Transient Nodal signalling in left precursors coordinates opposed asymmetries shaping the heart loop
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PROVIDER: PRJNA623301 | ENA |
REPOSITORIES: ENA
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Project description:The secreted factor Nodal has been shown to be a major left determinant. Although it is associated with severe congenital heart defects, its role in heart morphogenesis has remained poorly understood. Here, we report that Nodal is transiently active in precursors of the mouse heart tube poles, before the morphological changes of heart looping. In conditional mutants, we show that Nodal is not required to initiate asymmetric morphogenesis. We provide evidence of a heart-specific random generator of asymmetry that is independent of Nodal. Using 3D quantifications and simulations, we demonstrate that Nodal functions as a bias of this mechanism: it is required to amplify and coordinate opposed left-right asymmetries at the heart tube poles, thus generating a robust helical shape. We identify downstream effectors of Nodal signalling, regulating asymmetries in cell proliferation, cell differentiation and extra-cellular matrix composition. Our work provides novel insight into how Nodal regulates asymmetric organogenesis.
2020-11-09 | GSE148123 | GEO
Project description:ZIC2 Is Required For Nodal Expression And The Establishment Of Left-Sided Identity
| PRJNA416367 | ENA
Project description:Left and Right phrenic nerves, which innervate the left and right diaphragm muscles, exhibit different innervation patterns. This left/right (L/R) asymmetry is established at the onset of innervation by a developmental program that requires Nodal. Phenotype analysis suggests that the cervical motoneurons, which innervate the diaphragm, have a L/R imprint that contributes to set the L/R asymmetries of innervation. We used microarray to analyze the expression profile of left and right cervical motoneurons before diaphragm innervation
2017-06-08 | GSE84778 | GEO
Project description:In this experiment patterns of chromatin accessibility were compared in P19 mouse embryonic teratoma cells treated with either the Nodal/Activin singalling inhibitor SB-431542, or with Activin for 1hr (acute signalling) and 8 hr (prolonged signalling), or left untreated (chronic signalling)
2022-04-10 | GSE178315 | GEO
Project description:The purpose of this study was to identify putative downstream targets of the transcription factor ZIC2 in the mouse embryo. The results indicate loss of NODAL pathway expression, consistent with the observed phenotype of right isomerism in heart, lungs and viscera.
2017-10-31 | GSE106350 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE32231: Molecular characterization of Nodal marginal zone lymphoma [Gene Expression] GSE32232: microRNA-expression profile in a series of Nodal marginal zone lymphoma patients [miRNA expression] Refer to individual Series
2011-09-20 | E-GEOD-32233 | biostudies-arrayexpress
Project description:Oncogenic PIK3CA mutations activate phosphoinositide 3-kinase (PI3K) and are among the commonest somatic mutations in cancer and mosaic, developmental overgrowth disorders. We recently demonstrated that the ‘hotspot’ variant PIK3CAH1047R exerts striking allele dose-dependent effects on stemness in human induced pluripotent stem cells (iPSCs), and moreover demonstrated multiple oncogenic PIK3CA copies in a substantial subset of human cancers. To identify the molecular mechanism underpinning PIK3CAH1047R allele dose-dependent stemness, we profiled isogenic wild-type, PIK3CAWT/H1047R and PIK3CAH1047R/H1047R iPSCs by high-depth transcriptomics, proteomics and reverse-phase protein arrays (RPPA). PIK3CAH1047R/H1047R iPSCs exhibited altered expression of 5644 genes and 248 proteins, whereas heterozygous hPSCs showed 492 and 54 differentially-expressed genes and proteins, respectively, confirming a nearly deterministic phenotypic effect of homozygosity for PIK3CAH1047R. Pathway and network-based analyses predicted a strong association between self-sustained TGFb/NODAL signaling and the ‘locked’ stemness phenotype induced by homozygosity for PIK3CAH1047R. This stemness gene signature was maintained without exogenous NODAL in PIK3CAH1047R/H1047R iPSCs and was reversed by pharmacological inhibition of TGFb/NODAL signaling but not by PIK3CA-specific inhibition. Analysis of PIK3CA-associated human breast cancers revealed increased expression of the stemness markers NODAL and POU5F1 as a function of disease stage and PIK3CAH1047R allele dosage. Together with emerging realization of the link between NODAL re-expression and aggressive cancer behavior, our data suggest that TGFb/NODAL inhibitors warrant testing in advanced breast tumors with multiple oncogenic PIK3CA copies.
2021-03-03 | PXD014719 | Pride
Project description:Despite the fundamental roles to cell fates determination in all metazoans, the mechanism by which the TGF-β family signaling is interpreted into spatial and temporal manner and multiple cell fates is still elusive. The cell context dependent function of TGF-β signaling largely relies on the transcriptional regulation centered by SMAD proteins. Here, we discovered that the DNA-repair related protein, HMCES contributes to early development by maintaining the nodal/activin or BMP signaling related transcriptome homeostasis. HMCES is a R-SMAD proteins binding partner that co-localizes with R-SMADs at active histone marks. However, HMCES chromatin occupancy is independent of nodal/activin or BMP signaling. Mechanically, HMCES exerts its transcriptional regulation role by counteracting R-SMAD proteins association with chromatin. In Xenopus embryo, hmces-KD causes dramatic development defects with altered left-right axis asymmetry along with increasing expression of lefty1. In sum, we disclosed the novel transcriptional regulatory function of HMCES integrated in TGF-β family signaling.
2022-09-14 | GSE186223 | GEO
Project description:Despite the fundamental roles to cell fates determination in all metazoans, the mechanism by which the TGF-β family signaling is interpreted into spatial and temporal manner and multiple cell fates is still elusive. The cell context dependent function of TGF-β signaling largely relies on the transcriptional regulation centered by SMAD proteins. Here, we discovered that the DNA-repair related protein, HMCES contributes to early development by maintaining the nodal/activin or BMP signaling related transcriptome homeostasis. HMCES is a R-SMAD proteins binding partner that co-localizes with R-SMADs at active histone marks. However, HMCES chromatin occupancy is independent of nodal/activin or BMP signaling. Mechanically, HMCES exerts its transcriptional regulation role by counteracting R-SMAD proteins association with chromatin. In Xenopus embryo, hmces-KD causes dramatic development defects with altered left-right axis asymmetry along with increasing expression of lefty1. In sum, we disclosed the novel transcriptional regulatory function of HMCES integrated in TGF-β family signaling.
2022-09-14 | GSE186222 | GEO
Project description:A comprehensive search for downstream genes is necessary for understanding of functions of Nodal signaling in embryos of the ascidian Ciona intestinalis. The level of mRNA expression in Nodal-overexpressing embryos was compared with that in normal embryos at the late gastrula stage by a microarray analysis. Overexpression of Ci-nodal elevated the level of expression of 115 genes more than two-fold. These candidate target genes include those encoding transcription factors, proteins involved in cell-cell communication, and extracellular matrix components. Many of these genes were expressed in the neural plate at the late gastrula stage. Overexpression of nodal also affected the expression of genes involved in the planar cell polarity pathway and Wnt/Ca2+ pathway (prickle, Rho-like2, and PLC2), and delta1-protocadherin-like. Keywords: ascidian, Ciona intestinalis, Nodal, embryogenesis, gene expression profile two samples Dye Swap design with 2 arrays
2010-05-15 | E-GEOD-14567 | biostudies-arrayexpress