Soluble factors and the development of rod photoreceptors

Levine, Edward M.; Fuhrmann, Sabine; Reh, Thomas A.

doi:10.1007/pl00000686

Cited by 98 publications

(70 citation statements)

References 74 publications

(85 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The application of RA at later stages of development promoted rod differentiation while it inhibited cone maturation consistent with other models on the role of RA in photoreceptor cell development (Hyatt et al, 1996a;Levine et al, 2000).…”

Section: Chemical Screenssupporting

confidence: 89%

Zebrafish: A model system for the study of eye genetics

Fadool

Dowling

2008

Progress in Retinal and Eye Research

193

172

View full text Add to dashboard Cite

Over the last decade, the use of the zebrafish as a genetic model has moved beyond the proof-ofconcept for the analysis of vertebrate embryonic development to demonstrated utility as a mainstream model organism for the understanding of human disease. The initial identification of a variety of zebrafish mutations affecting the eye and retina, and the subsequent cloning of mutated genes have revealed cellular, molecular and physiological processes fundamental to visual system development. With the increasing development of genetic manipulations, sophisticated techniques for phenotypic characterization, behavioral approaches and screening strategies, the identification of novel genes or novel gene functions will have important implications for our understanding of human eye diseases, pathogenesis, and treatment.

show abstract

Section: Chemical Screenssupporting

confidence: 89%

Zebrafish: A model system for the study of eye genetics

Fadool

Dowling

2008

Progress in Retinal and Eye Research

193

172

View full text Add to dashboard Cite

show abstract

“…Numerous soluble factors have been implicated in the differentiation of rods and cones (29,30), yet as a TF, we would predict that tbx2b functions cell-autonomously in photoreceptor cell specification. To test this hypothesis, we generated genetic chimeras between WT and tbx2b p25bbtl mutant embryos (31).…”

Section: Resultsmentioning

confidence: 97%

Tbx2b is required for ultraviolet photoreceptor cell specification during zebrafish retinal development

Álvarez-Delfín

Morris

Snelson

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

136

View full text Add to dashboard Cite

The vertebrate rod and cone photoreceptors are highly specialized sensory neurons that transduce light into the chemical and electrical signals of the nervous system. Although the physiological properties of cones and rods are well known, only a handful of genes have been identified that regulate the specification of photoreceptor subtypes. Taking advantage of the mosaic organization of photoreceptors in zebrafish, we report the isolation of a mutation resulting in a unique change in photoreceptor cell fate. Mutation of the lots-of-rods (lor) locus results in a near one-for-one transformation of UV-cone precursors into rods. The transformed cells exhibit morphological characteristics and a gene-expression pattern typical of rods, but differentiate in a temporal and spatial pattern consistent with UV-cone development. In mutant larvae and adults, the highly ordered photoreceptor mosaic is maintained and degeneration is not observed, suggesting that lor functions after the specification of the other photoreceptor subtypes. In genetic chimeras, lor functions cell-autonomously in the specification of photoreceptor cell fate. Linkage analysis and geneticcomplementation testing indicate that lor is an allele of tbx2b/fby (from beyond). fby was identified by a pineal complex phenotype, and carries a nonsense mutation in the T-box domain of the tbx2b transcription factor. Homozygous fby mutant larvae and lor/fby transheterozygotes also display the lots-of-rods phenotype. Based upon these data, we propose a previously undescribed function for tbx2b in photoreceptor cell precursors, to promote the UV cone fate by repressing the rod differentiation pathway.cone ͉ Danio rerio ͉ T-box ͉ mosaic V ertebrates have evolved 2 major classes of retinal photoreceptors: rods, which mediate dim light vision, and cones, which detect light of greater intensity, have a faster temporal resolution, and mediate color vision. Largely from the analysis of mutations in mice and humans, a transcriptional network regulating photoreceptor cell development has been proposed. The presumptive photoreceptor progenitors sequentially express the homeobox transcription factors (TFs) Otx2 and Crx (1-3), and in their absence, photoreceptor precursors are not specified or fail to differentiate. Rod specification requires the additional expression of the Maf-family TF Nrl and its target Nr2e3 (4, 5). Nrl acts as a molecular switch; in its absence, precursors adopt the short-wavelength (S) opsin cone fate (5, 6), and mis-and over-expression of Nrl transforms most if not all cone precursors into functional rods (7,8). NR2E3 expression, which is disrupted in enhanced S-cone syndrome in humans and the rd7 mouse, is required for the repression of cone-specific genes in rod precursors (4, 9, 10). However, it remains to be determined if a reciprocal system exists in cone precursors for repressing rodspecific genes.The zebrafish retina, in addition to rods, possesses 4 cone subtypes, each with a distinct morphology and expressing a unique opsin (11-17). The spatial...

show abstract

“…By day 11, BrdU-labeled cells in the ONL rarely expressed rhodopsin, a marker for rod photoreceptors (15.5 Ϯ 3.8% of BrdU-labeled cells). To promote differentiation of progenitor-like cells into photoreceptor cells, we tested the effects of RA on these cells, because RA is crucial for photoreceptor genesis (Hyatt and Dowling, 1997;Levine et al, 2000). Application of RA (0.3 M) for 7 d after Wnt3a treatment increased the number of BrdU-labeled cells positive for the early photoreceptor precursor marker Crx (Chen et al, 1997;Furukawa et al, 1997) (Fig.…”

Section: Müller Glia-derived Progenitors Differentiate Into Photorecementioning

confidence: 99%