Canonical Wnt signaling exerts bidirectional control on choroid plexus epithelial development
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE162784 | GEO | 2021/11/01
REPOSITORIES: GEO
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2007-04-04 | GSE7430 | GEO
Project description:Beta-catenin is an essential mediator of canonical Wnt signaling and a central component of the cadherin-catenin epithelial adhesion complex. Dysregulation of beta-catenin expression has been described in pancreatic neoplasia. Newly published studies have suggested that beta-catenin is critical for normal pancreatic development although these reports reached somewhat different conclusions. In addition, the molecular mechanisms by which loss of beta-catenin affects pancreas development are not well understood. The goals of this study then were; 1] to further investigate the role of beta-catenin in pancreatic development using a conditional knockout approach and 2] to identify possible mechanisms by which loss of beta-catenin disrupts pancreatic development. A Pdx1-cre mouse line was used to delete a floxed beta-catenin allele specifically in the developing pancreas, and embryonic pancreata were studied by immunohistochemistry and microarray analysis. Experiment Overall Design: Parameter: embryonic pancreas from wild type and Pdx1Cre/+; beta-cateninflox/flox Experiment Overall Design: Sample type: RNA Experiment Overall Design: Source name: Embryonic day 14.6 and 16.5 pancreas Experiment Overall Design: Organism: Mus Musculus Experiment Overall Design: Strain: Derived from an intercross of Pdx1Cre/+ ; beta-cateninflox/+ mice. Experiment Overall Design: Extracted molecule:Total RNA Experiment Overall Design: In the study, we hybridized RNA from Embryonic day 14.6 and 16.5 pancreas of wild type (WT) control and Pdx1Cre/+; beta-cateninflox/flox beta-catenin null in the pancreas) embryonic pancreas to Affymetrix MOE430 2.0 GeneChip® arrays containing 45,101 well characterized mouse genes/ESTs.
2007-12-13 | E-GEOD-7430 | biostudies-arrayexpress
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Project description:Lee2003 - Roles of APC and Axin in Wnt
Pathway (without regulatory loop)
This model is described in the article:
The roles of APC and Axin
derived from experimental and theoretical analysis of the Wnt
pathway.
Lee E, Salic A, Krüger R,
Heinrich R, Kirschner MW.
PLoS Biol. 2003 Oct; 1(1): E10
Abstract:
Wnt signaling plays an important role in both oncogenesis
and development. Activation of the Wnt pathway results in
stabilization of the transcriptional coactivator beta-catenin.
Recent studies have demonstrated that axin, which coordinates
beta-catenin degradation, is itself degraded. Although the key
molecules required for transducing a Wnt signal have been
identified, a quantitative understanding of this pathway has
been lacking. We have developed a mathematical model for the
canonical Wnt pathway that describes the interactions among the
core components: Wnt, Frizzled, Dishevelled, GSK3beta, APC,
axin, beta-catenin, and TCF. Using a system of differential
equations, the model incorporates the kinetics of
protein-protein interactions, protein synthesis/degradation,
and phosphorylation/dephosphorylation. We initially defined a
reference state of kinetic, thermodynamic, and flux data from
experiments using Xenopus extracts. Predictions based on the
analysis of the reference state were used iteratively to
develop a more refined model from which we analyzed the effects
of prolonged and transient Wnt stimulation on beta-catenin and
axin turnover. We predict several unusual features of the Wnt
pathway, some of which we tested experimentally. An insight
from our model, which we confirmed experimentally, is that the
two scaffold proteins axin and APC promote the formation of
degradation complexes in very different ways. We can also
explain the importance of axin degradation in amplifying and
sharpening the Wnt signal, and we show that the dependence of
axin degradation on APC is an essential part of an
unappreciated regulatory loop that prevents the accumulation of
beta-catenin at decreased APC concentrations. By applying
control analysis to our mathematical model, we demonstrate the
modular design, sensitivity, and robustness of the Wnt pathway
and derive an explicit expression for tumor suppression and
oncogenicity.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000658.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2018-03-20 | BIOMD0000000658 | BioModels
Project description:The Wnt/β-catenin signalling pathway is a key regulator of embryonic stem cell self-renewal and differentiation. Constitutive activation of this pathway has been shown to significantly increase mouse embryonic stem cell (mESC) self-renewal and pluripotency marker expression. In this study, we generated a novel β-catenin knock-out model in mESCs by using CRISPR/Cas9 technology to delete putatively functional N-terminally truncated isoforms observed in previous knock-out models. While we showed that aberrant N-terminally truncated isoforms are not functional in mESCS, we observed that canonical Wnt signalling is not active in mESCs, as β-catenin ablation does not alter mESC transcriptional profile in LIF-enriched culture conditions; on the other hand, Wnt signalling activation represses mESC spontaneous differentiation. We also showed that transcriptionally silent β-catenin (ΔC) isoforms can rescue β-catenin knock-out self-renewal defects in mESCs, cooperating with TCF1 and LEF1 in the inhibition of mESC spontaneous differentiation in a Gsk3 dependent manner.
2020-01-10 | GSE143340 | GEO
Project description:During canonical Wnt signalling the activity of nuclear beta-catenin is largely mediated by the TCF/LEF family of transcription factors. To challenge this view we used the CRISPR/Cas9 genome editing approach to generate HEK 293T cell clones simultaneously carrying loss-of-function alleles of all four TCF/LEF genes. Exploiting unbiased whole transcriptome sequencing studies, we found that a subset of beta-catenin transcriptional targets did not require TCF/LEF factors for their regulation. Consistent with this finding, we observed in a genome-wide analysis that beta-catenin occupied specific genomic regions in the absence of TCF/LEF. Finally, we revealed the existence of a transcriptional activity of beta-catenin that specifically appears when TCF/LEF factors are absent, and refer to this as beta-catenin-GHOST response. Collectively, this study uncovers a previously neglected modus operandi of beta-catenin that bypasses the TCF/LEF transcription factors.
2018-11-22 | E-MTAB-7028 | biostudies-arrayexpress