<i>Frizzled3</i>Shapes the Development of Retinal Rod Bipolar Cells

Shen, Ni; Qu, Yibo; Yu, Yankun; So, Kwok-Fai; Goffinet, André M.; Vardi, Noga; Xu, Ying; Zhou, Libing

doi:10.1167/iovs.16-19281

Cited by 8 publications

(3 citation statements)

References 40 publications

(45 reference statements)

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“…4E). In wild-type mice, by P14 rBCs have achieved their mature morphology, with apical dendrites contacting the OPL (Elshatory et al, 2007;Shen et al, 2016). Compared with the complex dendritic arbors of the cells located at the top of the INL, the displaced rBCs exhibit simpler shorter dendritic protrusions that often appear to be incorrectly polarized (arrows in Fig.…”

Section: Rbx2 Deficiency Leads To Layering Defects In the Retina In Amentioning

confidence: 99%

RBX2 maintains final retinal cell position in a DAB1-dependent and -independent fashion

et al. 2018

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The laminated structure of the retina is fundamental for the organization of the synaptic circuitry that translates light input into patterns of action potentials. However, the molecular mechanisms underlying cell migration and layering of the retina are poorly understood. Here, we show that RBX2, a core component of the E3 ubiquitin ligase CRL5, is essential for retinal layering and function. RBX2 regulates the final cell position of rod bipolar cells, cone photoreceptors and Muller glia. Our data indicate that sustained RELN/DAB1 signaling, triggered by depletion of RBX2 or SOCS7 - a CRL5 substrate adaptor known to recruit DAB1 - causes rod bipolar cell misposition. Moreover, whereas SOCS7 also controls Muller glia cell lamination, it is not responsible for cone photoreceptor positioning, suggesting that RBX2, most likely through CRL5 activity, controls other signaling pathways required for proper cone localization. Furthermore, RBX2 depletion reduces the number of ribbon synapses and disrupts cone photoreceptor function. Together, these results uncover RBX2 as a crucial molecular regulator of retina morphogenesis and cone photoreceptor function.

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Section: Rbx2 Deficiency Leads To Layering Defects In the Retina In Amentioning

confidence: 99%

RBX2 maintains final retinal cell position in a DAB1-dependent and -independent fashion

et al. 2018

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“…For example, interaction between pikachurin in the synaptic cleft and dystroglycan (DG) on rod axon terminals is necessary for the invagination of RBC dendrites into rod spherules (Kanagawa et al 2010, Omori et al 2012, Sato et al 2008. RBC dendritic invagination also requires the presence of extracellular leucine-rich repeat and fibronectin type III domain containing 1 (ELFN1) (Cao et al 2015), an adhesion molecule expressed by rods that binds mGluR6, the voltage-gated calcium channel Ca v 1.4 (Zabouri & Haverkamp 2013), and the planar cell polarity transmembrane receptor Frizzled3 (Shen et al 2016). In mice lacking Sema6A or PlexA4, rod spherules form synapses but do not exhibit the triad arrangement because only one HC process, instead of two, invaginates the spherule (Matsuoka et al 2012).…”

Section: Development Of Rod Pathway Circuitsmentioning

confidence: 99%

Establishing Wiring Specificity in Visual System Circuits: From the Retina to the Brain

Zhang

Kolodkin

Wong

et al. 2017

Annu. Rev. Neurosci.

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The retina is a tremendously complex image processor, containing numerous cell types that form microcircuits encoding different aspects of the visual scene. Each microcircuit exhibits a distinct pattern of synaptic connectivity. The developmental mechanisms responsible for this patterning are just beginning to be revealed. Furthermore, signals processed by different retinal circuits are relayed to specific, often distinct, brain regions. Thus, much work has focused on understanding the mechanisms that wire retinal axonal projections to their appropriate central targets. Here, we highlight recently discovered cellular and molecular mechanisms that together shape stereotypic wiring patterns along the visual pathway, from within the retina to the brain. Although some mechanisms are common across circuits, others play unconventional and circuit-specific roles. Indeed, the highly organized connectivity of the visual system has greatly facilitated the discovery of novel mechanisms that establish precise synaptic connections within the nervous system.

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“…As expected, we observe receptor expression patterns in pseudotime that we cannot confirm with the heterogeneity present in the canonical time points. For instance, receptors like FZD3 and IGF1R are mostly related to early retinal differentiation ( 26, 27 ), but this is only apparent in pseudotime with their highest expression in the t 1 -t 3 state ( Figure 2E ).…”

Section: Resultsmentioning

confidence: 99%

Sustained neurotrophic factor cotreatment enhances donor and host retinal ganglion cell survival in mice

Soucy,

Kriukov,

Oswald

et al. 2024

Preprint

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Retinal ganglion cells (RGCs) lack regenerative capacity in mammals, and their degeneration in glaucoma leads to irreversible blindness. Traditional RGC transplantation has been limited by poor survival rates of transplanted cells in the hostile microenvironment of a diseased retina. Our research identifies brain-derived neurotrophic factor (BDNF) and glial-derived neurotrophic factor (GDNF) as key elements in retinal development and RGC survival through in silico analysis of the single-cell transcriptome of developing human retinas. Although these factors are abundant during development, they diminish in adulthood. Here, we demonstrate that a slow-release formulation of BDNF and GDNF enhances RGC differentiation and survival in vitro and improves RGC transplantation outcomes in mouse models. This co-treatment increased survival and coverage of donor RGCs within the retina and enhanced neurite extension toward the optic nerve head. Lastly, this co-treatment showed neuroprotective effects on host RGCs, preserving retinal function in a model of optic neuropathy. Altogether, our findings suggest that manipulating the retinal microenvironment with slow-release neurotrophic factors holds promise in regenerative medicine for treating glaucoma and other optic neuropathies. This approach not only improves donor cell survival and integration but also provides a neuroprotective benefit to host cells, indicating a significant advancement for glaucoma therapies.

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Frizzled3Shapes the Development of Retinal Rod Bipolar Cells

Abstract: Frizzled3 is required to shape the pattern of RBC somas and dendrites, and the structural and functional connectivity between rods and RBCs. Our results highlight novel functions for Fzd3 in regulating retinal development.

Cited by 8 publications

References 40 publications

RBX2 maintains final retinal cell position in a DAB1-dependent and -independent fashion

RBX2 maintains final retinal cell position in a DAB1-dependent and -independent fashion

Establishing Wiring Specificity in Visual System Circuits: From the Retina to the Brain

Sustained neurotrophic factor cotreatment enhances donor and host retinal ganglion cell survival in mice

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