Ikaros family proteins redundantly regulate temporal patterning in the developing mouse retina

Javed, Amit; Santos-França, Pedro L.; Mattar, Pierre; Cui, Allie; Kassem, Fatima; Cayouette, Michel

doi:10.1242/dev.200436

Cited by 13 publications

(4 citation statements)

References 107 publications

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“…However, under ironmediated stress conditions or exposure to high concentrations for prolonged periods of time, Lcn2 may increase cell death in neurons and astrocytes [59,60]. Ikzf4 together with Ikzf1 have been identified as neuronal reprogramming factors, having been shown to reprogram fibroblasts into induced neurons and convert uninjured retinal into neuronlike cells [67,68]. The glycoprotein Chi3l1 is predominantly expressed by astrocytes.…”

Section: Discussionmentioning

confidence: 99%

Spatial transcriptomics at the brain-electrode interface in rat motor cortex and the relationship to recording quality

Whitsitt,

Saxena,

Patel

et al. 2024

J. Neural Eng.

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Study of the foreign body reaction to implanted electrodes in the brain is an important area of research for the future development of neuroprostheses and experimental electrophysiology. After electrode implantation in the brain, microglial activation, reactive astrogliosis, and neuronal cell death create an environment immediately surrounding the electrode that is significantly altered from its homeostatic state. To uncover physiological changes potentially affecting device function and longevity, spatial transcriptomics was implemented to identify changes in gene expression driven by electrode implantation and compare this differential gene expression to traditional metrics of glial reactivity, neuronal loss, and electrophysiological recording quality. For these experiments, rats were chronically implanted with functional Michigan-style microelectrode arrays, from which electrophysiological recordings (multi-unit activity, local field potential) were taken over a six-week time course. Brain tissue cryosections surrounding each electrode were then mounted for spatial transcriptomics processing. The tissue was immunolabeled for neurons and astrocytes, which provided both a spatial reference for spatial transcriptomics and a quantitative measure of glial fibrillary acidic protein (GFAP) and neuronal nuclei (NeuN) immunolabeling surrounding each implant. Results from rat motor cortex within 300µm of the implanted electrodes at 24 hours, 1 week, and 6 weeks post-implantation showed up to 553 significantly differentially expressed (DE) genes between implanted and non-implanted tissue sections. Regression on the significant DE genes identified the 6-7 genes that had the strongest relationship to histological and electrophysiological metrics, revealing potential candidate biomarkers of recording quality and the tissue response to implanted electrodes

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Section: Discussionmentioning

confidence: 99%

Spatial transcriptomics at the brain-electrode interface in rat motor cortex and the relationship to recording quality

Whitsitt,

Saxena,

Patel

et al. 2024

J. Neural Eng.

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“…The study reported that the miR-128 expression was significantly lower in patients with Ikzf1 deletion than those without Ikzf1 deletion in B-cell precursor acute lymphoblastic leukemia ( Krzanowski et al, 2017 ). Importantly, these hub genes not only participate in immune regulation but also play important roles in neurodegenerative diseases through the ceRNA network regulation ( Javed et al, 2023 ; Yi et al, 2023 ). Qin et al (2023) revealed that miR-6734-3p and its target mRNA Cyth4 expression were correlated with patients’ age in Alzheimer’s disease.…”

Section: Discussionmentioning

confidence: 99%

Analysis of shared ceRNA networks and related-hub genes in rats with primary and secondary photoreceptor degeneration

Liang,

Fang,

Yao

et al. 2023

Front. Neurosci.

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IntroductionPhotoreceptor degenerative diseases are characterized by the progressive death of photoreceptor cells, resulting in irreversible visual impairment. However, the role of competing endogenous RNA (ceRNA) in photoreceptor degeneration is unclear. We aimed to explore the shared ceRNA regulation network and potential molecular mechanisms between primary and secondary photoreceptor degenerations.MethodsWe established animal models for both types of photoreceptor degenerations and conducted retina RNA sequencing to identify shared differentially expressed long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs). Using ceRNA regulatory principles, we constructed a shared ceRNA network and performed function enrichment and protein–protein interaction (PPI) analyses to identify hub genes and key pathways. Immune cell infiltration and drug–gene interaction analyses were conducted, and hub gene expression was validated by quantitative real-time polymerase chain reaction (qRT-PCR).ResultsWe identified 37 shared differentially expressed lncRNAs, 34 miRNAs, and 247 mRNAs and constructed a ceRNA network consisting of 3 lncRNAs, 5 miRNAs, and 109 mRNAs. Furthermore, we examined 109 common differentially expressed genes (DEGs) through functional annotation, PPI analysis, and regulatory network analysis. We discovered that these diseases shared the complement and coagulation cascades pathway. Eight hub genes were identified and enriched in the immune system process. Immune infiltration analysis revealed increased T cells and decreased B cells in both photoreceptor degenerations. The expression of hub genes was closely associated with the quantities of immune cell types. Additionally, we identified 7 immune therapeutical drugs that target the hub genes.DiscussionOur findings provide new insights and directions for understanding the common mechanisms underlying the development of photoreceptor degeneration. The hub genes and related ceRNA networks we identified may offer new perspectives for elucidating the mechanisms and hold promise for the development of innovative treatment strategies.

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“…However, the percentage of Nr2e3+Crx+ cells was identical (S6Q Fig) . Therefore, the loss of cones in Hes1 mutants cannot be attributed to accelerated rod genesis. Another explanation is that Hes1 provides temporal restriction to the Otx2 lineage to prevent prenatal bipolar neuron formation [100]. Alternatively, RGC development may accelerate in the absence of Hes1, depleting the availability of transitional RPCs to activate Otx2 and adopt a cone fate.…”

Section: Plos Geneticsmentioning

confidence: 99%

Notch pathway mutants do not equivalently perturb mouse embryonic retinal development

Bosze,

Suarez-Navarro,

Cajias

et al. 2023

PLoS Genet

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In the vertebrate eye, Notch ligands, receptors, and ternary complex components determine the destiny of retinal progenitor cells in part by regulating Hes effector gene activity. There are multiple paralogues for nearly every node in this pathway, which results in numerous instances of redundancy and compensation during development. To dissect such complexity at the earliest stages of eye development, we used seven germline or conditional mutant mice and two spatiotemporally distinct Cre drivers. We perturbed the Notch ternary complex and multiple Hes genes to understand if Notch regulates optic stalk/nerve head development; and to test intracellular pathway components for their Notch-dependent versus -independent roles during retinal ganglion cell and cone photoreceptor competence and fate acquisition. We confirmed that disrupting Notch signaling universally blocks progenitor cell growth, but delineated specific pathway components that can act independently, such as sustained Hes1 expression in the optic stalk/nerve head. In retinal progenitor cells, we found that among the genes tested, they do not uniformly suppress retinal ganglion cell or cone differentiation; which is not due differences in developmental timing. We discovered that shifts in the earliest cell fates correlate with expression changes for the early photoreceptor factor Otx2, but not with Atoh7, a factor required for retinal ganglion cell formation. During photoreceptor genesis we also better defined multiple and simultaneous activities for Rbpj and Hes1 and identify redundant activities that occur downstream of Notch. Given its unique roles at the retina-optic stalk boundary and cone photoreceptor genesis, our data suggest Hes1 as a hub where Notch-dependent and -independent inputs converge.

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Ikaros family proteins redundantly regulate temporal patterning in the developing mouse retina

Cited by 13 publications

References 107 publications

Spatial transcriptomics at the brain-electrode interface in rat motor cortex and the relationship to recording quality

Spatial transcriptomics at the brain-electrode interface in rat motor cortex and the relationship to recording quality

Analysis of shared ceRNA networks and related-hub genes in rats with primary and secondary photoreceptor degeneration

Notch pathway mutants do not equivalently perturb mouse embryonic retinal development

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