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In vivo T-box Transcription Factor Profiling Reveals Joint Regulation of Embryonic Neuro-mesodermal Bipotency

ABSTRACT: Brachyury (Xbra/Xbra3) knock-down embryos of the frog Xenopus tropicalis were profiled to quantify neuro-mesodermal cell fate switches at a transcriptional level.

ORGANISM(S): Xenopus tropicalis

PROVIDER: GSE48663 | GEO | 2013/09/19

SECONDARY ACCESSION(S): PRJNA210967

REPOSITORIES: GEO

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In vivo T-box Transcription Factor Profiling Reveals Joint Regulation of Embryonic Neuro-mesodermal Bipotency

Project description:Brachyury (Xbra/Xbra3) knock-down embryos of the frog Xenopus tropicalis were profiled to quantify neuro-mesodermal cell fate switches at a transcriptional level. Transcriptional profiling of Xbra/Xbra3 double morphants at early tadpole stage (RNA-Seq) in biological triplicates.

2013-09-19 | E-GEOD-48663 | biostudies-arrayexpress

In vivo T-box Transcription Factor Profiling Reveals Joint Regulation of Embryonic Neuro-mesodermal Bipotency.

Project description:We defined genome-wide regulatory inputs of the T-box transcription factors Brachyury (Xbra), Eomesodermin (Eomes) and VegT that maintain neuro-mesodermal stem cells and determine their bipotential fates in the Xenopus tropicalis frog embryo. Binding profiles for Xbra, Eomes and VegT in X. tropicalis embryos (ChIP-Seq)

2013-09-19 | E-GEOD-48560 | biostudies-arrayexpress

In vivo T-box Transcription Factor Profiling Reveals Joint Regulation of Embryonic Neuro-mesodermal Bipotency.

2013-09-19 | GSE48560 | GEO

Antagonistic activities of Sox2 and Brachyury control the fate choice of neuro-mesodermal progenitors

Project description:The spinal cord and mesodermal tissues of the trunk such as the vertebral column and skeletal musculature derive from neuro-mesodermal progenitors (NMPs). Sox2, Brachyury (T) and Tbx6 have been correlated with NMP potency and lineage choice, however, their exact role and interaction in these processes have not been revealed yet. Here we present a global analysis of NMPs and their descending lineages performed on purified cells from E8.5 wild-type and mutant embryos. We show that T, cooperatively with WNT signaling, controls the progenitor state and the switch towards the mesodermal fate. Sox2 acts antagonistically and promotes neural development. Tbx6 reinforces the mesodermal fate choice, represses the progenitor state and confers paraxial fate commitment. Our findings refine previous models and establish new concepts of the molecular principles of mammalian trunk development comprising NMP maintenance, lineage choice and mesoderm formation.

2017-08-17 | GSE93524 | GEO

Innate Immune Response and Off-Target Mis-splicing Are Common Morpholino-Induced Side Effects in Xenopus

Project description:We report on the implications of genetic KO versus MO-mediated KD of the mesoderm-specifying Brachyury paralogues in the Western clawed frog Xenopus tropicalis. While both KO and KD embryos fail to activate the same core gene regulatory network, resulting in virtually identical morphological defects, embryos injected with control or target MOs also show a systemic GC content dependent immune response and many off-target splicing defects.

2018-02-21 | GSE96655 | GEO

The lipodystrophic hotspot lamin A p.R482W mutation deregulates the mesodermal inducer T/Brachyury and early vascular differentiation gene networks

Project description:The p.R482W hotspot mutation in A-type nuclear lamins causes familial partial lipodystrophy of Dunnigantype (FPLD2), a lipodystrophic syndrome complicated by early-onset atherosclerosis. Molecular mechanisms underlying endothelial cell dysfunction conferred by the lamin A mutation remain elusive. However, lamin A regulates epigenetic developmental pathways and mutations could perturb these functions. Here, we demonstrate that lamin A R482W elicits endothelial differentiation defects in a developmental model of FPLD2. Genome modeling in fibroblasts from patients with FPLD2 caused by the lamin A R482W mutation reveals repositioning of the mesodermal regulator T/Brachyury locus towards the nuclear center relative to normal fibroblasts, suggesting enhanced activation propensity of the locus in a developmental model of FPLD2. Addressing this issue, we report phenotypic and transcriptional alterations in mesodermal and endothelial differentiation of induced pluripotent stem cells we generated from a patient with R482Wassociated FPLD2. Correction of the LMNA mutation ameliorates R482W-associated phenotypes and gene expression. Transcriptomics links endothelial differentiation defects to decreased Polycomb-mediated repression of the T/Brachyury locus and over-activation of T target genes. Binding of the Polycomb repressor complex PRC2 to T/Brachyury is impaired by the mutated lamin A network, which is unable to properly associate with the locus. This leads to a deregulation of vascular gene expression over time. By connecting a lipodystrophic hotspot lamin A mutation to a disruption of early mesodermal gene expression and defective endothelial differentiation, we propose that the mutation rewires the fate of several lineages, resulting in multitissue pathogenic phenotypes.

2018-02-17 | GSE98675 | GEO

Expression of known and predicted genes in tissues of Xenopus tropicalis (frog)

Project description:Expression of known and predicted genes in tissues of Xenopus tropicalis (frog) pooled from multiple healthy individuals.

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A mesodermal factor, T (Brachyury), specifies mouse germ cell fate by directly activating germline determinants

Project description:Germ cells ensure reproduction and heredity in metazoans. Primordial germ cells (PGCs) in mice are induced in pluripotent epiblasts by BMP4 and WNT3, yet their mechanism of action remains unclear. Here, using in vitro PGC specification system, we show that WNT3 induces many transcription factors associated with mesoderm in epiblast-like cells (EpiLCs) through b-CATENIN. Among these, T (BRACHYURY), a classical and conserved mesodermal factor, was essential for robust activation of Blimp1 and Prdm14, two of the germline determinants. T, but not SMAD1 or b-CATENIN/TCF1, binds distinct regulatory elements of both Blimp1 and Prdm14, and without BMP4 and WNT3, directly up-regulates these genes, consequently delineating downstream PGC program. Without BMP4, a program induced by WNT3 prevents T from activating Blimp1 and Prdm14, demonstrating that BMP4 is permissive for PGC specification. These findings establish a fundamental role of a mesodermal transcription factor in PGC specification, a potentially evolutionarily conserved mechanism across metazoans. Genome target search for transcription factors, SMAD1, T, and TCF1 on PGC-like cells

2013-12-11 | E-GEOD-50394 | biostudies-arrayexpress

Mus musculus

Project description:Antagonistic activities of Sox2 and Brachyury control the fate choice of neuro-mesodermal progenitors

| PRJNA360989 | ENA

A mesodermal factor, T (Brachyury), specifies mouse germ cell fate by directly activating germline determinants

2013-12-11 | GSE50394 | GEO