Retinal stem cells and regeneration

Moshiri, Ala; Close, Jennie; Reh, Thomas A.

doi:10.1387/ijdb.041870am

Cited by 150 publications

(126 citation statements)

References 90 publications

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“…In vertebrate retina, eyes grow by adding new cells to the peripheral zones, and the peripheral cells are developmentally younger than central cells (25). In fish, the eyes continue to grow through the lifetime by adding new cells to the peripheral zones (26), resulting in a larger gradient of developmental timing in the fish retina than in the primate retina. The peripheral cells have a longer history of cell divisions and have gone through a longer history in chromatin remodeling for transcriptional regulation than central cells in the retina.…”

Section: Discussionmentioning

confidence: 99%

Identification of a locus control region for quadruplicated green-sensitive opsin genes in zebrafish

Tsujimura

Chinen

Kawamura

2007

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

113

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Duplication of opsin genes has a crucial role in the evolution of visual system. Zebrafish have four green-sensitive (RH2) opsin genes (RH2-1, RH2-2, RH2-3, and RH2-4) arrayed in tandem. They are expressed in the short member of the double cones (SDC) but differ in expression areas in the retina and absorption spectra of their encoding photopigments. The shortest and the second shortest wavelength subtypes, RH2-1 and RH2-2, are expressed in the central-to-dorsal retina. The longer wavelength subtype, RH2-3, is expressed circumscribing the RH2-1/RH2-2 area, and the longest subtype, RH2-4, is expressed further circumscribing the RH2-3 area and mainly occupying the ventral retina. The present report shows that a 0.5-kb region located 15 kb upstream of the RH2 gene array is an essential regulator for their expression. When the 0.5-kb region was deleted from a P1-artificial chromosome (PAC) clone encompassing the four RH2 genes and when one of these genes was replaced with a reporter GFP gene, the GFP expression in SDCs was abolished in the zebrafish to which a series of the modified PAC clones were introduced. Transgenic studies also showed that the 0.5-kb region conferred the SDC-specific expression for promoters of a non-SDC (UV opsin) and a nonretinal (keratin 8) gene. Changing the location of the 0.5-kb region in the PAC clone conferred the highest expression for its proximal gene. The 0.5-kb region was thus designated as RH2-LCR analogous to the locus control region of the L-M opsin genes of primates.gene duplication ͉ GFP reporter ͉ transgenesis F unctional differentiation of duplicated genes is important for organismal evolution and is achieved through modifications of not only coding regions but also regulatory mechanisms of the gene expression in the duplicates. The regulatory mechanism for the spatial and the temporal coordination of gene expression among duplicated genes has been a subject of intense interest (1, 2). Gene duplications have an essential role in the evolution of the visual system. The visual opsins in vertebrates are classified into five phylogenetic types that originated before the vertebrate radiation: rod opsin or rhodopsin (RH1); RH1-like, or green cone opsin (RH2); short wavelength-sensitive type 1, or UV-blue cone opsin (SWS1); short wavelength-sensitive type 2, or blue cone opsin (SWS2); and middle-to long-wavelength-sensitive, or redgreen cone opsin (M/LWS) (3). However, the understanding of the regulatory mechanisms for the differential expression among the five types is still fragmentary. Subtypes of the visual opsins, created by more recent gene duplications, provide an excellent model to study the regulatory evolution of duplicated genes. A well documented example is the locus control region (LCR) of the L-M opsin genes (subtypes of M/LWS) arrayed on the X chromosome in the catarrhine primates (Old World monkeys, apes, and humans) (4).The primate L-M opsin LCR is located at Ϸ3.5 kb upstream of the gene array and interacts with only the most proximal or the second proximal gene o...

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Section: Discussionmentioning

confidence: 99%

Identification of a locus control region for quadruplicated green-sensitive opsin genes in zebrafish

Tsujimura

Chinen

Kawamura

2007

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

113

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“…Instead, the ciliary body develops from two layers of neuroepithelial cells at the periphery of the optic cup (Beebe, 1986). The pigmented outer layer of the ciliary epithelium has been proposed to contain retinal stem cells (Ahmad et al, 2000;Tropepe et al, 2000;Moshiri et al, 2004;Coles et al, 2006;Cicero et al, 2009), however, the ciliary body does not appear to give rise to neurons in vivo (Moshiri et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Loss of adenomatous polyposis coli (apc) results in an expanded ciliary marginal zone in the zebrafish eye

Stephens

Senecal

Nguyen

et al. 2010

Developmental Dynamics

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The distal region of neural retina (ciliary marginal zone [CMZ]) contains stem cells that produce non-neural and neuronal progenitors. We provide a detailed gene expression analysis of the eyes of apc mutant zebrafish where the Wnt/b-catenin pathway is constitutively active. Wnt/b-catenin signaling leads to an expansion of the CMZ accompanied by a central shift of the retinal identity gene sox2 and the proneural gene atoh7. This suggests an important role for peripheral Wnt/b-catenin signaling in regulating the expression and localization of neurogenic genes in the central retina. Retinal identity genes rx1 and vsx2, as well as meis1 and pax6a act upstream of Wnt/b-catenin pathway activation. Peripheral cells that likely contain stem cells can be identified by the expression of follistatin, otx1, and axin2 and the lack of expression of myca and cyclinD1. Our results introduce the zebrafish apc mutation as a new model to study signaling pathways regulating the CMZ.

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“…In this case, the CSB-deficient mouse would have higher steady-state levels of oxidative DNA damage, which would result in slower transcription rates with a higher (stochastic) risk of stalling RNA polymerase II and subsequent induction of apoptosis. Since retinal photoreceptors are postmitotic cells and are not replaced by dormant stem/progenitor cells (36), analysis of the kinetics of cell loss might discriminate between the two models. Curve fitting on the data set provided in Fig.…”

Section: Discussionmentioning

confidence: 99%

Retinal Degeneration and Ionizing Radiation Hypersensitivity in a Mouse Model for Cockayne Syndrome

Gorgels

Pluijm

Brandt

et al. 2007

Molecular and Cellular Biology

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Mutations in the CSB gene cause Cockayne syndrome (CS), a DNA repair disorder characterized by UV sensitivity and severe physical and neurological impairment. CSB functions in the transcription-coupled repair subpathway of nucleotide excision repair. This function may explain the UV sensitivity but hardly clarifies the other CS symptoms. Many of these, including retinopathy, are associated with premature aging. We studied eye pathology in a mouse model for CS. Csb m/m mice were hypersensitive to UV light and developed epithelial hyperplasia and squamous cell carcinomas in the cornea, which underscores the importance of transcriptioncoupled repair of photolesions in the mouse. In addition, we observed a spontaneous loss of retinal photoreceptor cells with age in the Csb m/m retina, resulting in a 60% decrease in the number of rods by the age of 18 months. Importantly, when Csb m/m mice (as well as Csa ؊/؊ mice) were exposed to 10 Gy of ionizing radiation, we noticed an increase in apoptotic photoreceptor cells, which was not observed in wild-type animals. This finding, together with our observation that the expression of established oxidative stress marker genes is upregulated in the Csb m/m retina, suggests that (endogenous) oxidative DNA lesions play a role in this CS-specific premature-aging feature and supports the oxidative DNA damage theory of aging.

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Retinal stem cells and regeneration

Cited by 150 publications

References 90 publications

Identification of a locus control region for quadruplicated green-sensitive opsin genes in zebrafish

Identification of a locus control region for quadruplicated green-sensitive opsin genes in zebrafish

Loss of adenomatous polyposis coli (apc) results in an expanded ciliary marginal zone in the zebrafish eye

Retinal Degeneration and Ionizing Radiation Hypersensitivity in a Mouse Model for Cockayne Syndrome

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