Thyroid hormone signaling specifies cone photoreceptor subtypes during eye development: Insights from model organisms and human stem cell-derived retinal organoids

McNerney, Christina; Johnston, Robert J.

doi:10.1016/bs.vh.2021.03.001

Cited by 24 publications

(12 citation statements)

References 164 publications

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“…In the absence of thyroid hormone, THRB is bound by corepressors. When thyroid hormone is present, it binds THRB, which induces the replacement of corepressors by coactivators, ultimately regulating gene expression ( McNerney and Johnston, 2021 ). Thyroid hormone receptors can homodimerize or heterodimerize with retinoid X receptor gamma (RXRG), a nuclear receptor expressed in cones ( Mori et al, 2001 ), to regulate aspects of cone subtype specification ( Roberts et al, 2005 ).…”

Section: Photoreceptor Subtype Specificationmentioning

confidence: 99%

“…Thyroid hormone signaling regulates the first choice between S and M/L cone fates. Thyroid hormone has two main forms: the active form, T3, which binds with high affinity to thyroid hormone receptors, and T4, the less active, circulating form ( Samuels et al, 1974 ; Schroeder and Privalsky, 2014 ; McNerney and Johnston, 2021 ). Thyroid hormones cannot diffuse freely across cell membranes but rather require transporters such as MCT8 ( Dumitrescu et al, 2004 ; Friesema et al, 2004 ).…”

Section: Photoreceptor Subtype Specificationmentioning

confidence: 99%

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Patterning and Development of Photoreceptors in the Human Retina

Hussey

Hadyniak

Johnston

2022

Front. Cell Dev. Biol.

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Humans rely on visual cues to navigate the world around them. Vision begins with the detection of light by photoreceptor cells in the retina, a light-sensitive tissue located at the back of the eye. Photoreceptor types are defined by morphology, gene expression, light sensitivity, and function. Rod photoreceptors function in low-light vision and motion detection, and cone photoreceptors are responsible for high-acuity daytime and trichromatic color vision. In this review, we discuss the generation, development, and patterning of photoreceptors in the human retina. We describe our current understanding of how photoreceptors are patterned in concentric regions. We conclude with insights into mechanisms of photoreceptor differentiation drawn from studies of model organisms and human retinal organoids.

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Section: Photoreceptor Subtype Specificationmentioning

confidence: 99%

Section: Photoreceptor Subtype Specificationmentioning

confidence: 99%

Patterning and Development of Photoreceptors in the Human Retina

Hussey

Hadyniak

Johnston

2022

Front. Cell Dev. Biol.

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“…Besides genes involved in the circulatory system development and extracellular matrix/cell motility (see “ Gene set enrichment analysis ” section below) we identified two differentially expressed genes of interest. The first, DIO2 , is involved in sensitive periods 66 , 67 and in the development of the retina in the chicken and other vertebrates 68 . The second, PAX2 , is a transcription factor that plays an important role in the glia during retinal development in the chicken embryo 86 and in eye development in vertebrates 87 .…”

Section: Resultsmentioning

confidence: 99%

“…DIO2 is a thyroid hormone converting enzyme with an essential role in neurodevelopment and the regulation of the sensitive periods in mammals and birds 66 . DIO2 has a role in the development of the retina in different vertebrates, including the chicken, where is involved in spatiotemporally specified waves of cone differentiation 68 . In the chick retina, the expression of thyroid hormone regulators follows a series of spatiotemporal waves, moving from the central retina to the periphery.…”

Section: Discussionmentioning

confidence: 99%

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Light-induced asymmetries in embryonic retinal gene expression are mediated by the vascular system and extracellular matrix

Versace

Sgadò

George

et al. 2022

Sci Rep

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Left–right asymmetries in the nervous system (lateralisation) influence a broad range of behaviours, from social responses to navigation and language. The role and pathways of endogenous and environmental mechanisms in the ontogeny of lateralisation remains to be established. The domestic chick is a model of both endogenous and experience-induced lateralisation driven by light exposure. Following the endogenous rightward rotation of the embryo, the asymmetrical position in the egg results in a greater exposure of the right eye to environmental light. To identify the genetic pathways activated by asymmetric light stimulation, and their time course, we exposed embryos to different light regimes: darkness, 6 h of light and 24 h of light. We used RNA-seq to compare gene expression in the right and left retinas and telencephalon. We detected differential gene expression in right vs left retina after 6 h of light exposure. This difference was absent in the darkness condition and had already disappeared by 24 h of light exposure, suggesting that light-induced activation is a self-terminating phenomenon. This transient effect of light exposure was associated with a downregulation of the sensitive-period mediator gene DIO2 (iodothyronine deiodinase 2) in the right retina. No differences between genes expressed in the right vs. left telencephalon were detected. Gene networks associated with lateralisation were connected to vascularisation, cell motility, and the extracellular matrix. Interestingly, we know that the extracellular matrix—including the differentially expressed PDGFRB gene—is involved in morphogenesis, sensitive periods, and in the endogenous chiral mechanism of primary cilia, that drives lateralisation. Our data show a similarity between endogenous and experience-driven lateralisation, identifying functional gene networks that affect lateralisation in a specific time window.

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AOP Report: Thyroperoxidase Inhibition Leading to Altered Visual Function in Fish Via Altered Retinal Layer Structure

Gölz

Baumann

Pannetier

et al. 2022

Enviro Toxic and Chemistry

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Thyroid hormones (THs) are involved in the regulation of many important physiological and developmental processes, including vertebrate eye development. Thyroid hormone system–disrupting chemicals (THSDCs) may have severe consequences, because proper functioning of the visual system is a key factor for survival in wildlife. However, the sequence of events leading from TH system disruption (THSD) to altered eye development in fish has not yet been fully described. The development of this adverse outcome pathway (AOP) was based on an intensive literature review of studies that focused on THSD and impacts on eye development, mainly in fish. In total, approximately 120 studies (up to the end of 2021) were used in the development of this AOP linking inhibition of the key enzyme for TH synthesis, thyroperoxidase (TPO), to effects on retinal layer structure and visual function in fish (AOP‐Wiki, AOP 363). In a weight‐of‐evidence evaluation, the confidence levels were overall moderate, with ample studies showing the link between reduced TH levels and altered retinal layer structure. However, some uncertainties about the underlying mechanism(s) remain. Although the current weight‐of‐evidence evaluation is based on fish, the AOP is plausibly applicable to other vertebrate classes. Through the re‐use of several building blocks, this AOP is connected to the AOPs leading from TPO and deiodinase inhibition to impaired swim bladder inflation in fish (AOPs 155–159), together forming an AOP network describing THSD in fish. This AOP network addresses the lack of thyroid‐related endpoints in existing fish test guidelines for the evaluation of THSDCs. Environ Toxicol Chem 2022;41:2632–2648. © 2022 SETAC

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Thyroid hormone signaling specifies cone photoreceptor subtypes during eye development: Insights from model organisms and human stem cell-derived retinal organoids

Cited by 24 publications

References 164 publications

Patterning and Development of Photoreceptors in the Human Retina

Patterning and Development of Photoreceptors in the Human Retina

Light-induced asymmetries in embryonic retinal gene expression are mediated by the vascular system and extracellular matrix

AOP Report: Thyroperoxidase Inhibition Leading to Altered Visual Function in Fish Via Altered Retinal Layer Structure

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