Gene expression profile of embryonic retinas expressing c-hairy1, Delta-1, or Wnt2b
Ontology highlight
ABSTRACT:
ORGANISM(S): Gallus gallus
PROVIDER: GSE15382 | GEO | 2009/03/27
SECONDARY ACCESSION(S): PRJNA117115
REPOSITORIES: GEO
Similar Datasets
Project description:Expression profile of embryonic retinas expressing exogenous c-hairy1, Delta-1, or Wnt2b. These genes inhibits neuronal differentiation, and the results provide insight into the mechanism that keeps retinal progenitor cells undifferentiated. In the vertebrate retina, stem cell-like progenitor cells are maintained in a distinct region, called the ciliary marginal zone (CMZ). Canonical Wnt signaling regulates the maintenance of the progenitor cells in the CMZ. However, its downstream molecular mechanisms have remained largely unclear. Here, we show that c-hairy1, an established Notch signaling effector, mediates the Wnt-dependent maintenance of CMZ progenitor cells in chickens. Interestingly, unlike other developmental contexts where Hes gene expression is regulated by Notch signaling, the c-hairy1 expression in the CMZ is regulated by Wnt signaling. c-hairy1 is necessary and sufficient for the expression of a set of molecular markers characteristic of the CMZ, and Wnt2b fails to induce CMZ markers when c-hairy1 activity is inhibited. Furthermore, microarray analysis identifies multiple Wnt-responsive transcription factors that activate c-hairy1 expression. We thus propose that c-hairy1 functions as a node downstre am of Wnt signaling to maintain progenitor cells in the CMZ. Total RNA was purified from E6.5 retinas transfected either with c-hairy1, Wnt2b, Delta, or mock-expressing RCAS plasmid using Trizol reagent (Invitrogen). Microarray analysis using Gene Chip Chicken Genome Array (Affymetrix) was performed according to the manufacturer’s protocols. Data were analyzed using GCOS (Affymetrix) and dChip (Li and Wong, 2001). GCOS and dChip produced similar results. The data submitted is from GCOS. To explore candidates for new Wnt target genes, genes with higher expression in Wnt2b-expressing retina than control or Delta1-expressing retinas were selected for further analysis.
2009-03-27 | E-GEOD-15382 | biostudies-arrayexpress
Project description:We report the transcriptional changes associated with inhibition of recycling endosome function within the developing zebrafish retina. Recycling endosome function was inhibited through transgenic expression of a Rab11a dominant negative protein within the developing retinal progenitor cells using UAS::mCherry-Rab11aS25N; vsx2::Gal4 transgenic zebrafish. Changes in gene expression, compared to vsx2:Gal4 controls were profiled through bulk RNA-sequencing experiments of dissected zebrafish retinas. Gene expression changes resulting from inhibition of recycling endosome function were then compared to experiments in which canonical signaling pathways were modulated, including activation of Notch-signaling (over-expression of the constitutively active Notch1a intracellular domain; UAS::myc-NICD1a; vsx2::Gal4), activation of Wnt-signaling (over-expression of Wnt2b; UAS::EGFP-Wnt2b;; vsx2::Gal4), activation of Hippo-signaling (over-expression of nuclear retained YapS87A; dRED::UAS::YapS87A; vsx2::Gal4), and inhibition of mTor signaling (through treatment of zebrafish embryos with Torrin).
2021-02-22 | GSE154895 | GEO
Project description:Sivakumar2011 - Notch Signaling Pathway
Notch is a transmembrane receptor that mediates local cell-cell communication and coordinates a signaling cascade. It plays a key role in modulating cell fate decisions throughout the development of invertebrate and vertebrate species and the misregulation leads to a number of human diseases.
References:
Notch signaling: from the outside in.
Notch signaling in hematopoiesis and early lymphocyte development.
An overview of the Notch signalling pathway.
Notch and cancer: best to avoid the ups and downs.
Notch signaling: control of cell communication and cell fate.
This model is described in the article:
A systems biology approach to model neural stem cell regulation by notch, shh, wnt, and EGF signaling pathways.
Sivakumar KC, Dhanesh SB, Shobana S, James J, Mundayoor S.
Omics: a Journal of Integrative Biology. 2011; 15(10):729-737
Abstract:
The Notch, Sonic Hedgehog (Shh), Wnt, and EGF pathways have long been known to influence cell fate specification in the developing nervous system. Here we attempted to evaluate the contemporary knowledge about neural stem cell differentiation promoted by various drug-based regulations through a systems biology approach. Our model showed the phenomenon of DAPT-mediated antagonism of Enhancer of split [E(spl)] genes and enhancement of Shh target genes by a SAG agonist that were effectively demonstrated computationally and were consistent with experimental studies. However, in the case of model simulation of Wnt and EGF pathways, the model network did not supply any concurrent results with experimental data despite the fact that drugs were added at the appropriate positions. This paves insight into the potential of crosstalks between pathways considered in our study. Therefore, we manually developed a map of signaling crosstalk, which included the species connected by representatives from Notch, Shh, Wnt, and EGF pathways and highlighted the regulation of a single target gene, Hes-1, based on drug-induced simulations. These simulations provided results that matched with experimental studies. Therefore, these signaling crosstalk models complement as a tool toward the discovery of novel regulatory processes involved in neural stem cell maintenance, proliferation, and differentiation during mammalian central nervous system development. To our knowledge, this is the first report of a simple crosstalk map that highlights the differential regulation of neural stem cell differentiation and underscores the flow of positive and negative regulatory signals modulated by drugs.
This model is hosted on BioModels Database and identified by: BIOMD0000000396.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models.
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.
2011-11-02 | BIOMD0000000396 | BioModels
Project description:There is a gradient of β-catenin expression along the colonic crypt axis with the highest levels at the crypt bottom. However, it remains unclear whether different levels of canonical Wnt signaling exert distinct roles in the colonic epithelium. In the present study, we first showed that the canonical Wnt signaling is active in the proliferative compartment of normal colonic crypts by separating actively proliferating progenitor cells from non-proliferating cells in the colon using transgenic mice expressing a histone H2B-green fluorescent protein (GFP) fusion protein under the control of a tetracycline responsive regulatory element. Subsequently, we investigated the dose-dependent effect of canonical Wnt activation on colonic epithelial differentiation by controlling the expression levels of stabilized β-catenin using a doxycycline-inducible transgenic system in mice. We show that elevated levels of Wnt signaling induce the amplification of Lgr5+ cells, which is accompanied by crypt fission and a reduction in cell proliferation among progenitor cells. In contrast, lower levels of β-catenin induction enhanced cell proliferation rates of epithelial progenitors without affecting crypt fission rates. Notably, slow-cycling cells produced by β-catenin activation exhibit activation of Notch signaling and the treatment of β-catenin expressing mice with a Notch inhibitor turned such slow-cycling cells into actively proliferating cells. Our results indicate that the activation of the canonical Wnt signaling pathway is sufficient for de novo crypt formation, and suggest that different levels of canonical Wnt activations, in cooperation with Notch signaling, establish a hierarchy of slower-cycling stem cells and faster-cycling progenitor cells characteristic for the colonic epithelium.
2013-01-22 | GSE41688 | GEO
Project description:Developing a model of primate neural tube (NT) development is important to promote many NT disorder studies in model organisms. Here, we report a robust and stable system to allow for clonal expansion of single monkey neuroepithelial stem cells (NESCs) to develop into miniature NT-like structures. Single NESCs can produce functional neurons in vitro, survive and extensively regenerate neuron axons in monkey brain. NT formation and NESC maintenance depend on high metabolism activity and Wnt signaling. NESCs are regionally restricted into a telencephalic fate. Moreover, single NESCs can turn into radial glial progenitors (RGPCs). The transition is accurately regulated by Wnt signaling through regulation of Notch signaling and adhesion molecules. Finally, using the â??NESC-TO-NTsâ?? system, we model the functions of folic acid (FA) on NT closure and demonstrate FA can regulate multiple mechanisms to prevent NT defects. Together, our system is ideal for studying NT development and diseases. compare gene expression profiles in monkey neuroepithelial stem cells (NESCs), newly converted radial glial progenitor cells (RPGCs) from NESCs and differentiated neurons from NESCs
2015-11-21 | E-GEOD-73892 | biostudies-arrayexpress
Project description:There is a gradient of M-NM-2-catenin expression along the colonic crypt axis with the highest levels at the crypt bottom. However, it remains unclear whether different levels of canonical Wnt signaling exert distinct roles in the colonic epithelium. In the present study, we first showed that the canonical Wnt signaling is active in the proliferative compartment of normal colonic crypts by separating actively proliferating progenitor cells from non-proliferating cells in the colon using transgenic mice expressing a histone H2B-green fluorescent protein (GFP) fusion protein under the control of a tetracycline responsive regulatory element. Subsequently, we investigated the dose-dependent effect of canonical Wnt activation on colonic epithelial differentiation by controlling the expression levels of stabilized M-NM-2-catenin using a doxycycline-inducible transgenic system in mice. We show that elevated levels of Wnt signaling induce the amplification of Lgr5+ cells, which is accompanied by crypt fission and a reduction in cell proliferation among progenitor cells. In contrast, lower levels of M-NM-2-catenin induction enhanced cell proliferation rates of epithelial progenitors without affecting crypt fission rates. Notably, slow-cycling cells produced by M-NM-2-catenin activation exhibit activation of Notch signaling and the treatment of M-NM-2-catenin expressing mice with a Notch inhibitor turned such slow-cycling cells into actively proliferating cells. Our results indicate that the activation of the canonical Wnt signaling pathway is sufficient for de novo crypt formation, and suggest that different levels of canonical Wnt activations, in cooperation with Notch signaling, establish a hierarchy of slower-cycling stem cells and faster-cycling progenitor cells characteristic for the colonic epithelium. To separate actively proliferating cells from non-proliferating cells in normal colon, we used transgenic mice expressing a histone H2B-GFP fusion protein under the control of a tetracycline responsive regulatory element (H2B-GFP mice). In H2B-GFP mice, all colonic crypt cells exhibited strong nuclear GFP signal 7 days after doxycycline administration. When doxycycline was withdrawn for 2 days after the labeling period, nuclear GFP signal was diluted in proliferating cells whereas non-proliferating cells retained GFP. GFPhigh non-proliferating and GFPlow proliferating epithelial cells were sorted from the isolated crypts by FACS for microarray analysis. In addition, to investigate the effects of acute Wnt activation in colon, we generated doxycycline-inducible M-NM-2-catenin mice. Colonic crypts were isolated from untreated mice and mice fed doxycycline in the drinking water (2.0 mg/ml) for 5 days and subjected to microarray analysis.
2013-01-22 | E-GEOD-41688 | biostudies-arrayexpress
Project description:Sivakumar2011_NeuralStemCellDifferentiation_Crosstalk
This model is generated by integrating
BIOMD0000000394
(EGFR),
BIOMD0000000395
(Hedgehog),
BIOMD0000000396
(Notch) and
BIOMD0000000397
(Wnt), to investigate the signalling crosstalk between the four
pathways.
This model is described in the article:
A systems biology approach
to model neural stem cell regulation by notch, shh, wnt, and
EGF signaling pathways.
Sivakumar KC, Dhanesh SB, Shobana S,
James J, Mundayoor S.
OMICS 2011 Oct; 15(10): 729-737
Abstract:
The Notch, Sonic Hedgehog (Shh), Wnt, and EGF pathways have
long been known to influence cell fate specification in the
developing nervous system. Here we attempted to evaluate the
contemporary knowledge about neural stem cell differentiation
promoted by various drug-based regulations through a systems
biology approach. Our model showed the phenomenon of
DAPT-mediated antagonism of Enhancer of split [E(spl)] genes
and enhancement of Shh target genes by a SAG agonist that were
effectively demonstrated computationally and were consistent
with experimental studies. However, in the case of model
simulation of Wnt and EGF pathways, the model network did not
supply any concurrent results with experimental data despite
the fact that drugs were added at the appropriate positions.
This paves insight into the potential of crosstalks between
pathways considered in our study. Therefore, we manually
developed a map of signaling crosstalk, which included the
species connected by representatives from Notch, Shh, Wnt, and
EGF pathways and highlighted the regulation of a single target
gene, Hes-1, based on drug-induced simulations. These
simulations provided results that matched with experimental
studies. Therefore, these signaling crosstalk models complement
as a tool toward the discovery of novel regulatory processes
involved in neural stem cell maintenance, proliferation, and
differentiation during mammalian central nervous system
development. To our knowledge, this is the first report of a
simple crosstalk map that highlights the differential
regulation of neural stem cell differentiation and underscores
the flow of positive and negative regulatory signals modulated
by drugs.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000398.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
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.
2011-11-02 | BIOMD0000000398 | BioModels
Project description:Modeling development and maturation of the human hippocampus in culture is crucial to elucidate the physiological and pathological mechanisms of its neurogenesis. We established human hippocampal cell cultures by means of controlled neuralization of human induced pluripotent stem cells (hiPSCs). The timely re-activation of WNT signaling in hiPSCs, which were previously driven toward a dorsal telencephalic identity by the combined inhibition of WNT, BMP and TGF-β signaling, produced neural progenitors with a gene expression signature typical of human embryonic dentate gyrus (DG) cells. Key markers of neurogenesis resulted downstream of the NOTCH and WNT pathway and were upregulated in these progenitors. Notably, we found that, in addition to continuous WNT signaling, a specific laminin isoform is crucial to prolonging DG stem state and to extend DG progenitor proliferation for over 200 days in vitro. In fact, transition from laminin 511 to mouse laminin inhibited cell proliferation and promoted the differentiation of DG cells. Interestingly, global gene expression profiles of early and late progenitor cells and neurons suggest that a niche of laminin 511 and WNT signaling is sufficient to maintain a cell population enriched in DG progenitor cells and neurons. Finally, the xenograft of human DG progenitors into the DG of adult immunosuppressed host mice produced efficient integration of neurons, which innervated CA3 layer cells with an area covered by synapses similar to the area covered by endogenous hippocampal neuron synapses. Our observations indicate that neurons produced in the established culture niche resemble bona-fide human DG neurons.
2022-08-22 | GSE199355 | GEO
Project description:Sivakumar2011_WntSignalingPathway
The secreted protein Wnt activates the
heptahelical receptor Frizzled on nieghboring cells. Activation of
Frizzled causes the recruitment of additional membrane proteins
which in turn result in 1) the activation of the protein
Dishevelled via phosphorylation and 2) the activation of a
heterotrimeric G protein of unknown type. Activation of Dishevelled
results in the down-regulation of the Beta-Catenin destruction
complex which causes ubiquitination of Beta-Catenin and its
ultimate degradation via the proteasome. Inhibition of the
Beta-Catenin destruction complex yields a higher cytosolic
concentration of Beta-Catenin, which enters the nucleus, binds
various transcriptional regulatory molecules including the TCF/LEF
class of proteins, and results in the transcription of TCF/LEF
target genes. Activation of the heterotrimeric G-protein pathway in
turn activates Phospholipase C which in turn catalyzes the
catalysis of PI(4,5)P2 into DAG and IP3.
Reference:
The Wnt
signalling pathway.
You Wnt
some, you lose some: oncogenes in the Wnt signaling
pathway.
Wnt
signaling pathway.
This model is described in the article:
A systems biology approach
to model neural stem cell regulation by notch, shh, wnt, and
EGF signaling pathways.
Sivakumar KC, Dhanesh SB, Shobana S,
James J, Mundayoor S.
OMICS 2011 Oct; 15(10): 729-737
Abstract:
The Notch, Sonic Hedgehog (Shh), Wnt, and EGF pathways have
long been known to influence cell fate specification in the
developing nervous system. Here we attempted to evaluate the
contemporary knowledge about neural stem cell differentiation
promoted by various drug-based regulations through a systems
biology approach. Our model showed the phenomenon of
DAPT-mediated antagonism of Enhancer of split [E(spl)] genes
and enhancement of Shh target genes by a SAG agonist that were
effectively demonstrated computationally and were consistent
with experimental studies. However, in the case of model
simulation of Wnt and EGF pathways, the model network did not
supply any concurrent results with experimental data despite
the fact that drugs were added at the appropriate positions.
This paves insight into the potential of crosstalks between
pathways considered in our study. Therefore, we manually
developed a map of signaling crosstalk, which included the
species connected by representatives from Notch, Shh, Wnt, and
EGF pathways and highlighted the regulation of a single target
gene, Hes-1, based on drug-induced simulations. These
simulations provided results that matched with experimental
studies. Therefore, these signaling crosstalk models complement
as a tool toward the discovery of novel regulatory processes
involved in neural stem cell maintenance, proliferation, and
differentiation during mammalian central nervous system
development. To our knowledge, this is the first report of a
simple crosstalk map that highlights the differential
regulation of neural stem cell differentiation and underscores
the flow of positive and negative regulatory signals modulated
by drugs.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000397.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
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.
2011-11-02 | BIOMD0000000397 | BioModels
Project description:The Wnt-signalling pathway is one of the core de-regulated pathways in chronic lymphocytic leukemia (CLL), activated in a subset of patients by somatic coding mutations. Here we describe an alternative mechanism of Wnt-activation in malignant B cells, mediated by Notch2 activity in mesenchymal stromal cells (MSC) in the tumor microenvironment. We identified that tumor cells specifically induce and activate Notch2 in MSCs. Notch2 orchestrates the expression of target genes essential for the activation of canonical Wnt-signaling in CLL cells. Mechanistically, stromal Notch2 mediates the stabilization of â-catenin by inhibiting the activation of Gsk3-â in malignant B cells. Pharmacological inhibition of the Wnt-pathway mitigates microenvironment-mediated survival of malignant B cells in vitro. Similarly, inhibition of Notch-signaling impaired survival of CLL cells and disease engraftment in a PDX mouse model. Notch2 activation in the tumour microenvironment is a pre-requisite for the GSK3-â dependent activation of the canonical Wnt-signaling in tumor cells.
2018-09-19 | PXD010401 | Pride