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  2. Anteroposterior polarity and elongation in the absence of extra-embryonic tissues and of spatially localised signalling in gastruloids: mammalian embryonic organoids

Anteroposterior polarity and elongation in the absence of extra-embryonic tissues and of spatially localised signalling in gastruloids: mammalian embryonic organoids

  • Development. 2017 Nov 1;144(21):3894-3906. doi: 10.1242/dev.150391.
David A Turner 1 Mehmet Girgin 2 Luz Alonso-Crisostomo 3 Vikas Trivedi 3 Peter Baillie-Johnson 3 4 Cherise R Glodowski 3 Penelope C Hayward 3 Jérôme Collignon 5 Carsten Gustavsen 6 Palle Serup 6 Benjamin Steventon 3 Matthias P Lutolf 2 Alfonso Martinez Arias 1
Affiliations

Affiliations

  • 1 Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK dat40@cam.ac.uk ama11@cam.ac.uk.
  • 2 Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences and School of Engineering, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
  • 3 Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK.
  • 4 Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK.
  • 5 Université Paris-Diderot, CNRS, Institut Jacques Monod, 75013 Paris, France.
  • 6 Danish Stem Cell Center, University of Copenhagen, DK-2200 Copenhagen, Denmark.
Abstract

The establishment of the anteroposterior (AP) axis is a crucial step during animal embryo development. In mammals, genetic studies have shown that this process relies on signals spatiotemporally deployed in the extra-embryonic tissues that locate the position of the head and the onset of gastrulation, marked by T/Brachyury (T/Bra) at the posterior of the embryo. Here, we use gastruloids, mESC-based organoids, as a model system with which to study this process. We find that gastruloids localise T/Bra expression to one end and undergo elongation similar to the posterior region of the embryo, suggesting that they develop an AP axis. This process relies on precisely timed interactions between Wnt/β-catenin and Nodal signalling, whereas BMP signalling is dispensable. Additionally, polarised T/Bra expression occurs in the absence of extra-embryonic tissues or localised sources of signals. We suggest that the role of extra-embryonic tissues in the mammalian embryo might not be to induce the axes but to bias an intrinsic ability of the embryo to initially break symmetry. Furthermore, we suggest that Wnt signalling has a separable activity involved in the elongation of the axis.

Keywords

Axial organisation; Gastruloids; Organoids; Symmetry-breaking.

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