Unifying Developmental Programs for Embryonic and Post-Embryonic Neurogenesis in the Zebrafish Retina
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ABSTRACT:
ORGANISM(S): Danio rerio
PROVIDER: GSE122680 | GEO | 2020/05/19
REPOSITORIES: GEO
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Project description:Unifying Developmental Programs for Embryonic and Post-Embryonic Neurogenesis in the Zebrafish Retina
| PRJNA506002 | ENA
Project description:To expedite gene discovery in eye development and its associated defects, we previously developed a bioinformatics resource-tool iSyTE (integrated Systems Tool for Eye gene discovery). However, iSyTE is presently limited to lens tissue and is predominantly based on transcriptomics datasets. Therefore, to extend the iSyTE approach to retina development on the proteome level, we performed high-throughput tandem mass spectrometry (MS/MS) on mouse embryonic day (E)14.5 retina and identified an average of 3,300 proteins per sample (n=5). High-throughput expression profiling-based gene discovery approaches–involving either transcriptomics or proteomics–pose a key challenge of prioritizing select candidates from thousands of RNA/proteins expressed in a particular cell/tissue type. To address this, we used MS/MS proteome data from mouse whole embryonic body (WB) as a reference dataset and performed comparative analysis–termed “in silico WB-subtraction”–with the retina proteome dataset. In silico WB-subtraction identified 90 high-priority proteins with retina-enriched expression at stringency criteria of 2.5 average spectral counts, 2.0 fold-enrichment, False Discovery Rate <0.01. These top candidates represent a pool of retina-enriched proteins, several of which are associated with retinal biology and/or defects (e.g., Aldh1a1, Ank2, Ank3, Dcn, Dync2h1, Egfr, Ephb2, Fbln5, Fbn2, Hras, Igf2bp1, Msi1, Rbp1, Rlbp1, Tenm3, Yap1, etc.), indicating the effectiveness of this approach. Importantly, in silico WB-subtraction also identified several new high-priority candidates with potential regulatory function in retina development. Finally, proteins exhibiting expression or enriched-expression in the retina are made accessible in a user-friendly manner at iSyTE (https://research.bioinformatics.udel.edu/iSyTE/), to allow effective visualization of this information by the research community to facilitate eye gene discovery.
2023-10-09 | PXD039490 | Pride
Project description:In the vertebrate retina, the Otx2 transcription factor plays a crucial role in the cell fate determination of both rod and cone photoreceptors. Otx2 conditional knockout (CKO) mice exhibited a total absence of rods and cones in the retina due to their cell fate conversion to amacrine-like cells. In order to investigate the entire transcriptome regulated by Otx2 in the developing retina, we performed microarray analysis on the Otx2 CKO retina. In order to clarify the molecular role of Otx2 in transcriptional regulation during development, we investigated the expression profile of the Otx2 CKO retina compared with that of the control retina with the genotype Otx2flox/flox;Crx-cre- using microarrays at two time points, P1 and P12.
2011-05-18 | E-GEOD-21900 | biostudies-arrayexpress
Project description:The relative contribution of extrinsic and intrinsic mechanisms to cortical development is an intensely debated issue and an outstanding question in neurobiology. Currently, the emerging view is that interplay between intrinsic genetic mechanisms and extrinsic information shape different stages of cortical development. Yet, whereas the intrinsic program of early neocortical developmental events has been at least in part decoded, the exact nature and impact of extrinsic signaling are still elusive and controversial. We found that in the mouse developing visual system, acute pharmacological inhibition of spontaneous retinal activity (retinal waves-RWs) during embryonic stages increase the rate of corticogenesis (cell cycle withdrawal). Furthermore, early perturbation of retinal spontaneous activity leads to changes of cortical layer structure at a later time point. These data suggest that mouse embryonic retina delivers long-distance information capable of modulating cell genesis in the developing visual cortex and that spontaneous activity is the candidate long-distance acting extrinsic cue mediating this process. In addition, these data may support spontaneous activity to be a general signal coordinating neurogenesis in other developing sensory pathways or areas of the central nervous system.
| S-EPMC2999540 | biostudies-other
Project description:The microarray analysis was designed to test the effects of HES5.3 siRNAs, Atoh7 siRNAs and nt siRNAs on gene expression in embryonic chick retina.
2013-03-01 | E-MTAB-1430 | biostudies-arrayexpress
Project description:In the vertebrate retina, the Otx2 transcription factor plays a crucial role in the cell fate determination of both rod and cone photoreceptors. Otx2 conditional knockout (CKO) mice exhibited a total absence of rods and cones in the retina due to their cell fate conversion to amacrine-like cells. In order to investigate the entire transcriptome regulated by Otx2 in the developing retina, we performed microarray analysis on the Otx2 CKO retina.
2011-05-18 | GSE21900 | GEO
Project description:To identify epigenetic programs underlying differentiation of mouse retina, we performed ATAC-Seq on bulk native retina (NaR) and iPSC-derived 3D retinal aggregates (3D-RA) at three matched stages of development: embryonic day (E)13 vs differentiation day (DD)13, postnatal day (P)0 vs DD21, and P5 vs DD25. We produced a total of 24 ATAC-seq libraries with two technical replicates (using either 1 ul or 2 ul of TDE1 enzyme) of two biological replicates, and two genomic DNA libraries to use for background controls.
2021-06-30 | E-MTAB-9440 | biostudies-arrayexpress
Project description:In mammals, loss of retinal cells due to disease or trauma is an irreversible process which can lead to blindness. Interestingly, regeneration of retinal neurons is a well-established process in some non-mammalian vertebrates and is driven by the Muller glia (MG), which are able to re-enter the cell cycle and reprogram into neurogenic progenitors upon retinal injury or disease. Progress has been made to restore this mechanism in mammals to promote retinal regeneration: MG can be stimulated to generate new neurons in vivo in the adult mouse retina after the over-expression of the pro-neural transcription factor Ascl1. In this study, we applied the same strategy to reprogram human MG derived from fetal retina and retinal organoids into neurons. Combining scRNA-seq, scATAC-seq, Immunofluorescence, and electrophysiology we demonstrate that human MG can be reprogrammed into neurogenic cells in vitro.
2023-10-30 | GSE246169 | GEO
Project description:The histone methyltransferase complex PRC2 controls key steps in developmental transitions and cell fate choices. However, its roles in vertebrate eye development remain unknown. Here we report that in Xenopus PRC2 regulates the progression of retinal progenitors from proliferation to differentiation. We show that the PRC2 core components are enriched in retinal progenitors and downregulated with differentiation. Knockdown of the PRC2 core component Ezh2 leads to reduced retinal progenitor proliferation in part due to upregulation of the cdk inhibitor p15Ink4b. In addition, while PRC2 knockdown does not alter eye patterning, retinal progenitor gene expression or expression of the neural competence factor Sox2, it does cause suppression of proneural bHLH gene expression, indicating that PRC2 is critical for the initiation of neural differentiation in the retina. Consistent with this, knocking down or blocking PRC2 function constrains the generation of most retinal neural cell types and promotes a Mueller glial cell fate decision. We also show that Wnt/?-catenin signaling acting through the receptor Frizzled 5, but independent of Sox2, regulates expression of key PRC2 subunits in the developing retina. This is consistent with a role for this pathway in coordinating proliferation and the transition to neurogenesis in the Xenopus retina. Our data establishes PRC2 as a regulator of proliferation and differentiation during eye development. Xenopus embryos were injected at the 8-cell stage with 5ng Ezh2 ATG MO or 5ng control MO (scrambled sequence of Ezh2 ATG MO) together with 400 pg mRNA for GFP as a lineage tracer. At stage 27, GFP-positive eyes were isolated by microdissection. Pools of 20-25 eyes were used to prepare total RNA for each sample on the microarray. 4 control and 4 Ezh2 ATG MO samples were hybridized to Agilent 1-color microarrays.
2013-05-30 | E-GEOD-47456 | biostudies-arrayexpress
Project description:Gene regulatory networks (GRNs), consisting of transcription factors and their target cis-regulatory sequences, control neurogenesis and cell fate specification in the developing central nervous system, but their organization is poorly characterized. In this study, we performed integrated scRNA-seq and scATAC-seq analysis from both mouse and human retina to profile dynamic changes in gene expression, chromatin accessibility and transcription factor footprinting during retinal neurogenesis and gliogenesis. We identified multiple interconnected, evolutionarily-conserved GRNs consisting of cell type-specific transcription factors that both activate expression of genes within their own network and often inhibit expression of genes in other networks. These GRNs control state transitions within primary retinal progenitors that underlie temporal patterning, regulate the transition from primary to neurogenic progenitors, and drive specification of each major retinal cell type. We confirmed the prediction of this analysis that the NFI transcription factors Nfia, Nfib, and Nfix selectively activate expression of genes that promote late-stage temporal identity in primary retinal progenitors. We also used GRNs to identify additional transcription factors that selectively promote (Insm1/2) and inhibit (Tbx3, Tcf7l1/2) rod photoreceptor specification in postnatal retina. This study provides an inventory of cis- and trans-acting factors that control retinal development, identifies transcription factors that control the temporal identity of retinal progenitors and cell fate specification, and will potentially help guide cell-based therapies aimed at replacing retinal neurons lost due to disease.
2021-08-03 | GSE181251 | GEO