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Downregulation of splicing regulator RBFOX1 compromises visual depth perception
Rbfox1 is a splicing regulator that has been associated with various neurological conditions such as autism spectrum disorder, mental retardation, epilepsy, attention-deficit/hyperactivity disorder and schizophrenia. We show that in adult rodent retinas, Rbfox1 is expressed in all types of retinal g...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6042722/ https://www.ncbi.nlm.nih.gov/pubmed/30001398 http://dx.doi.org/10.1371/journal.pone.0200417 |
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author | Gu, Lei Bok, Dean Yu, Fei Caprioli, Joseph Piri, Natik |
author_facet | Gu, Lei Bok, Dean Yu, Fei Caprioli, Joseph Piri, Natik |
author_sort | Gu, Lei |
collection | PubMed |
description | Rbfox1 is a splicing regulator that has been associated with various neurological conditions such as autism spectrum disorder, mental retardation, epilepsy, attention-deficit/hyperactivity disorder and schizophrenia. We show that in adult rodent retinas, Rbfox1 is expressed in all types of retinal ganglion cells (RGCs) and in certain subsets of amacrine cells (ACs), within the inner nuclear (INL) and ganglion cell (GCL) layers. In the INL, all Rbfox1-positive cells were colocalized with GABAergic ACs, however not all GABAergic ACs were immunostained for Rbfox1. In the GCL, a vast majority of GABAergic dACs were Rbfox1-immunopositive. Furthermore, all cholinergic starburst ACs (SACs) in the INL (type a) and in the GCL (type b) were Rbfox1 positive. The expression of Rbfox1 in the retina significantly overlapped with expression of Rbfox2, another member of Rbfox family of proteins. Rbfox2, in addition to RGCs and ACs, was also expressed in horizontal cells. In developing retinas at E12 and E15, Rbfox1 is localized to the cytoplasm of differentiating RGCs and ACs. Between P0 and P5, Rbfox1 subcellular localization switched from cytoplasmic to predominantly nuclear. Downregulation of Rbfox1 in adult Rbfox1(loxP/loxP) mice had no detectable effect on retinal gross morphology. However, the visual cliff test revealed marked abnormalities of depth perception of these animals. RNA sequencing of retinal transcriptomes of control and Rbfox1 knockout animals identified a number of Rbfox1-regulated genes that are involved in establishing neuronal circuits and synaptic transmission, including Vamp1, Vamp2, Snap25, Trak2, and Slc1A7, suggesting the role of Rbfox1 in facilitating synaptic communications between ACs and RGCs. |
format | Online Article Text |
id | pubmed-6042722 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-60427222018-07-19 Downregulation of splicing regulator RBFOX1 compromises visual depth perception Gu, Lei Bok, Dean Yu, Fei Caprioli, Joseph Piri, Natik PLoS One Research Article Rbfox1 is a splicing regulator that has been associated with various neurological conditions such as autism spectrum disorder, mental retardation, epilepsy, attention-deficit/hyperactivity disorder and schizophrenia. We show that in adult rodent retinas, Rbfox1 is expressed in all types of retinal ganglion cells (RGCs) and in certain subsets of amacrine cells (ACs), within the inner nuclear (INL) and ganglion cell (GCL) layers. In the INL, all Rbfox1-positive cells were colocalized with GABAergic ACs, however not all GABAergic ACs were immunostained for Rbfox1. In the GCL, a vast majority of GABAergic dACs were Rbfox1-immunopositive. Furthermore, all cholinergic starburst ACs (SACs) in the INL (type a) and in the GCL (type b) were Rbfox1 positive. The expression of Rbfox1 in the retina significantly overlapped with expression of Rbfox2, another member of Rbfox family of proteins. Rbfox2, in addition to RGCs and ACs, was also expressed in horizontal cells. In developing retinas at E12 and E15, Rbfox1 is localized to the cytoplasm of differentiating RGCs and ACs. Between P0 and P5, Rbfox1 subcellular localization switched from cytoplasmic to predominantly nuclear. Downregulation of Rbfox1 in adult Rbfox1(loxP/loxP) mice had no detectable effect on retinal gross morphology. However, the visual cliff test revealed marked abnormalities of depth perception of these animals. RNA sequencing of retinal transcriptomes of control and Rbfox1 knockout animals identified a number of Rbfox1-regulated genes that are involved in establishing neuronal circuits and synaptic transmission, including Vamp1, Vamp2, Snap25, Trak2, and Slc1A7, suggesting the role of Rbfox1 in facilitating synaptic communications between ACs and RGCs. Public Library of Science 2018-07-12 /pmc/articles/PMC6042722/ /pubmed/30001398 http://dx.doi.org/10.1371/journal.pone.0200417 Text en © 2018 Gu 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Gu, Lei Bok, Dean Yu, Fei Caprioli, Joseph Piri, Natik Downregulation of splicing regulator RBFOX1 compromises visual depth perception |
title | Downregulation of splicing regulator RBFOX1 compromises visual depth perception |
title_full | Downregulation of splicing regulator RBFOX1 compromises visual depth perception |
title_fullStr | Downregulation of splicing regulator RBFOX1 compromises visual depth perception |
title_full_unstemmed | Downregulation of splicing regulator RBFOX1 compromises visual depth perception |
title_short | Downregulation of splicing regulator RBFOX1 compromises visual depth perception |
title_sort | downregulation of splicing regulator rbfox1 compromises visual depth perception |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6042722/ https://www.ncbi.nlm.nih.gov/pubmed/30001398 http://dx.doi.org/10.1371/journal.pone.0200417 |
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