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
Affiliations
Angela Torlopp
Department of Cell and Developmental Biology, University College London, London, United Kingdom
Mohsin A F Khan
Department of Cell and Developmental Biology, University College London, London, United Kingdom
Nidia M M Oliveira
Department of Cell and Developmental Biology, University College London, London, United Kingdom
Ingrid Lekk
Department of Cell and Developmental Biology, University College London, London, United Kingdom
Luz Mayela Soto-Jiménez
Department of Cell and Developmental Biology, University College London, London, United Kingdom; Programa de Ciencias Genómicas, Universidad Nacional Autónoma de México, Morelos, Mexico
Alona Sosinsky
Institute of Structural and Molecular Biology, Birkbeck College, University of London, London, United Kingdom
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.