philippe M. Zhou, Xun Yap, Nida Lerma MacLaren, Erik J. Lu, Jesse J. Wallace, Valerie A. Chen, Hsiao-Huei PLoS One Research Article BACKGROUND: LMO4 is a transcription cofactor expressed during retinal development and in amacrine neurons at birth. A previous study in zebrafish reported that morpholino RNA ablation of one of two related genes, LMO4b, increases the size of eyes in embryos. However, the significance of LMO4 in mammalian eye development and function remained unknown since LMO4 null mice die prior to birth. METHODOLOGY/PRINCIPAL FINDINGS: We observed the presence of a smaller eye and/or coloboma in ∼40% LMO4 null mouse embryos. To investigate the postnatal role of LMO4 in retinal development and function, LMO4 was conditionally ablated in retinal progenitor cells using the Pax6 alpha-enhancer Cre/LMO4flox mice. We found that these mice have fewer Bhlhb5-positive GABAergic amacrine and OFF-cone bipolar cells. The deficit appears to affect the postnatal wave of Bhlhb5+ neurons, suggesting a temporal requirement for LMO4 in retinal neuron development. In contrast, cholinergic and dopaminergic amacrine, rod bipolar and photoreceptor cell numbers were not affected. The selective reduction in these interneurons was accompanied by a functional deficit revealed by electroretinography, with reduced amplitude of b-waves, indicating deficits in the inner nuclear layer of the retina. CONCLUSIONS/SIGNIFICANCE: Inhibitory GABAergic interneurons play a critical function in controlling retinal image processing, and are important for neural networks in the central nervous system. Our finding of an essential postnatal function of LMO4 in the differentiation of Bhlhb5-expressing inhibitory interneurons in the retina may be a general mechanism whereby LMO4 controls the production of inhibitory interneurons in the nervous system. Public Library of Science 2010-10-07 /pmc/articles/PMC2951357/ /pubmed/20949055 http://dx.doi.org/10.1371/journal.pone.0013232 Text en Duquette 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 Duquette, Philippe M. Zhou, Xun Yap, Nida Lerma MacLaren, Erik J. Lu, Jesse J. Wallace, Valerie A. Chen, Hsiao-Huei Loss of LMO4 in the Retina Leads to Reduction of GABAergic Amacrine Cells and Functional Deficits |
title | Loss of LMO4 in the Retina Leads to Reduction of GABAergic Amacrine Cells and Functional Deficits |
title_full | Loss of LMO4 in the Retina Leads to Reduction of GABAergic Amacrine Cells and Functional Deficits |
title_fullStr | Loss of LMO4 in the Retina Leads to Reduction of GABAergic Amacrine Cells and Functional Deficits |
title_full_unstemmed | Loss of LMO4 in the Retina Leads to Reduction of GABAergic Amacrine Cells and Functional Deficits |
title_short | Loss of LMO4 in the Retina Leads to Reduction of GABAergic Amacrine Cells and Functional Deficits |
title_sort | loss of lmo4 in the retina leads to reduction of gabaergic amacrine cells and functional deficits |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2951357/ https://www.ncbi.nlm.nih.gov/pubmed/20949055 http://dx.doi.org/10.1371/journal.pone.0013232 |
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