Mesenchymal-epithelial crosstalk shapes intestinal regionalisation via Wnt and Shh signalling
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA761659 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Mesenchymal-epithelial crosstalk shapes intestinal regionalisation via Wnt and Shh signalling [RNA-seq]
| PRJNA761131 | ENA
Project description:In the small intestine (SI), regionalisation enables sequential processing of food and nutrient absorption. To characterise the basis for region-specific mesenchymal-epithelial crosstalks during late small intestinal morphogenesis, we combined transcriptional profiling of epithelial and mesenchymal cell populations isolated from different intestinal regions with ChIP-seq, 3D imaging and functional ex vivo and organoid studies. We find that a mesenchymal PDGFRA-high population located in close proximity to the developing epithelium is enriched for genes involved in signalling and support the epithelium in a region-specific manner via the establishment of a proximal to distal gradient of epithelial Wnt activity. Furthermore, we provide evidence that Wnt signalling in the distal SI directly regulates epithelial expression of Sonic Hedgehog (SHH), which in turn acts on mesenchymal cells driving villi formation. Our results therefore uncover a mechanistic link between Wnt and Hedgehog signalling across different cellular compartments central for anterior-posterior regionalisation and correct organ formation.
2021-12-11 | GSE183532 | GEO
Project description:Hypothesis and proof of concept:
Our hypothesis is that increase in cellular iron import proteins (TfR1, DMT1) occur early in the adenoma-carcinoma sequence through mutations in APC and lead to cellular iron loading. As demonstrated in our previous work the effects of this iron loading is to mediate increased Wnt signalling resulting in c-myc induction. This in turn serves to increase the expression of iron import proteins (TfR1, DMT1) and decrease the expression of iron export (ferroportin [FPN]) and storage (ferritin) proteins. Such a hypothesis explains how Wnt signalling controls iron metabolism and ensures that there is adequate cellular iron for ATP generation and cellular proliferation.
Experimental design:
To test such a hypothesis we aim to prospectively collect the following colorectal tissue from patients attending for colonoscopy:
1. Normal colonic mucosa in patients with no colorectal pathology (n = 30)
2. Polyps and matched normal colon (n = 30)
3. Colorectal cancers and matched normal colon (n = 30)
We also intend to collect serum and urine from the following patient groups:
4. Normal colonoscopy (n = 30)
5. Colorectal adenomas (n = 30)
6. Colorectal cancers (n = 30)
Primary outcome(s): Measured at baseline, using the expression of proteins in the tissue and serum to detect the cellular and systemic iron transport proteins. The techniques used will include mass spectrometry, western blotting, real time PCR and immunohistochemistry.
| 2416626 | ecrin-mdr-crc
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-12-11 | GSE183671 | GEO
Project description:Millions of sweat glands required to maintain body temperature develop from embryonic ectoderm by a poorly defined mechanism. We present evidence for temporal cascade regulation of sweat gland development by Wnt, Eda and Shh pathways. The first stage, sweat gland induction, failed completely when Wnt/?-catenin signaling was blocked in skin epithelium, accompanied by sharp downregulation of Wnt, Eda and Shh pathway genes. In a meta-layer of regulation, Wnt antagonist Dkk4 appeared to operate on sweat gland induction in a negative feedback loop: Dkk4 was itself sharply downregulated in ?-catenin-ablated mice, whereas its over-expression repressed Wnt target genes and significantly reduced gland numbers. Eda signaling succeeded Wnt, and activated downstream Shh pathway. Thus, in absence of Eda, Wnt pathway was still active and initial sweat gland pre-germs were seen but failed to develop germs, and dwonstream Shh pathway was repressed. When both Wnt and Eda were intact but Shh was ablated, early stage induction and subsequent duct formation occurred normally, but the final stage formation of secretory coil failed. Thus, sweat gland development shows a relay of regulatory steps, initiated by Wnt/?-catenin -- itself modulated by Dkk4 -- with subsequent tandem action of Eda and Shh pathways. Compared expression changes between WT and skin specific Dkk4 transgenic footpads at 2 developmental time points, E15.5 and E16.5. Data were duplicated with 2 sets of samples.
2014-08-20 | E-GEOD-50862 | biostudies-arrayexpress
Project description:Millions of sweat glands required to maintain body temperature develop from embryonic ectoderm by a poorly defined mechanism. We present evidence for temporal cascade regulation of sweat gland development by Wnt, Eda and Shh pathways. The first stage, sweat gland induction, failed completely when Wnt/β-catenin signaling was blocked in skin epithelium, accompanied by sharp downregulation of Wnt, Eda and Shh pathway genes. In a meta-layer of regulation, Wnt antagonist Dkk4 appeared to operate on sweat gland induction in a negative feedback loop: Dkk4 was itself sharply downregulated in β-catenin-ablated mice, whereas its over-expression repressed Wnt target genes and significantly reduced gland numbers. Eda signaling succeeded Wnt, and activated downstream Shh pathway. Thus, in absence of Eda, Wnt pathway was still active and initial sweat gland pre-germs were seen but failed to develop germs, and dwonstream Shh pathway was repressed. When both Wnt and Eda were intact but Shh was ablated, early stage induction and subsequent duct formation occurred normally, but the final stage formation of secretory coil failed. Thus, sweat gland development shows a relay of regulatory steps, initiated by Wnt/β-catenin -- itself modulated by Dkk4 -- with subsequent tandem action of Eda and Shh pathways. Compared expression changes between wild type and skin specific beta-catenin knockout footpads at 3 developmental time points, E15.5, E16.5 and E17.5. Data were duplicated with 2 sets of samples.
2014-08-20 | E-GEOD-50859 | biostudies-arrayexpress
Project description:Millions of sweat glands required to maintain body temperature develop from embryonic ectoderm by a poorly defined mechanism. We present evidence for temporal cascade regulation of sweat gland development by Wnt, Eda and Shh pathways. The first stage, sweat gland induction, failed completely when Wnt/β-catenin signaling was blocked in skin epithelium, accompanied by sharp downregulation of Wnt, Eda and Shh pathway genes. In a meta-layer of regulation, Wnt antagonist Dkk4 appeared to operate on sweat gland induction in a negative feedback loop: Dkk4 was itself sharply downregulated in β-catenin-ablated mice, whereas its over-expression repressed Wnt target genes and significantly reduced gland numbers. Eda signaling succeeded Wnt, and activated downstream Shh pathway. Thus, in absence of Eda, Wnt pathway was still active and initial sweat gland pre-germs were seen but failed to develop germs, and dwonstream Shh pathway was repressed. When both Wnt and Eda were intact but Shh was ablated, early stage induction and subsequent duct formation occurred normally, but the final stage formation of secretory coil failed. Thus, sweat gland development shows a relay of regulatory steps, initiated by Wnt/β-catenin -- itself modulated by Dkk4 -- with subsequent tandem action of Eda and Shh pathways.
2014-08-20 | GSE50862 | GEO
Project description:Millions of sweat glands required to maintain body temperature develop from embryonic ectoderm by a poorly defined mechanism. We present evidence for temporal cascade regulation of sweat gland development by Wnt, Eda and Shh pathways. The first stage, sweat gland induction, failed completely when Wnt/β-catenin signaling was blocked in skin epithelium, accompanied by sharp downregulation of Wnt, Eda and Shh pathway genes. In a meta-layer of regulation, Wnt antagonist Dkk4 appeared to operate on sweat gland induction in a negative feedback loop: Dkk4 was itself sharply downregulated in β-catenin-ablated mice, whereas its over-expression repressed Wnt target genes and significantly reduced gland numbers. Eda signaling succeeded Wnt, and activated downstream Shh pathway. Thus, in absence of Eda, Wnt pathway was still active and initial sweat gland pre-germs were seen but failed to develop germs, and dwonstream Shh pathway was repressed. When both Wnt and Eda were intact but Shh was ablated, early stage induction and subsequent duct formation occurred normally, but the final stage formation of secretory coil failed. Thus, sweat gland development shows a relay of regulatory steps, initiated by Wnt/β-catenin -- itself modulated by Dkk4 -- with subsequent tandem action of Eda and Shh pathways.
2014-08-20 | GSE50859 | GEO
Project description:WNT signalling activity on epiblast cells
| PRJNA401007 | ENA
Project description:The function of the FAM83F protein, like the functions of many members of the FAM83 family, is poorly understood. Here we show that injection of Fam83f mRNA into Xenopus embryos causes axis duplication, a phenotype indicative of enhanced Wnt signalling. Consistent with this, overexpression of FAM83F activates Wnt signalling, whilst ablation of FAM83F from human colorectal cancer (CRC) cells attenuates it. We demonstrate that FAM83F is farnesylated and interacts and co-localises with CK1α at the plasma membrane. This interaction with CK1α is essential for FAM83F to activate Wnt signalling, and FAM83F mutants that do not interact with CK1α fail to induce axis duplication in Xenopus embryos and to activate Wnt signalling in cells. FAM83F acts upstream of GSK-3β, because the attenuation of Wnt signalling caused by loss of FAM83F can be rescued by GSK-3 inhibition. Introduction of a farnesyl-deficient mutant of FAM83F in cells through CRISPR/Cas9 genome editing redirects the FAM83F-CK1α complex away from the plasma membrane and significantly attenuates Wnt signalling, indicating that FAM83F exerts its effects on Wnt signalling at the plasma membrane.
2020-12-23 | PXD023121 | Pride