Build me up optic cup: Intrinsic and extrinsic mechanisms of vertebrate eye morphogenesis

Casey, Macaulie A.; Lusk, Sarah; Kwan, Kristen M.

doi:10.1016/j.ydbio.2021.03.023

Cited by 25 publications

(19 citation statements)

References 75 publications

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“…The distal/ventral region expresses retina-specific genes, marking prospective retinal territory, while the dorsal/outer region expresses the transcription factor Otx2, marking prospective retinal pigmented epithelium (RPE) territory ( Bovolenta et al, 1997 ; Fuhrmann, 2010 ; Hatakeyama et al, 2001 ; Hirashima et al, 2008 ). Following a precisely coordinated morphogenesis ( Heermann et al, 2015 ), the OV further forms the two-layered optic cup: the outer layer giving rise to the RPE and the inner layer forming retina populated with mitotically active retinal progenitor cells (reviewed by Casey et al, 2021 ; Chow and Lang, 2001 ; Fuhrmann, 2010 ). Soon after optic cup formation, retinal progenitor cells start to differentiate into seven retinal cell types that together form the structure of the adult retina: retinal ganglion cells, amacrine cells, bipolar cells, Müller glia cells, horizontal cells, and (rod, cone) photoreceptors ( Young, 1985 ; Figure 1a , 4 dpf).…”

Section: Introductionmentioning

confidence: 99%

Fish primary embryonic pluripotent cells assemble into retinal tissue mirroring in vivo early eye development

Zilova

Weinhardt

Tavhelidse

et al. 2021

eLife

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Organoids derived from pluripotent stem cells promise the solution to current challenges in basic and biomedical research. Mammalian organoids are however limited by long developmental time, variable success, and lack of direct comparison to an in vivo reference. To overcome these limitations and address species-specific cellular organization, we derived organoids from rapidly developing teleosts. We demonstrate how primary embryonic pluripotent cells from medaka and zebrafish efficiently assemble into anterior neural structures, particularly retina. Within 4 days, blastula-stage cell aggregates reproducibly execute key steps of eye development: retinal specification, morphogenesis, and differentiation. The number of aggregated cells and genetic factors crucially impacted upon the concomitant morphological changes that were intriguingly reflecting the in vivo situation. High efficiency and rapid development of fish-derived organoids in combination with advanced genome editing techniques immediately allow addressing aspects of development and disease, and systematic probing of impact of the physical environment on morphogenesis and differentiation.

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Section: Introductionmentioning

confidence: 99%

Fish primary embryonic pluripotent cells assemble into retinal tissue mirroring in vivo early eye development

Zilova

Weinhardt

Tavhelidse

et al. 2021

eLife

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“…The main route to understanding development has been the identification of transcription factors (TFs) via the close observation of in vivo retinogenesis. 23,24 Due to the relevance of TFs in RO protocols, the most important ones will be introduced. This is the author's peer reviewed, accepted manuscript.…”

Section: Recapitulating Retina Development In Vitromentioning

confidence: 99%

“…3,5,22 In a transformative way, those provide us with the opportunity to study (retina) development at the cell-, tissueand organ-level in vitro under physiological conditions. 4,23,24 Organoids are generated from embryonic stem cells (ESCs), isolated organ progenitors, or induced pluripotent stem cells (iPSCs) that self-organize into specific tissue types. [2][3][4][5] One central strategy to generate patterns of cell fate in 3D is the spatiotemporal control of transcription factors.…”

Section: Organoids As Accessible Model Systemsmentioning

confidence: 99%

Retina organoids: Window into the biophysics of neuronal systems

2022

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With a kind of magnetism, the human retina draws the eye of neuroscientist and physicist alike. It is attractive as a self-organizing system, which forms as a part of the central nervous system via biochemical and mechanical cues. The retina is also intriguing as an electro-optical device, converting photons into voltages to perform on-the-fly filtering before the signals are sent to our brain. Here, we consider how the advent of stem cell derived in vitro analogs of the retina, termed Retina Organoids, opens up an exploration of the interplay between optics, electrics and mechanics in a complex neuronal network, all in a Petri dish. This review presents state-of-the-art retina organoid protocols by emphasizing links to the biochemical and mechanical signals of in vivo retinogenesis. Electrophysiological recording of active signal processing becomes possible as retina organoids generate light sensitive and synaptically connected photoreceptors. Experimental biophysical tools provide data to steer the development of mathematical models operating at different levels of coarse-graining. In concert, they provide a means to study how mechanical factors guide retina self-assembly. In turn, this understanding informs the engineering of mechanical signals required to tailor the growth of neuronal network morphology. Tackling the complex developmental and computational processes in the retina requires an interdisciplinary endeavor combining experiment and theory, physics and biology. The reward is enticing: in the next few years, retina organoids could offer a glimpse inside the machinery of simultaneous cellular self-assembly and signal processing, all in an in vitro setting.

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“…These optic vesicle structures undergo precise morphogenetic events, including invagination, to form the bilayered optic cup, consisting of neural retina and retinal pigment epithelium. During this process, the connection between the optic vesicle and developing brain is constricted, forming the optic stalk, which initially serves to tether the eye and brain 1‐8 . Concurrent with invagination is the formation of the optic fissure: two margins of neural retina and RPE form at the ventral surface of the optic cup and extend through the stalk, creating a narrow cleft.…”

Section: Introductionmentioning

confidence: 99%

“…During this process, the connection between the optic vesicle and developing brain is constricted, forming the optic stalk, which initially serves to tether the eye and brain. [1][2][3][4][5][6][7][8] Concurrent with invagination is the formation of the optic fissure: two margins of neural retina and RPE form at the ventral surface of the optic cup and extend through the stalk, creating a narrow cleft. This seam-like structure subsequently fuses along its proximodistal length to create an essential conduit used by vasculature cells to enter the eye, and retinal ganglion cell axons to exit the eye and connect with the brain.…”

Section: Introductionmentioning

confidence: 99%

Pax2a, but not pax2b, influences cell survival and periocular mesenchyme localization to facilitate zebrafish optic fissure closure

Lusk

Kwan

2021

Developmental Dynamics

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Background: Pax2 is required for optic fissure development in many organisms, including humans and zebrafish. Zebrafish loss-of-function mutations in pax2a display coloboma, yet the etiology of the morphogenetic defects is unclear. Further, pax2 is duplicated in zebrafish, and a role for pax2b in optic fissure development has not been examined. Results: Using a combination of imaging and molecular genetics, we interrogated a potential role for pax2b and examined how loss of pax2 affects optic fissure development. Although optic fissure formation appears normal in pax2 mutants, an endothelial-specific subset of periocular mesenchyme (POM) fails to initially localize within the optic fissure, yet both neural crest and endothelial-derived POM ectopically accumulate at later stages in pax2a and pax2a; pax2b mutants. Apoptosis is not up-regulated within the optic fissure in pax2 mutants, yet cell death is increased in tissues outside of the optic fissure, and when apoptosis is inhibited, coloboma is partially rescued. In contrast to pax2a, loss of pax2b does not appear to affect optic fissure morphogenesis. Conclusions: Our results suggest that pax2a, but not pax2b, supports cell survival outside of the optic fissure and POM abundance within it to facilitate optic fissure closure.

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Build me up optic cup: Intrinsic and extrinsic mechanisms of vertebrate eye morphogenesis

Cited by 25 publications

References 75 publications

Fish primary embryonic pluripotent cells assemble into retinal tissue mirroring in vivo early eye development

Fish primary embryonic pluripotent cells assemble into retinal tissue mirroring in vivo early eye development

Retina organoids: Window into the biophysics of neuronal systems

Pax2a, but not pax2b, influences cell survival and periocular mesenchyme localization to facilitate zebrafish optic fissure closure

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