Photoreceptor Otx2 cKO
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE138097 | GEO | 2019/09/28
REPOSITORIES: GEO
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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: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:In the mature mouse retina, Otx2 is expressed in both retinal pigmented epithelium (RPE) and photoreceptor (PR) cells, and Otx2 knock-out (KO) in the RPE alone results in PR degeneration. To study the cell-autonomous function of OTX2 in PRs, we performed PR-specific Otx2 KO (cKO) in adults. As expected, the protein disappears completely from PR nuclei but is still observed in PR inner and outer segments while its level concomitantly decreases in the RPE, suggesting a transfer of OTX2 from RPE to PRs in response to Otx2 ablation in PRs. The ability of OTX2 to transfer from RPE to PRs was verified by viral expression of tagged-OTX2 in the RPE. Transferred OTX2 distributed across the PR cytoplasm, suggesting functions distinct from nuclear transcription regulation. PR-specific Otx2 cKO did not alter the structure of the retina but impaired the translocation of PR arrestin-1 on illumination changes, making mice photophobic. RNA-seq analyses following Otx2 KO revealed downregulation of genes involved in the cytoskeleton that might account for the arrestin-1 translocation defect, and of genes involved in extracellular matrix (ECM) and signaling factors that may participate in the enhanced transfer of OTX2. Interestingly, several RPE-specific OTX2 target genes involved in melanogenesis were downregulated, lending weight to a decrease of OTX2 levels in the RPE following PR-specific Otx2 cKO. Our study reveals a new role of endogenous OTX2 in PR light adaptation and demonstrates the existence of OTX2 transfer from RPE to PR cells, which is increased on PR-specific Otx2 ablation and might participate in PR neuroprotection.
| S-EPMC8496205 | biostudies-literature
Project description:A better understanding of how Otx2 regulates plasticity in the visual cortex requires that its non-cell autonomous transcription targets be identified. We dissected layer IV of the visual cortex and used RNA-sequencing to analyze gene expression at postnatal day 30 (P30) and P100 in wild-type (WT) and Otx2+/GFP heterozygotes mice. The rationale is that CP plasticity is opened at P30 in WT but not in Otx2+/GFP mice, given that genetic deletion delays CP opening (Sugiyama et al., 2008), and that the CP is closed at P100 in WT mice and not yet in Otx2+/GFP mice. Thus, genes with similar expression at P30 in Otx2+/GFP and at P100 in WT mice but with a different level of expression during the critical period (P30 in WT or P100 Otx2+/GFP mice) were considered as potential genes involved in plasticity.
2018-04-19 | GSE98258 | GEO
Project description:To analyze OTX2 function in adult choroid plexus, we performed several OTX2 co-immunoprecipitation (co-IP) experiments with mass spectrometry analysis to identify potential protein partners. We previously discovered that OTX2 protein also accumulates non-cell autonomously in subventricular zone (SVZ) and rostral migratory stream (RMS) astrocytes and in visual cortex (VCx) parvalbumin cells. The identification of alternate protein partners in cell-autonomous and non-cell-autonomous contexts would suggest OTX2 takes on specific roles after transferring between cells. In order to test this hypothesis, and to reinforce choroid plexus analysis, we also performed OTX2 co-IP on lysates from adult mouse SVZ, RMS and VCx.
2021-08-23 | PXD021244 | Pride
Project description:Development of the vertebrate eye, like many developmental systems, depends on genes that are used iteratively in multiple distinct processes. The OTX2 transcription factor is one such gene, with a requirement for eye formation, photoreceptor and retinal pigment epithelium specification, among others. During the time period of retinal fate choice, OTX2 is expressed in subsets of retinal progenitor cells with restricted fate choices. However, given the multiple roles for OTX2 and limitations of conventional conditional knockout strategies, the functional significance of its expression is unknown. The present study reports the use of CRISPR/Cas9 gene editing to produce somatic mutations of OTX2 in the chick retina, and identifies similar phenotypes to those observed in human patients. In addition, single cell RNA sequencing was used to determine the functional consequences of OTX2 gene editing by CRISPR/Cas9 on the population of cells derived from OTX2-expressing retinal progenitor cells. This not only confirms that OTX2 is required for the generation of photoreceptors, but also for maintaining the proliferative potential of cells and suppressing the formation of specific retinal fates. These include specific subtypes of retinal ganglion and horizontal cells, suggesting that in this context OTX2 functions to repress sister cell fate choices. Upregulation of key transcription factors involved in the formation of these cells was observed suggesting that OTX2 is upstream of critical nodes of gene regulatory networks of these alternative fates.
2020-03-01 | GSE142244 | GEO
Project description:To analyze the expression profile in the Otx2 knock-in (a knock-in mouse line expressing Otx2 from the Crx locus on chromosome 7) and Crx knockout retina, we performed a microarray analysis using wild-type (Crx +/+), Otx2 KI (Crx Otx2/Otx2) and Crx KO (Crx -/-) retina at P12.
2020-01-24 | GSE129443 | GEO
Project description:In this study, we demonstrated that OTX2 was transcriptionally and post-transcriptionally regulated by O-GlcNAcylation. We describe the modes of degradation of this essential homeobox protein involving both the proteasome and macroautophagy. While the proteasome remains the canonical degradation pathway, we demonstrated that OTX2 forms oligomers and/or aggregates that are resistant to proteasomal degradation and require macroautophagy. Furthermore, elevated cellular concentration of OTX2 promoted aggregation, OTX2 could either interact with the chaperonin CCT5 or be O-GlcNAcylated at the key residues (S1135/S136/T137) to prevent its oligomerization, suggesting a protective role of O-GlcNAcylation in OTX2 turnover.
2024-01-22 | PXD040353 | Pride
Project description:The choroid plexuses (ChPs) are the main regulators of cerebrospinal fluid (CSF) composition and thereby also control the composition of a principal source of signaling molecules that is in direct contact with neural stem cells in the developing brain. The regulators of ChP development mediating the acquisition of a fate that differs from the neighboring neuroepithelial cells are poorly understood. Here, we demonstrate in mice a crucial role for the transcription factor Otx2 in the development and maintenance of ChP cells. Deletion of Otx2 by the Otx2-CreERT2 driver line at E9 resulted in a lack of all ChPs, whereas deletion by the Gdf7-Cre driver line affected predominately the hindbrain ChP, which was reduced in size, primarily owing to an increase in apoptosis upon Otx2 deletion. Strikingly, Otx2 was still required for the maintenance of hindbrain ChP cells at later stages when Otx2 deletion was induced at E15, demonstrating a central role of Otx2 in ChP development and maintenance. Moreover, the predominant defects in the hindbrain ChP mediated by Gdf7-Cre deletion of Otx2 revealed its key role in regulating early CSF composition, which was altered in protein content, including the levels of Wnt4 and the Wnt modulator Tgm2. Accordingly, proliferation and Wnt signaling levels were increased in the distant cerebral cortex, suggesting a role of the hindbrain ChP in regulating CSF composition, including key signaling molecules. Thus, Otx2 acts as a master regulator of ChP development, thereby influencing one of the principal sources of signaling in the developing brain, the CSF. We performed gene expression microarray analysis of fourth ventricular choroid plexus tissue from Otx2 k.o. mice compared to wildtype mice from the same litters.
2013-02-05 | E-GEOD-27630 | biostudies-arrayexpress