Gallus gallus
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ABSTRACT:
PROVIDER: PRJNA230930 | ENA |
REPOSITORIES: ENA
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Project description:The generation of diverse neuronal types and subtypes from multipotent progenitors during development is crucial for assembling functional neural circuits in the adult central nervous system. It is well known that Notch signalling pathway through the inhibition of proneural genes is a key regulator of neurogenesis in the vertebrate central nervous system. However, its role during hypothalamus formation along with its downstream effectors remains poorly defined. Here, we have transiently blocked Notch activity in chick embryos and used global gene expression analysis to provide evidence that Notch signalling modulates the generation of neurons in the early developing hypothalamus by lateral inhibition. Most importantly, we have taken advantage of this model to identify novel targets of Notch signalling, such as Tagln3 and Chga, which were expressed in hypothalamic neuronal nuclei. This data gives essential advances into the early generation of neurons in the hypothalamus. We demonstrate that inhibition of Notch signalling during early development of the hypothalamus enhances expression of several new markers. These genes must be considered as important new targets of the Notch/proneural network. Four sets of samples were used for analysing transcriptome changes in DAPT treated chicl embryos. The rostral part of the head (including the anterior forebrain, optic vesicles and overlying tissue) was collected from control embryos and DAPT-treated embryos at stage HH13.
2013-12-10 | E-GEOD-53129 | biostudies-arrayexpress
Project description:This randomized phase I/II clinical trial is studying the side effects and best dose of gamma-secretase/notch signalling pathway inhibitor RO4929097 when given together with vismodegib and to see how well they work in treating patients with advanced or metastatic sarcoma. Vismodegib may slow the growth of tumor cells. Gamma-secretase/notch signalling pathway inhibitor RO4929097 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving vismodegib together with gamma-secretase/notch signalling pathway inhibitor RO4929097 may be an effective treatment for sarcoma.
| 2091475 | ecrin-mdr-crc
Project description:Dysregulated Notch signalling contributes to breast cancer development and progression, but validated tools to measure the level of Notch signalling in breast cancer subtypes and in response to systemic therapy are largely lacking. A transcriptomic signature of Notch signalling would thus be warranted, and in this report, we have established such a classifier. To generate the signature, we first identified Notch-regulated genes from six basal-like breast cancer cell lines subjected to elevated and reduced Notch signalling by culturing on immobilized Notch ligand Jagged1 or blockade of Notch by -secretase inhibitors, respectively. From this cadre of Notch-regulated genes, we developed candidate transcriptomic signatures that were trained on a breast cancer patient dataset (the TCGA-BRCA cohort) and an optimal 20-gene signature was selected from analysis of the transcriptomes of a broader breast cancer cell line cohort. We validated the signature on two independent patient datasets (METABRIC and Oslo2) and it showed an improved coherence score and tumour specificity compared with previously published signatures. Furthermore, the signature score was particularly high for basal-like breast cancer, indicating an enhanced level of Notch signalling in this subtype. The signature score was increased after neoadjuvant treatment in the PROMIX and BEAUTY patient cohorts, and a lower signature score generally correlated with better clinical outcome. Collectively, the 20-gene transcriptional signature has the potential to better stratify patients and to evaluate the response of future Notch-based therapies for breast cancer.
2024-01-05 | GSE235052 | GEO
Project description:Dysregulated Notch signalling contributes to breast cancer development and progression, but validated tools to measure the level of Notch signalling in breast cancer subtypes and in response to systemic therapy are largely lacking. A transcriptomic signature of Notch signalling would thus be warranted, and in this report, we have established such a classifier. To generate the signature, we first identified Notch-regulated genes from six basal-like breast cancer cell lines subjected to elevated and reduced Notch signalling by culturing on immobilized Notch ligand Jagged1 or blockade of Notch by -secretase inhibitors, respectively. From this cadre of Notch-regulated genes, we developed candidate transcriptomic signatures that were trained on a breast cancer patient dataset (the TCGA-BRCA cohort) and an optimal 20-gene signature was selected from analysis of the transcriptomes of a broader breast cancer cell line cohort. We validated the signature on two independent patient datasets (METABRIC and Oslo2) and it showed an improved coherence score and tumour specificity compared with previously published signatures. Furthermore, the signature score was particularly high for basal-like breast cancer, indicating an enhanced level of Notch signalling in this subtype. The signature score was increased after neoadjuvant treatment in the PROMIX and BEAUTY patient cohorts, and a lower signature score generally correlated with better clinical outcome. Collectively, the 20-gene transcriptional signature has the potential to better stratify patients and to evaluate the response of future Notch-based therapies for breast cancer.
2024-01-05 | GSE236749 | GEO
Project description:The Notch signalling pathway plays fundamental roles in diverse developmental processes in metazoans, where it is important in driving cell fate and directing differentiation of various cell types. However, we still have limited knowledge about the role of Notch in early preimplantation stages of mammalian development, or how it interacts with other signalling pathways active at these stages such as Hippo. By using genetic and pharmacological tools in vivo, together with image analysis of single embryos and pluripotent cell culture, we have found that Notch is active from the 4-cell stage. Transcriptomic analysis in single morula identified novel Notch targets, such as early naïve pluripotency markers or transcriptional repressors such as TLE4. Our results reveal a previously undescribed role for Notch in driving transitions during the gradual loss of potency that takes place in the early mouse embryo prior to the first lineage decisions.
2019-04-24 | GSE121979 | GEO
Project description:The Notch signaling pathway functions in a number of processes during embryologic development, especially the maintenance or aquisition of cell fate. We purturb the Notch signalling pathway in embryonic Xenopus laevis in order to 1) better characterize the downstream targets of Notch signalling, and 2) determine the extent to which early embryos can recover from transient purturbations to critical signalling pathways, if at all. Xenopus laevis embryos were unilaterally injected at the two cell stage with either GFP, GFP and ICD (Notch intracellular domain, an up-regulator of the Notch pathway), or GFP and DBM (domain-binding mutant, a downregulator of the Notch pathway). At stages 18, 28, and 38, for each injection, pooled total RNA from 10 embryos was extracted. Extraction was performed for three biological replicates for each time/injection condition. cDNA from total RNA was hybridized on Affymetrix Xenopus laevis Genome 2.0 arrays.
2014-08-06 | E-GEOD-60127 | biostudies-arrayexpress
Project description:The Notch signaling pathway functions in a number of processes during embryologic development, especially the maintenance or aquisition of cell fate. We purturb the Notch signalling pathway in embryonic Xenopus laevis in order to 1) better characterize the downstream targets of Notch signalling, and 2) determine the extent to which early embryos can recover from transient purturbations to critical signalling pathways, if at all.
2014-08-06 | GSE60127 | GEO
Project description:Transcriptomic analysis of murine embryos lacking endogenous retinoic acid signaling
| PRJNA186749 | ENA
Project description:GAS1 is required for Notch-dependent facilitation of SHH signalling in forebrain development
| PRJEB43666 | ENA
Project description:The generation of diverse neuronal types and subtypes from multipotent progenitors during development is crucial for assembling functional neural circuits in the adult central nervous system. It is well known that Notch signalling pathway through the inhibition of proneural genes is a key regulator of neurogenesis in the vertebrate central nervous system. However, its role during hypothalamus formation along with its downstream effectors remains poorly defined. Here, we have transiently blocked Notch activity in chick embryos and used global gene expression analysis to provide evidence that Notch signalling modulates the generation of neurons in the early developing hypothalamus by lateral inhibition. Most importantly, we have taken advantage of this model to identify novel targets of Notch signalling, such as Tagln3 and Chga, which were expressed in hypothalamic neuronal nuclei. This data gives essential advances into the early generation of neurons in the hypothalamus. We demonstrate that inhibition of Notch signalling during early development of the hypothalamus enhances expression of several new markers. These genes must be considered as important new targets of the Notch/proneural network.
2013-12-10 | GSE53129 | GEO