title: The transcription factor Pitx2 positions the embryonic axis and regulates twinning.
abstract: 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.
authors.affiliation: Department of Cell and Developmental Biology, University College London, London, United Kingdom.
authors.forename: Angela
authors.initials: A
authors.lastname: Torlopp
authors.affiliation: Department of Cell and Developmental Biology, University College London, London, United Kingdom.
authors.forename: Mohsin A F
authors.initials: MA
authors.lastname: Khan
authors.affiliation: Department of Cell and Developmental Biology, University College London, London, United Kingdom.
authors.forename: Nidia M M
authors.initials: NM
authors.lastname: Oliveira
authors.affiliation: Department of Cell and Developmental Biology, University College London, London, United Kingdom.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Lekk
authors.affiliation: Department of Cell and Developmental Biology, University College London, London, United Kingdom.
authors.forename: Luz Mayela
authors.initials: LM
authors.lastname: Soto-Jiménez
authors.affiliation: Institute of Structural and Molecular Biology, Birkbeck College, University of London, London, United Kingdom.
authors.forename: Alona
authors.initials: A
authors.lastname: Sosinsky
authors.affiliation: Department of Cell and Developmental Biology, University College London, London, United Kingdom.
authors.forename: Claudio D
authors.initials: CD
authors.lastname: Stern
mesh_terms: D000818:Animals; D030161:Avian Proteins / Q000378:metabolism; D002642:Chick Embryo; D047369:Chromatin Immunoprecipitation; D019295:Computational Biology; D047108:Embryonic Development / Q000235:genetics*; D004742:Enhancer Elements, Genetic / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006657:Histones / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D017403:In Situ Hybridization; D008098:Litter Size / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011485:Protein Binding / Q000235:genetics; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000097577:Homeobox Protein PITX2
chemical_list: D030161:Avian Proteins; D006657:Histones; D018398:Homeodomain Proteins; D014157:Transcription Factors; D000097577:Homeobox Protein PITX2
keywords: chicken; developmental biology; embryo polarity; embryonic axis; gastrulation; primitive streak; stem cells