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A 37 kb region upstream of Brachyury comprising a notochord enhancer is essential for notochord and tail development

ABSTRACT: A 37 kb region upstream of Brachyury comprising a notochord enhancer is essential for notochord and tail development

PROVIDER: PRJNA744512 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15064490_1.fastq.gz	Fastqsanger.gz
	SRR15064490_2.fastq.gz	Fastqsanger.gz

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A 37 kb region upstream of Brachyury comprising a notochord enhancer is essential for notochord and tail development

Project description:Genetic dissection of the mouse Brachyury locus identified a notochord enhancer and predicts additional control elements essential for trunk and tail development of the mouse embryo.

2021-11-26 | GSE179665 | GEO

A 37 kb region upstream of brachyury comprising a notochord enhancer is essential for notochord and tail development.

Project description:The node-streak border region comprising notochord progenitor cells (NPCs) at the posterior node and neuro-mesodermal progenitor cells (NMPs) in the adjacent epiblast is the prime organizing center for axial elongation in mouse embryos. The T-box transcription factor brachyury (T) is essential for both formation of the notochord and maintenance of NMPs, and thus is a key regulator of trunk and tail development. The T promoter controlling T expression in NMPs and nascent mesoderm has been characterized in detail; however, control elements for T expression in the notochord have not been identified yet. We have generated a series of deletion alleles by CRISPR/Cas9 genome editing in mESCs, and analyzed their effects in mutant mouse embryos. We identified a 37 kb region upstream of T that is essential for notochord function and tailbud outgrowth. Within that region, we discovered a T-binding enhancer required for notochord cell specification and differentiation. Our data reveal a complex regulatory landscape controlling cell type-specific expression and function of T in NMP/nascent mesoderm and node/notochord, allowing proper trunk and tail development.

| S-EPMC8722351 | biostudies-literature

Genome-wide identification of notochord enhancers comprising the regulatory landscape of the Brachyury (T) locus in mouse

Project description:The node and notochord are important signaling centers organizing dorso-ventral patterning of cells arising from neuro-mesodermal progenitors forming the embryonic body anlage. Due to the scarcity of notochordal progenitors and notochord cells, a comprehensive identification of regulatory elements driving notochord-specific gene expression has been lacking. Here we have used ATAC-seq analysis of FACS-purified notochordal cells from TS12-13 mouse embryos to identify 8921 putative enhancers of notochordal cells. In addition, we established a new model for generating notochordal cells in culture, and identified 3728 enhancers occupied by the essential notochordal regulators Brachyury (T) and/or Foxa2. We describe the regulatory landscape of the T locus comprising 8 putative enhancers occupied by these factors and confirmed the regulatory activity of 3 of these elements. Moreover, we characterized one new notochord enhancer, termed TNE2, in embryos. TNE2 complements the loss of TNE in the trunk notochord, and is essential for notochordal cell proliferation and differentiation in the tail. Our data demonstrate the essential role of Foxa2 in the choice of T expressing cells between the notochordal fate and the NMP/mesodermal trajectory

2023-10-31 | GSE235030 | GEO

Ectopic expression of the Brachyury transcription factor upregulates only a subset of notochord expressed genes

Project description:The key notochord transcription factor Brachyury was ectopically expressed in Ciona embryos under the control of the FoxAa cis-regulatory region (which drives expression in neural, endodermal and mesenchymal lineages in addition to notochord). Misexpression of Brachyury induced 925 genes compared to a control reporter plasmid (Bra>GFP). There was only modest overlap with a set of notochord-enriched genes previously identified by RNAseq of flow-sorted notochord cells, indicating that Brachyury is not a notochord master regulator gene as strictly defined.

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Genome-wide identification of notochord enhancers comprising the regulatory landscape of the Brachyury (T) locus in mouse

Project description:Genome-wide identification of notochord enhancers comprising the regulatory landscape of the Brachyury (T) locus in mouse

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Brachyury controls Ciona notochord fate as part of a feedforward network [IV]

Project description:The notochord is a defining feature of the chordates. The transcription factor Brachyury (Bra) is a key regulator of notochord fate but here we show that it is not a unitary master regulator in the model chordate Ciona. Ectopic Bra expression only partially reprograms other cell types to a notochord-like transcriptional profile and a subset of notochord-enriched genes are unaffected by CRISPR Bra disruption. We identify Foxa.a and Mnx as potential co-regulators and find that combinatorial cocktails are more effective at reprograming other cell types than Bra alone. We reassess the network relationships between Foxa.a, and other components of the notochord gene regulatory network and find that Foxa.a expression in the notochord is regulated by vegetal FGF signaling. It is a direct activator of Bra expression and has a binding motif that is significantly enriched in the regulatory regions of notochord-enriched genes. These and other results indicate that Bra and Foxa.a act together in a regulatory network dominated by positive feed-forward interactions, with neither being a classically-defined master regulator.er

2020-10-31 | GSE160547 | GEO

Brachyury controls Ciona notochord fate as part of a feedforward network [III]

2020-10-31 | GSE160546 | GEO

Brachyury controls Ciona notochord fate as part of a feedforward network [II]

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Brachyury controls Ciona notochord fate as part of a feedforward network [I]

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Brachyury ChIP-chip on Ciona intestinalis embryo (early-mid gastrula)

Project description:A genomic overview of in vivo binding of a transcription factor Brachyury in the ascidian gastrula embryo. Brachyury is known to be essential and sufficient for differentiation of the notochord. Keywords: ChIP-chip

2010-03-09 | GSE11925 | GEO

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