The bHLH Transcription Factor NeuroD Governs Photoreceptor Genesis and Regeneration Through Delta-Notch Signaling

Taylor, Scott M.; Álvarez-Delfín, Karen; Saade, Carole J.; Thomas, Jessica; Thummel, Ryan; Fadool, James M.; Hitchcock, Peter F.

doi:10.1167/iovs.15-17616

Cited by 46 publications

(52 citation statements)

References 96 publications

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“…2) 20,24 , a number of studies have also indicated an increased expression of Notch signaling components in injury-responsive Müller glia 20,26,27 . One study suggests Notch signaling stimulates proliferation of progenitors destined to regenerate photoreceptors 28 , while another showed this signaling enhances progenitor differentiation 20 . We favor the idea that Notch signaling helps maintain Müller glia in a differentiated state and contributes to progenitor differentiation, while Notch signaling inhibition facilitates Müller glia reprogramming and proliferation in response to retinal cell death.…”

Section: Signaling Mechanisms Underlying Müller Glia Reprogramming Anmentioning

confidence: 99%

Retina regeneration in zebrafish

Wei

Goldman

2016

Current Opinion in Genetics & Development

208

212

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Unlike mammals, zebrafish are able to regenerate a damaged retina. Key to this regenerative response are Müller glia that respond to retinal injury by undergoing a reprogramming event that allows them to divide and generate a retinal progenitor that is multipotent and responsible for regenerating all major retinal neuron types. The fish and mammalian retina are composed of similar cell types with conserved function. Because of this it is anticipated that studies of retina regeneration in fish may suggest strategies for stimulating Müller glia reprogramming and retina regeneration in mammals. In this review we describe recent advances and future directions in retina regeneration research using zebrafish as a model system.

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Section: Signaling Mechanisms Underlying Müller Glia Reprogramming Anmentioning

confidence: 99%

Retina regeneration in zebrafish

Wei

Goldman

2016

Current Opinion in Genetics & Development

208

212

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“…Their data suggested that NeuroD is a regulator of Notch signaling, confirming its important role in photoreceptor regeneration. [53] By using both classical genetic techniques such as morpholino knockdown as well as CRISPR-Cas genome editing, the findings of this study were strengthened by the rigorous experimental design.…”

Section: Advances In Ocular Genetics Using Crispr-cas Genome Editing mentioning

confidence: 92%

“…Taylor et al induced mutations in the gene NeuroD , a potential player in retinal regeneration in zebrafish, via CRISPR-Cas genome editing. [53] The group targeted NeuroD using sgRNA and SpCas9 to induce deleterious mutations in zebrafish embryos, and they also suppressed the gene using morpholinos oligonucleotides to provide a point of comparison. Their data suggested that NeuroD is a regulator of Notch signaling, confirming its important role in photoreceptor regeneration.…”

Section: Advances In Ocular Genetics Using Crispr-cas Genome Editing mentioning

confidence: 99%

CRISPR applications in ophthalmologic genome surgery

Cabral

DiCarlo

Justus

et al. 2017

Current Opinion in Ophthalmology

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Purpose of review This review seeks to summarize and discuss the application of CRISPR-Cas systems for genome editing, also called “genome surgery,” in the field of ophthalmology. Recent findings Precision medicine is an emerging approach for disease treatment and prevention that takes into account the variability of an individual’s genetic sequence. Various groups have used CRISPR-Cas genome editing to make significant progress in mammalian preclinical models of eye disease, the basic science of eye development in zebrafish, the in vivo modification of ocular tissue, as well as the correction of stem cells with therapeutic applications. Additionally, investigators have creatively used the targeted mutagenic potential of CRISPR-Cas systems to target pathogenic alleles in vitro. Summary Over the past year, CRISPR-Cas genome editing has been used to correct pathogenic mutations in vivo as well as in transplantable stem cells. While off-target mutagenesis remains a concern, improvement in CRISPR-Cas technology and careful screening for undesired mutations will likely lead to clinical eye therapeutics employing CRISPR-Cas systems in the near future.

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“…To determine the expression levels of genes that regulate cell cycle, Quantitative Real‐Time PCR was performed as previously described (Taylor et al, ). For each condition, three biological replicates of 50 embryo heads were collected.…”

Section: Methodsmentioning

confidence: 99%

Progranulin regulates neurogenesis in the developing vertebrate retina

Walsh

Hitchcock

2017

Developmental Neurobiology

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We evaluated the expression and function of the microglia-specific growth factor, Progranulin-a (Pgrn-a) during developmental neurogenesis in the embryonic retina of zebrafish. At 24 hpf pgrn-a is expressed throughout the forebrain, but by 48 hpf pgrn-a is exclusively expressed by microglia and/or microglial precursors within the brain and retina. Knockdown of Pgrn-a does not alter the onset of neurogenic programs or increase cell death, however, in its absence, neurogenesis is significantly delayed - retinal progenitors fail to exit the cell cycle at the appropriate developmental time and postmitotic cells do not acquire markers of terminal differentiation, and microglial precursors do not colonize the retina. Given the link between Progranulin and cell cycle regulation in peripheral tissues and transformed cells, we analyzed cell cycle kinetics among retinal progenitors following Pgrn-a knockdown. Depleting Pgrn-a results in a significant lengthening of the cell cycle. These data suggest that Pgrn-a plays a dual role during nervous system development by governing the rate at which progenitors progress through the cell cycle and attracting microglial progenitors into the embryonic brain and retina. Collectively, these data show that Pgrn-a governs neurogenesis by regulating cell cycle kinetics and the transition from proliferation to cell cycle exit and differentiation.

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The bHLH Transcription Factor NeuroD Governs Photoreceptor Genesis and Regeneration Through Delta-Notch Signaling

Cited by 46 publications

References 96 publications

Retina regeneration in zebrafish

Retina regeneration in zebrafish

CRISPR applications in ophthalmologic genome surgery

Progranulin regulates neurogenesis in the developing vertebrate retina

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