Anteroposterior polarity and elongation in the absence of extraembryonic tissues and of spatially localised signalling in gastruloids: Mammalian embryonic organoids

David A. Turner; Mehmet Girgin; Luz Alonso-Crisostomo; Vikas Trivedi; Peter Baillie-Johnson; Cherise R. Glodowski; Penelope C. Hayward; Jérôme Collignon; Carsten Gustavsen; Palle Serup; Benjamin Steventon; Matthias P. Lutolf; Alfonso Martinez Arias

doi:10.1242/dev.150391

Anteroposterior polarity and elongation in the absence of extraembryonic tissues and of spatially localised signalling in gastruloids: Mammalian embryonic organoids

David A. Turner^*, Mehmet Girgin, Luz Alonso-Crisostomo, Vikas Trivedi, Peter Baillie-Johnson, Cherise R. Glodowski, Penelope C. Hayward, Jérôme Collignon, Carsten Gustavsen, Palle Serup, Benjamin Steventon, Matthias P. Lutolf, Alfonso Martinez Arias

^*Corresponding author for this work

Developmental biology of the pancreas Lab

74 Citations (Scopus)

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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.

Original language	English
Journal	Development (Cambridge)
Volume	144
Issue number	21
Pages (from-to)	3894-3906
Number of pages	13
ISSN	0950-1991
DOIs	https://doi.org/10.1242/dev.150391
Publication status	Published - Nov 2017

Keywords

Axial organisation
Gastruloids
Organoids
Symmetry-breaking

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Turner, D. A., Girgin, M., Alonso-Crisostomo, L., Trivedi, V., Baillie-Johnson, P., Glodowski, C. R., Hayward, P. C., Collignon, J., Gustavsen, C., Serup, P., Steventon, B., Lutolf, M. P., & Arias, A. M. (2017). Anteroposterior polarity and elongation in the absence of extraembryonic tissues and of spatially localised signalling in gastruloids: Mammalian embryonic organoids. Development (Cambridge), 144(21), 3894-3906. https://doi.org/10.1242/dev.150391

Anteroposterior polarity and elongation in the absence of extraembryonic tissues and of spatially localised signalling in gastruloids: Mammalian embryonic organoids. / Turner, David A.; Girgin, Mehmet; Alonso-Crisostomo, Luz et al.
In: Development (Cambridge), Vol. 144, No. 21, 11.2017, p. 3894-3906.

Research output: Contribution to journal › Journal article › Research › peer-review

Turner, DA, Girgin, M, Alonso-Crisostomo, L, Trivedi, V, Baillie-Johnson, P, Glodowski, CR, Hayward, PC, Collignon, J, Gustavsen, C, Serup, P, Steventon, B, Lutolf, MP & Arias, AM 2017, 'Anteroposterior polarity and elongation in the absence of extraembryonic tissues and of spatially localised signalling in gastruloids: Mammalian embryonic organoids', Development (Cambridge), vol. 144, no. 21, pp. 3894-3906. https://doi.org/10.1242/dev.150391

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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.",

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AU - Trivedi, Vikas

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AU - Hayward, Penelope C.

AU - Collignon, Jérôme

AU - Gustavsen, Carsten

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AU - Lutolf, Matthias P.

AU - Arias, Alfonso Martinez

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AB - 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.

KW - Axial organisation

KW - Gastruloids

KW - Organoids

KW - Symmetry-breaking

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DO - 10.1242/dev.150391

M3 - Journal article

C2 - 28951435

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JO - Development (Cambridge)

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ER -

Anteroposterior polarity and elongation in the absence of extraembryonic tissues and of spatially localised signalling in gastruloids: Mammalian embryonic organoids

Abstract

Keywords

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