Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA122803 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:This SuperSeries is composed of the following subset Series:; GSE16691: Transcriptional regulation by Norrin-Frizzled4 signaling in the embryonic yolk sac; GSE16703: Long-term effect on the transcriptome of a decrement in Norrin/Frizzled4/Lrp signaling in retinal endothelial cells; GSE16705: Transcriptional response to Frizzled4 signaling in cultured retinal endothelial cells; GSE16707: Long-term effect on the transcriptome of loss of Frizzled4 signaling in cerebellar endothelial cells Experiment Overall Design: Refer to individual Series
2009-10-10 | E-GEOD-16841 | biostudies-arrayexpress
Project description:To characterize the long-term effect on the transcriptome of a decrement in Norrin/Fz4/Lrp signaling, microarray hybridization was performed with RNA from acutely dissociated and anti-PECAM immunoaffinity-purified adult WT, Fz4-/-, Lrp5-/-, and Norrin- retinal vascular cells. Experiment Overall Design: Retinal endothelial cells from 5-10 adult mice were pooled for each sample, the cell immuno-purification procedure follows that described by Matsubara et al. (2000) and Su et al. (2003). 3 replicates of each mutant and 6 replicates of control wild type animals were analyzed.
2009-10-10 | E-GEOD-16703 | biostudies-arrayexpress
Project description:To characterize the long-term effect on the transcriptome of a decrement in Norrin/Fz4/Lrp signaling, microarray hybridization was performed with RNA from acutely dissociated and anti-PECAM immunoaffinity-purified adult WT, Fz4-/-, Lrp5-/-, and Norrin- retinal vascular cells.
2009-10-01 | GSE16703 | GEO
Project description:Canonical Wnt signaling in endothelial cells (ECs) is required for vascularization of the central nervous system (CNS) and for formation and maintenance of barrier properties unique to CNS vasculature. Gpr124 is an orphan member of the adhesion G-protein-coupled receptor family that is expressed in ECs and is essential for CNS angiogenesis and barrier formation via an unknown mechanism. Using canonical Wnt signaling assays in cell culture and genetic loss- and gain-of-function experiments in mice, we show that Gpr124 functions as a co-activator of Wnt7a- and Wnt7b-stimulated canonical Wnt signaling via a Frizzled receptor and Lrp co-receptor, and that Gpr124-stimulated signaling functions in concert with Norrin/Frizzled4 signaling to control CNS vascular development. These experiments identify Gpr124 as a ligand-specific co-activator of canonical Wnt signaling. Total mRNA from HEK-293/STF cells was subjected to RNAseq
2014-08-20 | E-GEOD-60529 | biostudies-arrayexpress
Project description:To identify genes induced by Norrin in bEnd.3 cells (mouse brain endothelial cell line), we treated the cells with recombinant Norrin. It is known that the Norrin ligand induces beta-catenin-dependent (also known as canonical) signaling through binding to a receptor complex containing Frizzled4 (FZD4). First, we confirmed that receptor complex components, FZD4, LRP5/6, and TSPAN12, were expressed in bEnd.3 cells. Next, we observed that Norrin treatment strongly induces Axin2, a beta-catenin-dependent signaling response gene. Multiple norrin-induced DEGs were identified, including P2ry1. However, it is noted that many DEGs identified in previous scRNAseq studies on retinal vascular cells in Ndp and Tspan12 KO mice are not induced in bEnd.3. cells. This observation suggests that bEnd.3 cells are a good model system for studying signal initiation and signal transduction; however, they may not capture all aspects of cellular behavior.
2026-04-11 | GSE299490 | GEO
Project description:Canonical Wnt signaling in endothelial cells (ECs) is required for vascularization of the central nervous system (CNS) and for formation and maintenance of barrier properties unique to CNS vasculature. Gpr124 is an orphan member of the adhesion G-protein-coupled receptor family that is expressed in ECs and is essential for CNS angiogenesis and barrier formation via an unknown mechanism. Using canonical Wnt signaling assays in cell culture and genetic loss- and gain-of-function experiments in mice, we show that Gpr124 functions as a co-activator of Wnt7a- and Wnt7b-stimulated canonical Wnt signaling via a Frizzled receptor and Lrp co-receptor, and that Gpr124-stimulated signaling functions in concert with Norrin/Frizzled4 signaling to control CNS vascular development. These experiments identify Gpr124 as a ligand-specific co-activator of canonical Wnt signaling.
2014-08-20 | GSE60529 | GEO
Project description:Long-term effect on the transcriptome of loss of Frizzled4 signaling in cerebellar endothelial cells
| PRJNA122687 | ENA
Project description:Using mice with targeted gene mutations, we identify (1) distinct roles for different canonical Wnt signaling components in central nervous system (CNS) vascular development and in the specification of the blood-brain and blood-retina barriers (BBB and BRB) and (2) differential sensitivities of the vasculature in various CNS regions to perturbations in canonical Wnt signaling components. We find nearly equivalent roles for Lrp5 and Lrp6 in brain vascular development and barrier maintenance but a dominant role for Lrp5 in the retinal vasculature, an especially high sensitivity of the BBB in the cerebellum and pons/interpeduncular nuclei to decrements in canonical Wnt signaling, and plasticity in the barrier properties of mature CNS vasculature. Brain and retinal vascular defects caused by loss of Norrin/Frizzled4 signaling can be fully rescued by stabilizing beta-catenin, and loss of beta-catenin’s transcriptional activation domain or expression of a dominant negative Tcf4 recapitulates the vascular development and barrier defects seen with loss of receptor, co-receptor, or ligand, indicating that Norrin/Frizzled4 signaling acts predominantly by beta-catenin-dependent transcriptional regulation. This work strongly supports a model in which identical or nearly identical canonical Wnt signaling mechanisms mediate neural tube and retinal vascularization and maintain the BBB and BRB. Total retina RNA from P10 WT, NdpKO, Ctnnb1flex3/+;Pdgfb-CreER, and NdpKO;Ctnnb1flex3/+;Pdgfb-CreER mice was subjected to RNAseq
2014-06-05 | E-GEOD-56461 | biostudies-arrayexpress
Project description:Frizzled4 (FZD4) is a pivotal receptor for Norrin and Wnt7a/b that mediates CNS angiogenesis, blood-brain barrier function and blood-retina barrier function. FZD4 is a target for pharmacological interventions in retinal and neurological disease. In order to understand mechanisms of regulation of Frizzled4 activity, two proximity biotinylation screens were performed, one in HEK293T cells and one in HeLa cells. For the screen in HEK293T cells, cells were transiently transfected. 24 hours later, cells were stimulated with 50 µM biotin for an additional 24 hours. Samples were processed and subjected to LC-MS/MSas described (PMID: 29516480). Samples S480 and S483 were biological replicates of cells co-transfected with V5-FZD4-BioID, HA-LRP5, and HA-TSPAN12 to reconstitute the norrin receptor complex. Samples S481 and S484 were biological replicates of cells co-transfected with V5-FZD4-BioID, HA-LRP5, and HA-TSPAN12 that were stimulated with flag-AP-Norrin conditioned media during the 24 hour biotin incubation period to induce norrin/frizzled4 signaling. Sample S479 and S482 were biological replicates of cells co-transfected with GFP-BioID, HA-LRP5, and HA-TSPAN12 as negative control. For the screen in HeLa cells, cells were transfected and biotinylated as described above. Sample S454 was transfected with V5-FZD4 (without BioID fusion, as a negative control). Sample S455 was transfected with GFP-BioID as another negative control. Sample S456 and S457 were transfected with V5-FZD4-BioID, of which only S457 was stimulated with flag-AP-Norrin conditioned medium during the biotin incubation period in order to induce FZD4 endocytosis. Multiple known and novel proximity interactors were identified in HEK293T and HeLa cells with high specificity. Comparisons of cells stimulated with norrin vs. vehicle indicate that proximity interactors of FZD4 were largely similar in cells with and without norrin stimulation in an overexpression context.
2026-05-15 | PXD065058 | Pride
Project description:Transcriptional response to Frizzled4 signaling in cultured retinal endothelial cells
| PRJNA122805 | ENA