Cell differentiation in the retina of the mouse

Young, Richard W.

doi:10.1002/ar.1092120215

Cited by 991 publications

(966 citation statements)

References 11 publications

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“…The expression of IRBP in the retina starts at E13 and continues to be expressed after birth in both rod-and cone cells of the postmitotic photoreceptor layer as well as the pineal gland (al-Ubaidi et al, 1992a;Yokoyama et al, 1992). All the cone cells are generated between E12 ± 15 of embryogenesis, while the majority of rod cells di erentiate after birth (Carter-Dawson and LaVail, 1979;Young, 1985). IRBP-Cre; Rb/¯oxed mice were crossed with p107 and p53 mutant mice to obtain compound mutants carrying all combinations.…”

Section: Tissue-speci®c Rb Inactivationmentioning

confidence: 99%

Developmental defects and tumor predisposition in Rb mutant mice

Vooijs

Berns

1999

Oncogene

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Section: Tissue-speci®c Rb Inactivationmentioning

confidence: 99%

Developmental defects and tumor predisposition in Rb mutant mice

Vooijs

Berns

1999

Oncogene

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“…When assaying photoreceptor cis-regulatory activity, electroporation is usually performed in newborn mice (postnatal day 0, P0) which is the time of peak rod production [11][12] . Once retinal cell types become post-mitotic, electroporation is much less efficient.…”

Section: Introductionmentioning

confidence: 99%

Quantifying the Activity of cis-Regulatory Elements in the Mouse Retina by Explant Electroporation

Montana

Myers

Corbo

2012

Methods in Molecular Biology

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Transcription factors within cellular gene networks control the spatiotemporal pattern and levels of expression of their target genes by binding to cis-regulatory elements (CREs), short (˜300-600 bp) stretches of genomic DNA which can lie upstream, downstream, or within the introns of the genes they control. CREs (i.e., enhancers/promoters) typically consist of multiple clustered binding sites for both transcriptional activators and repressors 1-3 . They serve as logical integrators of transcriptional input giving a unitary output in the form of spatiotemporally precise and quantitatively exact promoter activity. Most studies of mammalian cis-regulation to date have relied on mouse transgenesis as a means of assaying the enhancer function of CREs 4-5 . This technique is time-consuming, costly and, on account of insertion site effects, largely non-quantitative. On the other hand, quantitative assays for mammalian CRE function have been developed in tissue culture systems (e.g., dual luciferase assays), but the in vivo relevance of these results is often uncertain.Electroporation offers an excellent alternative to traditional mouse transgenesis in that it permits both spatiotemporal and quantitative assessment of cis-regulatory activity in living mammalian tissue. This technique has been particularly useful in the analysis of cis-regulation in the central nervous system, especially in the cerebral cortex and the retina 6-8 . While mouse retinal electroporation, both in vivo and ex vivo, has been developed and extensively described by Matsuda and Cepko 6-7,9 , we have recently developed a simple approach to quantify the activity of photoreceptor-specific CREs in electroporated mouse retinas 10 . Given that the amount of DNA that is introduced into the retina by electroporation can vary from experiment to experiment, it is necessary to include a co-electroporated 'loading control' in all experiments. In this respect, the technique is very similar to the dual luciferase assay used to quantify promoter activity in cultured cells.When assaying photoreceptor cis-regulatory activity, electroporation is usually performed in newborn mice (postnatal day 0, P0) which is the time of peak rod production [11][12] . Once retinal cell types become post-mitotic, electroporation is much less efficient. Given the high rate of rod birth in newborn mice and the fact that rods constitute more than 70% of the cells in the adult mouse retina, the majority of cells that are electroporated at P0 are rods. For this reason, rod photoreceptors are the easiest retinal cell type to study via electroporation. The technique we describe here is primarily useful for quantifying the activity of photoreceptor CREs. (Fig. 2A). The metal rails should be completely sealed to the bottom of the slide. 2. Use a Dremel tool to cut a handle off a plastic microcentrifuge tube rack. Cut the handle into 5 small rectangular pieces each with the following dimensions: length 0.8cm, height 0.6cm, width 0.3cm (Fig. 2B). These plastic pieces are reusable spa...

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“…In rodents, about 73% of retinal neurons are photoreceptor cells (Young, 1985). Rods and cones, the two types of photoreceptors in the retina, show a species-specific ratio and spatial distribution.…”

Section: Introductionmentioning

confidence: 99%

“…For photoreceptor cells, cones are usually born (exit from the mitotic cycle and commit to the photoreceptor lineage) earlier than rods. In rodents, cones are born on embryonic days E11.5-E18.5, while rods are born in a longer period from E12.5 to postnatal day 7 (P7) with a peak at P0 (Carter-Dawson and LaVail, 1979;Young, 1985). However, there is a significant delay, several days in rodents, for newly born photoreceptor precursors to begin expressing the specific type of opsin and other genes that confer the mature phenotype (Watanabe and Raff, 1990;Cepko, 1996).…”

Section: Introductionmentioning

confidence: 99%

Regulation of photoreceptor gene expression by Crx-associated transcription factor network

2008

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Rod and cone photoreceptors in the mammalian retina are special types of neurons that are responsible for phototransduction, the first step of vision. Development and maintenance of photoreceptors require precisely regulated gene expression. This regulation is mediated by a network of photoreceptor transcription factors centered on Crx, an Otx-like homeodomain transcription factor. The cell type (subtype) specificity of this network is governed by factors that are preferentially expressed by rods or cones or both, including the rod-determining factors neural retina leucine zipper protein (Nrl) and the orphan nuclear receptor Nr2e3; and cone-determining factors, mostly nuclear receptor family members. The best-documented of these include thyroid hormone receptor β2 (Trβ2), retinoid related orphan receptor Rorβ, and retinoid X receptor Rxrγ. The appropriate function of this network also depends on general transcription factors and co-factors that are ubiquitously expressed, such as the Sp zinc finger transcription factors and STAGA coactivator complexes. These cell type-specific and general transcription regulators form complex interactomes; mutations that interfere with any of the interactions can cause photoreceptor development defects or degeneration. In this manuscript, we review recent progress on the roles of various photoreceptor transcription factors and interactions in photoreceptor subtype development. We also provide evidence of auto-, para-, and feedback regulation among these factors at the transcriptional level. These protein-protein and protein-promoter interactions provide precision and specificity in controlling photoreceptor subtype-specific gene expression, development and survival. Understanding these interactions may provide insights to more effective therapeutic interventions for photoreceptor diseases.

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Cell differentiation in the retina of the mouse

Cited by 991 publications

References 11 publications

Developmental defects and tumor predisposition in Rb mutant mice

Developmental defects and tumor predisposition in Rb mutant mice

Quantifying the Activity of cis-Regulatory Elements in the Mouse Retina by Explant Electroporation

Regulation of photoreceptor gene expression by Crx-associated transcription factor network

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