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Genes and signaling networks regulated during zebrafish optic vesicle morphogenesis
BACKGROUND: The genetic cascades underpinning vertebrate early eye morphogenesis are poorly understood. One gene family essential for eye morphogenesis encodes the retinal homeobox (Rx) transcription factors. Mutations in the human retinal homeobox gene (RAX) can lead to gross morphological phenotyp...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4190348/ https://www.ncbi.nlm.nih.gov/pubmed/25266257 http://dx.doi.org/10.1186/1471-2164-15-825 |
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author | Yin, Jun Morrissey, Maria E Shine, Lisa Kennedy, Ciarán Higgins, Desmond G Kennedy, Breandán N |
author_facet | Yin, Jun Morrissey, Maria E Shine, Lisa Kennedy, Ciarán Higgins, Desmond G Kennedy, Breandán N |
author_sort | Yin, Jun |
collection | PubMed |
description | BACKGROUND: The genetic cascades underpinning vertebrate early eye morphogenesis are poorly understood. One gene family essential for eye morphogenesis encodes the retinal homeobox (Rx) transcription factors. Mutations in the human retinal homeobox gene (RAX) can lead to gross morphological phenotypes ranging from microphthalmia to anophthalmia. Zebrafish rx3 null mutants produce a similar striking eyeless phenotype with an associated expanded forebrain. Thus, we used zebrafish rx3(-/-) mutants as a model to uncover an Rx3-regulated gene network during early eye morphogenesis. RESULTS: Rx3-regulated genes were identified using whole transcriptomic sequencing (RNA-seq) of rx3(-/-) mutants and morphologically wild-type siblings during optic vesicle morphogenesis. A gene co-expression network was then constructed for the Rx3-regulated genes, identifying gene cross-talk during early eye development. Genes highly connected in the network are hub genes, which tend to exhibit higher expression changes between rx3(-/-) mutants and normal phenotype siblings. Hub genes down-regulated in rx3(-/-) mutants encompass homeodomain transcription factors and mediators of retinoid-signaling, both associated with eye development and known human eye disorders. In contrast, genes up-regulated in rx3(-/-) mutants are centered on Wnt signaling pathways, associated with brain development and disorders. The temporal expression pattern of Rx3-regulated genes was further profiled during early development from maternal stage until visual function is fully mature. Rx3-regulated genes exhibited synchronized expression patterns, and a transition of gene expression during the early segmentation stage when Rx3 was highly expressed. Furthermore, most of these deregulated genes are enriched with multiple RAX-binding motif sequences on the gene promoter. CONCLUSIONS: Here, we assembled a comprehensive model of Rx3-regulated genes during early eye morphogenesis. Rx3 promotes optic vesicle morphogenesis and represses brain development through a highly correlated and modulated network, exhibiting repression of genes mediating Wnt signaling and concomitant enhanced expression of homeodomain transcription factors and retinoid-signaling genes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-825) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4190348 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-41903482014-10-10 Genes and signaling networks regulated during zebrafish optic vesicle morphogenesis Yin, Jun Morrissey, Maria E Shine, Lisa Kennedy, Ciarán Higgins, Desmond G Kennedy, Breandán N BMC Genomics Research Article BACKGROUND: The genetic cascades underpinning vertebrate early eye morphogenesis are poorly understood. One gene family essential for eye morphogenesis encodes the retinal homeobox (Rx) transcription factors. Mutations in the human retinal homeobox gene (RAX) can lead to gross morphological phenotypes ranging from microphthalmia to anophthalmia. Zebrafish rx3 null mutants produce a similar striking eyeless phenotype with an associated expanded forebrain. Thus, we used zebrafish rx3(-/-) mutants as a model to uncover an Rx3-regulated gene network during early eye morphogenesis. RESULTS: Rx3-regulated genes were identified using whole transcriptomic sequencing (RNA-seq) of rx3(-/-) mutants and morphologically wild-type siblings during optic vesicle morphogenesis. A gene co-expression network was then constructed for the Rx3-regulated genes, identifying gene cross-talk during early eye development. Genes highly connected in the network are hub genes, which tend to exhibit higher expression changes between rx3(-/-) mutants and normal phenotype siblings. Hub genes down-regulated in rx3(-/-) mutants encompass homeodomain transcription factors and mediators of retinoid-signaling, both associated with eye development and known human eye disorders. In contrast, genes up-regulated in rx3(-/-) mutants are centered on Wnt signaling pathways, associated with brain development and disorders. The temporal expression pattern of Rx3-regulated genes was further profiled during early development from maternal stage until visual function is fully mature. Rx3-regulated genes exhibited synchronized expression patterns, and a transition of gene expression during the early segmentation stage when Rx3 was highly expressed. Furthermore, most of these deregulated genes are enriched with multiple RAX-binding motif sequences on the gene promoter. CONCLUSIONS: Here, we assembled a comprehensive model of Rx3-regulated genes during early eye morphogenesis. Rx3 promotes optic vesicle morphogenesis and represses brain development through a highly correlated and modulated network, exhibiting repression of genes mediating Wnt signaling and concomitant enhanced expression of homeodomain transcription factors and retinoid-signaling genes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-825) contains supplementary material, which is available to authorized users. BioMed Central 2014-09-30 /pmc/articles/PMC4190348/ /pubmed/25266257 http://dx.doi.org/10.1186/1471-2164-15-825 Text en © Yin et al.; licensee BioMed Central Ltd. 2014 This article is published under license to BioMed Central Ltd. 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 work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Yin, Jun Morrissey, Maria E Shine, Lisa Kennedy, Ciarán Higgins, Desmond G Kennedy, Breandán N Genes and signaling networks regulated during zebrafish optic vesicle morphogenesis |
title | Genes and signaling networks regulated during zebrafish optic vesicle morphogenesis |
title_full | Genes and signaling networks regulated during zebrafish optic vesicle morphogenesis |
title_fullStr | Genes and signaling networks regulated during zebrafish optic vesicle morphogenesis |
title_full_unstemmed | Genes and signaling networks regulated during zebrafish optic vesicle morphogenesis |
title_short | Genes and signaling networks regulated during zebrafish optic vesicle morphogenesis |
title_sort | genes and signaling networks regulated during zebrafish optic vesicle morphogenesis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4190348/ https://www.ncbi.nlm.nih.gov/pubmed/25266257 http://dx.doi.org/10.1186/1471-2164-15-825 |
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