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Anteroposterior polarity and elongation in the absence of extraembryonic tissues and spatially localised signalling in Gastruloids, mammalian embryonic organoids

Accepted version
Peer-reviewed

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Authors

Turner, DA 
Girgin, M 
Alonso-Crisostomo, L 
Baillie-Johnson, Peter  ORCID logo  https://orcid.org/0000-0003-2157-5017

Abstract

The establishment of the anteroposterior (AP) axis is a critical step during animal embryo development. In mammals, genetic studies have shown that this process relies on signals spatiotemporally deployed in the extraembryonic 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 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 extraembryonic tissues or localised sources of signals. We suggest that the role of extraembryonic 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.

Description

Keywords

Gastruloids, axial organisation, organoids, symmetry-breaking

Journal Title

Development

Conference Name

Journal ISSN

0950-1991
1477-9129

Volume Title

Publisher

The Company of Biologists
Sponsorship
Biotechnology and Biological Sciences Research Council (BB/M023370/1)
European Commission FP7 ERC Advanced Investigator Grants (AIG) (250316)
EPSRC (1359454)
National Centre for the Replacement Refinement and Reduction of Animals in Research (NC/P001467/1)
Wellcome Trust (109408/Z/15/Z)
BBSRC (BB/M023370/1), European Commission FP7 ERC Advanced Investigator Grants (AIG) (250316), EPSRC (1359454), NC3Rs (NC/P001467/1)
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