Neural specification, targeting, and circuit formation during visual system assembly

Malin, Jennifer A; Desplan, Claude

doi:10.1073/pnas.2101823118

Cited by 21 publications

(13 citation statements)

References 199 publications

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“…64 Several cell type specific TFs that determine cell fate specification have been investigated on a genetic and transcriptomic level, 8, 67-72 and reviewed in depth. [73][74][75][76][77] In RO culture, the layers of the NR can be generated, although the curvature of the layers is opposite to the in vivo version. Some cell lines are also unable to form ROs 46,51,[78][79][80] which is suspected to be due to epigenetic preprogramming dependence on the stem cell source.…”

Section: Recapitulating Retina Development In Vitromentioning

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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Section: Recapitulating Retina Development In Vitromentioning

confidence: 99%

Retina organoids: Window into the biophysics of neuronal systems

2022

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“…Although the drosophila visual system is morphologically and structurally different from the vertebrate one, many parallels can be described ( Figure 2 ). Drosophila captures visual information by the retina and processes it through the optic lobes [ 34 , 35 ]. Each optic lobe consists of four distinct neuropiles: Lamina, Medulla, Lobula, and Lobula plate.…”

Section: Alternative Organism Models For Retina Neuroregenerationmentioning

confidence: 99%

“…Like in mammals, glia plays a complex homeostatic role in the nervous system of flies, being in close morphological and functional connection with neurons. During the visual system development of drosophila, glial cells are crucial in mediating neural circuit assembly and forming boundaries [ 35 , 42 ], while in the mature visual system, they have a pivotal role in synaptic transmission and visual processing [ 41 ]. In flies, non-neuronal ommatidial cone cells (CC) support retinal neuronal cells and share structural, molecular, and functional aspects with vertebrate MG [ 43 ].…”

Section: Alternative Organism Models For Retina Neuroregenerationmentioning

confidence: 99%

Regenerative Strategies for Retinal Neurons: Novel Insights in Non-Mammalian Model Organisms

Catalani

Cherubini

Quondam

et al. 2022

IJMS

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A detailed knowledge of the status of the retina in neurodegenerative conditions is a crucial point for the development of therapeutics in retinal pathologies and to translate eye research to CNS disease. In this context, manipulating signaling pathways that lead to neuronal regeneration offers an excellent opportunity to substitute damaged cells and, thus, restore the tissue functionality. Alternative systems and methods are increasingly being considered to replace/reduce in vivo approaches in the study of retina pathophysiology. Herein, we present recent data obtained from the zebrafish (Danio rerio) and the fruit fly Drosophila melanogaster that bring promising advantages into studying and modeling, at a preclinical level, neurodegeneration and regenerative approaches in retinal diseases. Indeed, the regenerative ability of vertebrate model zebrafish is particularly appealing. In addition, the fruit fly is ideal for regenerative studies due to its high degree of conservation with vertebrates and the broad spectrum of genetic variants achievable. Furthermore, a large part of the drosophila brain is dedicated to sight, thus offering the possibility of studying common mechanisms of the visual system and the brain at once. The knowledge acquired from these alternative models may help to investigate specific well-conserved factors of interest in human neuroregeneration after injuries or during pathologies.

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“…Finally, relevant genes and pathways are largely conserved, and many important mammalian neuronal CSSPs have orthologs, or were even originally discovered, in Drosophila . Furthermore, neurodevelopmental processes, such as the molecular mechanisms of axon guidance and target selection, as well as neural organizational principles, such as the logical flow in the olfactory system, show striking similarity between flies and mammals ( Komiyama and Luo, 2006 ; Reichert, 2009 ; Gonda et al, 2020 ; Li F. et al, 2020 ; Malin and Desplan, 2021 ). Thus, insights and principles obtained in Drosophila are likely to be relevant to similar processes in higher organisms.…”

Section: Introductionmentioning

confidence: 99%

Spatiotemporal Control of Neuronal Remodeling by Cell Adhesion Molecules: Insights From Drosophila

Meltzer

Schuldiner

2022

Front. Neurosci.

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Developmental neuronal remodeling is required for shaping the precise connectivity of the mature nervous system. Remodeling involves pruning of exuberant neural connections, often followed by regrowth of adult-specific ones, as a strategy to refine neural circuits. Errors in remodeling are associated with neurodevelopmental disorders such as schizophrenia and autism. Despite its fundamental nature, our understanding of the mechanisms governing neuronal remodeling is far from complete. Specifically, how precise spatiotemporal control of remodeling and rewiring is achieved is largely unknown. In recent years, cell adhesion molecules (CAMs), and other cell surface and secreted proteins of various families, have been implicated in processes of neurite pruning and wiring specificity during circuit reassembly. Here, we review some of the known as well as speculated roles of CAMs in these processes, highlighting recent advances in uncovering spatiotemporal aspects of regulation. Our focus is on the fruit fly Drosophila, which is emerging as a powerful model in the field, due to the extensive, well-characterized and stereotypic remodeling events occurring throughout its nervous system during metamorphosis, combined with the wide and constantly growing toolkit to identify CAM binding and resulting cellular interactions in vivo. We believe that its many advantages pose Drosophila as a leading candidate for future breakthroughs in the field of neuronal remodeling in general, and spatiotemporal control by CAMs specifically.

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Neural specification, targeting, and circuit formation during visual system assembly

Cited by 21 publications

References 199 publications

Retina organoids: Window into the biophysics of neuronal systems

Retina organoids: Window into the biophysics of neuronal systems

Regenerative Strategies for Retinal Neurons: Novel Insights in Non-Mammalian Model Organisms

Spatiotemporal Control of Neuronal Remodeling by Cell Adhesion Molecules: Insights From Drosophila

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