Gene expression profiling of zebrafish embryonic retinal pigment epithelium in vivo
Open accessAbstract
PURPOSE: Eye development and photoreceptor maintenance is dependent on the retinal pigment epithelium (RPE), a thin layer of cells that underlies the neural retina. Despite its importance, development of RPE has not been studied by a genomic approach. In this study, a microarray expression-profiling methodology was established for studying RPE development. METHODS: The intact retina with RPE attached was dissected from developing embryos, and differentially expressed genes in RPE were inferred by comparing the dissected tissues with retinas without RPE, in microarray and statistical analyses. RESULTS: Of the probesets used, 8810 were significantly expressed in RPE at 52 hours postfertilization (hpf), of which 1443 may have biologically meaningful expression levels. Further, 78 and 988 probesets were found to be significantly over- or underexpressed in RPE, respectively, compared with retina. Also, 79.2% (38/48) of the known overexpressed probesets were independently validated as RPE-related transcripts. CONCLUSIONS: The results strongly suggest that this methodology can obtain in vivo RPE-specific gene expression from the zebrafish embryos and identify novel RPE markers.
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Previous descriptions of gene expression in the RPE of zebrafish, chicken, and human have elucidated many of the genes playing roles in RPE biology.
“Previous descriptions of gene expression in the RPE of zebrafish, chicken, and human have elucidated many of the genes playing roles in RPE biology [36]–[38].”
From Gene Expression Analysis of Zebrafish Melanocytes, Iridophores, and Retinal Pigmented Epithelium Reveals Indicators of Biological Function and Developmental Origin (2013) · cites this paper as [36]
The Introduction says the study profiled the developing zebrafish retina, not its retinal pigment epithelium (RPE). The Materials and Methods describe removing the RPE before collecting the retinal tissue. For the zebrafish portion of this multi-citation sentence, the paper therefore describes gene expression in a different tissue. (LLM, conf=0.88)
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Experimental — accuracy not yet measuredMelanocyte and RPE gene expression have been previously characterized.
“Because melanocyte and RPE gene expression have been previously characterized, we do not discuss them in detail here, but present the data as the supplemental tables listed below [36]–[38], [68], [69].”
From Gene Expression Analysis of Zebrafish Melanocytes, Iridophores, and Retinal Pigmented Epithelium Reveals Indicators of Biological Function and Developmental Origin (2013) · cites this paper as [36]
The Materials and Methods describe removing the RPE before profiling retinal RNA, and the Results compare retinal with whole-embryo gene expression. Searches for RPE and melanocyte expression found no passage in our copy characterizing gene expression in either cell type. No page numbers were available for these passages. (LLM, conf=0.75)
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Research works printed but not linked: 26
- [1]Grunwald DJ, Eisen JS. Headwaters of the zebrafish—emergence of a new model vertebrate. Nat Rev Genet. 2002;3:717–724. doi: 10.1038/nrg892. [DOI] [PubMed] [Google Scholar] · DOI
- [2]Rasooly RS, Henken D, Freeman N, Tompkins L, Badman D, Briggs J, et al. Genetic and genomic tools for zebrafish research: the NIH zebrafish initiative. Dev Dyn. 2003;228:490–496. doi: 10.1002/dvdy.10366. [DOI] [PubMed] [Google Scholar] · DOI
- [3]Patton EE, Zon LI. The art and design of genetic screens: zebrafish. Nat Rev Genet. 2001;2:956–966. doi: 10.1038/35103567. [DOI] [PubMed] [Google Scholar] · DOI
- [4]Blackshaw S, Fraioli RE, Furukawa T, Cepko CL. Comprehensive analysis of photoreceptor gene expression and the identification of candidate retinal disease genes. Cell. 2001;107:579–589. doi: 10.1016/s0092-8674(01)00574-8. [DOI] [PubMed] [Google Scholar] · DOI
- [5]Blackshaw S, Harpavat S, Trimarchi J, Cai L, Huang H, Kuo WP, et al. Genomic analysis of mouse retinal development. PLoS Biol. 2004;2:E247. doi: 10.1371/journal.pbio.0020247. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- [6]Sharon D, Blackshaw S, Cepko CL, Dryja TP. Profile of the genes expressed in the human peripheral retina, macula, and retinal pigment epithelium determined through serial analysis of gene expression (SAGE) Proc Natl Acad Sci USA. 2002;99:315–320. doi: 10.1073/pnas.012582799. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- [7]Livesey FJ, Furukawa T, Steffen MA, Church GM, Cepko CL. Microarray analysis of the transcriptional network controlled by the photoreceptor homeobox gene Crx. Curr Biol. 2000;10:301–310. doi: 10.1016/s0960-9822(00)00379-1. [DOI] [PubMed] [Google Scholar] · DOI
- [8]Diaz E, Yang YH, Ferreira T, Loh KC, Okazaki Y, Hayashizaki Y, Tessier-Lavigne M, et al. Analysis of gene expression in the developing mouse retina. Proc Natl Acad Sci USA. 2003;100:5491–5496. doi: 10.1073/pnas.0831080100. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- [9]Rawls JF, Samuel BS, Gordon JI. Gnotobiotic zebrafish reveal evolutionarily conserved responses to the gut microbiota. Proc Natl Acad Sci USA. 2004;101:45964601. doi: 10.1073/pnas.0400706101. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- [10]Leung AY, Mendenhall EM, Kwan TT, Liang R, Eckfeldt C, Chen E, et al. Characterization of expanded intermediate cell mass in zebrafish chordin morphant embryos. Dev Biol. 2005;277:235–254. doi: 10.1016/j.ydbio.2004.09.032. [DOI] [PubMed] [Google Scholar] · DOI
- [11]Malek RL, Sajadi H, Abraham J, Grundy MA, Gerhard GS. The effects of temperature reduction on gene expression and oxidative stress in skeletal muscle from adult zebrafish. Comp Biochem Physiol C Toxicol Pharmacol. 2004;138:363–373. doi: 10.1016/j.cca.2004.08.014. [DOI] [PubMed] [Google Scholar] · DOI
- [12]Meijer AH, Verbeek FJ, Salas-Vidal E, Corredor-Adamez M, Bussman J, van der Sar AM, et al. Transcriptome profiling of adult zebrafish at the late stage of chronic tuberculosis due to Mycobacterium marinum infection. Mol Immunol. 2005;42:1185–1203. doi: 10.1016/j.molimm.2004.11.014. [DOI] [PubMed] [Google Scholar] · DOI
- [13]van der Ven K, De Wit M, Keil D, Moens L, Van Leemput K, Naudts B, et al. Development and application of a brain-specific cDNA microarray for effect evaluation of neuroactive pharmaceuticals in zebrafish (Danio rerio) Comp Biochem Physiol B Biochem Mol Biol. 2005;141:408–417. doi: 10.1016/j.cbpc.2005.05.004. [DOI] [PubMed] [Google Scholar] · DOI
- [14]Ton C, Stamatiou D, Liew CC. Gene expression profile of zebrafish exposed to hypoxia during development. Physiol Genomics. 2003;13:97–106. doi: 10.1152/physiolgenomics.00128.2002. [DOI] [PubMed] [Google Scholar] · DOI
- [15]Linney E, Dobbs-McAuliffe B, Sajadi H, Malek RL. Microarray gene expression profiling during the segmentation phase of zebrafish development. Comp Biochem Physiol C Toxicol Pharmacol. 2004;138:351–362. doi: 10.1016/j.cca.2004.08.008. [DOI] [PubMed] [Google Scholar] · DOI
- [16]Thorpe CJ, Weidinger G, Moon RT. Wnt/beta-catenin regulation of the Sp1-related transcription factor sp5l promotes tail development in zebrafish. Development. 2005;132:1763–1772. doi: 10.1242/dev.01733. [DOI] [PubMed] [Google Scholar] · DOI
- [17]Sumanas S, Jorniak T, Lin S. Identification of novel vascular endothelial-specific genes by the microarray analysis of the zebrafish cloche mutants. Blood. 2005;106:534–541. doi: 10.1182/blood-2004-12-4653. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- [18]Westerfield M. A guide for the laboratory use of zebrafish (Danio rerio) 4. Univ. of Oregon Press; Eugene: 2000. The zebrafish book. [Google Scholar]
- [19]Kimmel CB, Ballard WW, Kimmel SR, Ullmann B, Schilling TF. Stages of embryonic development of the zebrafish. Dev Dyn. 1995;203:253–310. doi: 10.1002/aja.1002030302. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
- [20]Van Gelder RN, von Zastrow ME, Yool A, Dement WC, Barchas JD, Eberwine JH. Amplified RNA synthesized from limited quantities of heterogeneous cDNA. Proc Natl Acad Sci USA. 1990;87:1663–1667. doi: 10.1073/pnas.87.5.1663. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- [21]Irizarry RA, Hobbs B, Collin F, Beazer-Barclay YD, Antonellis KJ, Scherf U, et al. Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics. 2003;4:249–264. doi: 10.1093/biostatistics/4.2.249. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
- [22]Redenti S, Chappell RL. Zinc chelation enhances the zebrafish retinal ERG b-wave. Biol Bull. 2002;203:200–202. doi: 10.2307/1543396. [DOI] [PubMed] [Google Scholar] · DOI
- [23]Masai I, Stemple DL, Okamoto H, Wilson SW. Midline signals regulate retinal neurogenesis in zebrafish. Neuron. 2000;27:251–263. doi: 10.1016/s0896-6273(00)00034-9. [DOI] [PubMed] [Google Scholar] · DOI
- [24]Kay JN, Link BA, Baier H. Staggered cell-intrinsic timing of ath5 expression underlies the wave of ganglion cell neurogenesis in the zebrafish retina. Development. 2005;132:2573–2585. doi: 10.1242/dev.01831. [DOI] [PubMed] [Google Scholar] · DOI
- [25]Link BA, Fadool JM, Malicki J, Dowling JE. The zebrafish young mutation acts non-cell-autonomously to uncouple differentiation from specification for all retinal cells. Development. 2000;127:2177–2188. doi: 10.1242/dev.127.10.2177. [DOI] [PubMed] [Google Scholar] · DOI
- [26]Gregg RG, Willer GB, Fadool JM, Dowling JE, Link BA. Positional cloning of the young mutation identifies an essential role for the Brahma chromatin remodeling complex in mediating retinal cell differentiation. Proc Natl Acad Sci USA. 2003;100:6535–6540. doi: 10.1073/pnas.0631813100. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
Cited by
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Higdon, C. W., Mitra, R. D., & Johnson, S. L. (2013) · PLoS ONE · doi:10.1371/journal.pone.0067801 · Cited by 125 · see citing works
Early retinoic acid deprivation in developing zebrafish results in microphthalmia
LE, H.-G. T., DOWLING, J. E., & CAMERON, D. J. (2012) · Visual Neuroscience · doi:10.1017/s0952523812000296 · Cited by 46 · see citing works
Self-citation
- Authors
- Leung, Y. F., Ma, P., & Dowling, J. E.
- Affiliations
- Harvard University (US)
- University of Illinois Urbana-Champaign (US)
- Venue
- Investigative Opthalmology & Visual Science
- Published
- 2007-02-01
- Volume
- 48
- Issue
- 2
- Pages
- 881
- ISSN
- 0146-0404 (ISSN-L)
- 1552-5783
- PMC
- PMC2663524
- OpenAlex
- W1994968511
- Cited by
- 30
- References
- 0
- Citations by year
- 2026: 2 · 2023: 1 · 2021: 2 · 2020: 1 · 2019: 1 · 2017: 1 · 2014: 3 · 2013: 3 · 2012: 5
- FWCI
- 1.11
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Investigative Ophthalmology & Visual Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Eye Institute (R01EY000811, EY000811)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Zebrafish Biomedical Research Applications
- Keywords
- retinal pigment epithelium, zebrafish embryos, gene expression profiling, eye development
- MeSH terms
- Animals, Embryo, Nonmammalian, Eye Proteins, Pigment Epithelium of Eye, Retina, RNA, Zebrafish, Gene Expression Regulation, Developmental, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Zebrafish Proteins
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