Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Variability of an early developmental cell population underlies stochastic laterality defects

ABSTRACT: Embryonic development seemingly proceeds with almost perfect precision. However, it is largely unknown how much microscopic variability is hidden beneath this macroscopic accuracy. Here, we quantified embryo-to-embryo variability in vertebrate development, by studying cell number variation in the zebrafish endoderm. We noticed that the size of a sub-population of the endoderm, the dorsal forerunner cells (which later forms the left-right organizer), is highly variable between individual embryos. We found that the frequency of left-right laterality defects is increased drastically in embryos with a low number of dorsal forerunner cells, and we observed that these fluctuations are largely stochastic. Hence, a stochastic variation in early development leads to a remarkably strong macroscopic phenotype. These fluctuations appear to be caused by variable deposition of maternal factors involved in specification of the dorsal forerunner cells. In summary, we here dissect cause and consequence of embryo-to-embryo variability in a vertebrate model.

ORGANISM(S): Danio rerio

PROVIDER: GSE153621 | GEO | 2020/12/08

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Transcription factor fluctuations underlie cell-to-cell variability in the Hedgehog response [bulk-RNAseq]

Project description:Stochastic differences among clonal cells can initiate cell fate decisions in development or cause cell-to-cell differences in the responses to drugs or extracellular ligands. We hypothesize that some of this phenotypic variability is caused by stochastic fluctuations in the activities of transcription factors. We tested this hypothesis in NIH3T3-CG cells using the response to Hedgehog signaling as a model cellular response. Here we present evidence for the existence of distinct fast and slow responding substates of NIH3T3-CG cells. These two substates have distinct expression profiles, and fluctuations in the activity of the Prrx1 transcription factor (TF) underlie some of the differences in expression and responsiveness between fast and slow cells. We speculate that similar variability in other TFs may underlie other phenotypic differences among genetically identical cells.

2022-06-18 | GSE206154 | GEO

Transcription factor fluctuations underlie cell-to-cell variability in the Hedgehog response

2022-05-19 | GSE203134 | GEO

Floc'hlay2020 - SeaUrchin_model_ginsim

Project description:Multilevel logical model encompassing the Nodal and BMP pathways together with key transcription factors setting the dorsal-ventral axis in the sea urchin P. lividus embryo. This model accounts for the specification of wild-type ventral ectoderm, ciliary band and dorsal ectoderm, and further recapitulates sophisticated mutant phenotypes.

2021-01-06 | MODEL2002190001 | BioModels

Role of maternal Wnt11b in cortical rotation and axis formation

Project description:Asymmetric signalling centres in the early embryo are essential for axis formation in vertebrates. These regions, namely the dorsal morula, yolk syncytial layer, and distal hypoblast/anterior visceral endoderm (in amphibians, teleosts and mammals, respectively), require the localised stabilisation of nuclear Beta-catenin (Ctnnb1), implying that localised Wnt/Beta-catenin signalling activity is critical in their establishment. However, it is becoming increasingly apparent that the stabilisation of Beta-catenin in this context may be initiated independently of secreted Wnt growth factor activity. In Xenopus, dorsal Beta-catenin stabilisation is initiated by a requisite microtubule-mediated symmetry-breaking event in the fertilised egg: “cortical rotation”. Vegetally-localised wnt11b mRNA has been implicated upstream of Beta-catenin in this context, as has the dorsal enrichment of Wnt ligand-independent activators of Beta-catenin, but the extent that each of these processes contribute to axis formation in this paradigm remains unclear. Here we describe a maternal effect mutation in Xenopus laevis wnt11b.L, generated by CRISPR mutagenesis. We demonstrate a maternal requirement for timely and complete gastrulation morphogenesis and a zygotic requirement for proper left-right asymmetry. We also show that a subset of maternal wnt11b mutants have axis and dorsal gene expression defects, and we find that microtubule assembly and cortical rotation are reduced in wnt11b mutant eggs, leading to less organised and directed vegetal microtubule arrays. mRNA sequencing was used to determine the extent of dorsal and other gene dysregulation during gastrulation.

2022-05-02 | GSE195806 | GEO

RNA-seq of zebrafish embryo dorsal forerunner cells lacking Vestigial like 4 like (Vgll4l) or Yes associated protein 1 (Yap1)/ WW domain containing transcription regulator 1 (Wwtr1/Taz) activities

Project description:Purpose: The goals of this study are to compare control Dorsal Forerunner Cells (DFCs) transcriptome (RNA-seq) to the one of embryos depleted for either Vgll4l or Yap/Taz (Yap1 and Wwtr1) and to evaluate the transcriptional contribution of these transcription cofactors to the formation of the zebrafish left right organizer Methods: Knockdown (KD) of Vgll4l and Yap/Taz were performed by injection of morpholinos in Tg(sox17:GFP) embryos at the one cell stage. Single DFCs cluster were dissected out at 90% epiboly. Extraction of Total RNA and cDNA libraries construction were done using SMART-Seq® v4 Ultra® Low Input RNA Kit for Sequencing from clontech and NEB DNA Ultra library construction kit. Whole genome sequencing was done on illumina Hiseq 2000 sequencer. Results/Conclusions: Vgll4l and Yap/ Taz play and essential role in the formation of the left right organizer. They regulate a large number of genes important for differentiation of the organ. They are required for proper expression of major transciprition factors involved in Kupffer vesicle formation as well as for genes involved in ciliogenesis. Both Vgll4l and Yap/Taz act upstream of major pathways known to regulate the formation of the left right organizer. Additionally, Vgll4l is required for the spatio-temporal expression of writters and readers of DNA methylation marks (DNA methylation enzymes and methyl CpG binding proteins) during Kupffer's vesicle differentiation

2019-09-19 | GSE119623 | GEO

Nanog-dependent feedback loops regulate murine embryonic stem cell heterogeneity

Project description:A number of key regulators of mouse embryonic stem (ES) cell identity, including the transcription factor Nanog, show strong expression fluctuations at the single cell level. The molecular basis for these fluctuations is unknown. Here we used a genetic complementation strategy to investigate expression changes during transient periods of Nanog downregulation. Employing an integrated approach, that includes high-throughput single cell transcriptional profiling and mathematical modelling, we found that early molecular changes subsequent to Nanog loss are stochastic and reversible. However, analysis also revealed that Nanog loss severely compromises the self-sustaining feedback structure of the ES cell regulatory network. Consequently, these nascent changes soon become consolidated to committed fate decisions in the prolonged absence of Nanog. Consistent with this, we found that exogenous regulation of Nanog-dependent feedback control mechanisms produced more a homogeneous ES cell population. Taken together our results indicate that Nanog-dependent feedback loops play a role in controlling both ES cell fate decisions and population variability.

2012-08-30 | GSE40335 | GEO

Construction of a Mammalian Embryo from Embryonic Stem Cells Instructed by Morphogen Gradients

Project description:Generating properly organized and differentiated embryonic structures in vitro from aggregates of pluripotent cells remains a major challenge. In a living embryo, the interplay in between signaling molecules known as morphogens and their antagonists lead to gradients of activity that instruct cells about their fate, leading to patterning and morphogenesis. Here we show that experimentally engineering a morphogen signaling center within an aggregate of mouse pluripotent stem cells is sufficient to mimic the function of an embryo organizer and to trigger embryonic development. The resulting embryoids are remarkably well patterned along anterior-posterior and dorsal-ventral axes, generate three germ layers through a process of gastrulation and differentiate germ layer derivatives (including notochord, vasculature, neural tube, neural crest, endoderm) similar to an authentic embryo at E9-E9.5.

2021-04-25 | GSE142309 | GEO

Mus musculus

Project description:mouse embryo dorsal midbrain development

| PRJDB12123 | ENA

Transcriptome analysis of dorsal root ganglion in rats with knee rheumatoid arthritis

Project description:To determine the LncRNA expression profile in dorsal root ganglia tissues of 7 days after rats received 150 μl of CFA (1 mg/ml Mycobacterium tuberculosis, Sigma, USA) through the patella tendon into the right knee joint. CFA injection rats macthed saline injection rats, we uesed LncRNA microArray analysis form Arraystar to examine the expression of LncRNAs and mRNAs in dorsal root ganglia tissues of 7 days after rats received CFA through the patella tendon into the right knee joint and matched Saline through the patella tendon into the right knee joint.

2020-11-12 | GSE146881 | GEO

Regulation of posterior body and ectodermal morphogenesis in zebrafish by localized Yap1 and Wwtr1

Project description:The vertebrate embryo undergoes a series of dramatic morphological changes as the body extends to form the complete anterior-posterior axis during the somite-forming stages. The molecular mechanisms regulating these complex processes are still largely unknown. We show that the Hippo pathway transcriptional coactivators Yap1 and Wwtr1 are specifically localized to the ectoderm and notochord, and play a critical and unexpected role in posterior body extension by regulating the assembly of Fibronectin underneath the ectoderm and surrounding the notochord. We also find that Yap1/Wwtr1, also acting through Fibronectin, have an essential role in the ectodermal morphogenesis necessary to form the initial dorsal and ventral fins, a process that had been thought to involve bending of an epithelial sheet, but which we now show involves active cell migration. Our results reveal how the Hippo pathway transcriptional program, localized to two specific tissues, acts to control essential morphological events in the vertebrate embryo.

2018-02-14 | GSE102606 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data