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The transcription factor Pitx2 positions the embryonic axis and regulates twinning.

Angela Torlopp | Mohsin A F Khan | Nidia M M Oliveira | Ingrid Lekk | Luz Mayela Soto-Jiménez | Alona Sosinsky | Claudio D Stern
eLife | 2014

Embryonic polarity of invertebrates, amphibians and fish is specified largely by maternal determinants, which fixes cell fates early in development. In contrast, amniote embryos remain plastic and can form multiple individuals until gastrulation. How is their polarity determined? In the chick embryo, the earliest known factor is cVg1 (homologous to mammalian growth differentiation factor 1, GDF1), a transforming growth factor beta (TGFβ) signal expressed posteriorly before gastrulation. A molecular screen to find upstream regulators of cVg1 in normal embryos and in embryos manipulated to form twins now uncovers the transcription factor Pitx2 as a candidate. We show that Pitx2 is essential for axis formation, and that it acts as a direct regulator of cVg1 expression by binding to enhancers within neighbouring genes. Pitx2, Vg1/GDF1 and Nodal are also key actors in left-right asymmetry, suggesting that the same ancient polarity determination mechanism has been co-opted to different functions during evolution.

Pubmed ID: 25496870

Research resources used in this publication

None found

Antibodies used in this publication

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Associated grants

  • Agency: European Research Council, International
    Id: 249892
  • Agency: Biotechnology and Biological Sciences Research Council, United Kingdom
    Id: BB/C512753/1
  • Agency: Wellcome Trust, United Kingdom
    Id: WT083345MA

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Gene Regulation Databases (tool)

RRID:SCR_008033

In an effort to strongly support the collaborative nature of scientific research, BIOBASE offers academic and non-profit organizations free access to reduced functionality versions of their products. TRANSFAC Professional provides gene regulation analysis solutions, offering the most comprehensive collection of eukaryotic gene regulation data. The professional paid subscription gives customers access to up-to-date data and tools not available in the free version. The public databases currently available for academic and non-profit organizations are: * TRANSFAC: contains data on transcription factors, their experimentally-proven binding sites, and regulated genes. Its broad compilation of binding sites allows the derivation of positional weight matrices. * TRANSPATH: provides data about molecules participating in signal transduction pathways and the reactions they are involved in, resulting in a complex network of interconnected signaling components.TRANSPATH focuses on signaling cascades that change the activities of transcription factors and thus alter the gene expression profile of a given cell. * PathoDB: is a database on pathologically relevant mutated forms of transcription factors and their binding sites. It comprises numerous cases of defective transcription factors or mutated transcription factor binding sites, which are known to cause pathological defects. * S/MARt DB: presents data on scaffold or matrix attached regions (S/MARs) of eukaryotic genomes, as well as about the proteins that bind to them. S/MARs organize the chromatin in the form of functionally independent loop domains gained increasing support. Scaffold or Matrix Attached Regions (S/MARs) are genomic DNA sequences through which the chromatin is tightly attached to the proteinaceous scaffold of the nucleus. * TRANSCompel: is a database on composite regulatory elements affecting gene transcription in eukaryotes. Composite regulatory elements consist of two closely situated binding sites for distinct transcription factors, and provide cross-coupling of different signaling pathways. * PathoSign Public: is a database which collects information about defective cell signaling molecules causing human diseases. While constituting a useful data repository in itself, PathoSign is also aimed at being a foundational part of a platform for modeling human disease processes.

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Regulatory Sequence Analysis Tools (tool)

RRID:SCR_008560

THIS RESOURCE IS NO LONGER IN SERVICE. Documented on February 28,2023. Retrieve-ensembl-seq is included in the software suite regulatory sequence analysis tools (RSAT), allowing instant submission of retrieved sequences to further analysis tools. AVAILABILITY: retrieve-ensembl-seq is integrated in the RSAT suite: http://rsat.ulb.ac.be/rsat. Web site: http://rsat.ulb.ac.be/rsat/retrieve-ensembl-seq_form.cgi. Web services: http://rsat.ulb.ac.be/rsat/web_services/RSATWS.wsdl. Stand-alone distribution: freely available under an academic licence to download from the RSAT web site. The complete manual, a convenient tutorial and demos are available from the RSAT website. Additional help can be found on the RSAT public forum.

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ArrayExpress (tool)

RRID:SCR_002964

International functional genomics data collection generated from microarray or next-generation sequencing (NGS) platforms. Repository of functional genomics data supporting publications. Provides genes expression data for reuse to the research community where they can be queried and downloaded. Integrated with the Gene Expression Atlas and the sequence databases at the European Bioinformatics Institute. Contains a subset of curated and re-annotated Archive data which can be queried for individual gene expression under different biological conditions across experiments. Data collected to MIAME and MINSEQE standards. Data are submitted by users or are imported directly from the NCBI Gene Expression Omnibus.

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TRANSFAC (tool)

RRID:SCR_005620

Manually curated database of eukaryotic transcription factors, their genomic binding sites and DNA binding profiles. Used to predict potential transcription factor binding sites.

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LIMMA (tool)

RRID:SCR_010943

Software package for the analysis of gene expression microarray data, especially the use of linear models for analyzing designed experiments and the assessment of differential expression.

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