Symmetry breaking, germ layer specification and axial organisation in aggregates of mouse embryonic stem cells Journal Article


Authors: Van Den Brink, S. C.; Baillie-Johnson, P.; Balayo, T.; Hadjantonakis, A. K.; Nowotschin, S.; Turner, D. A.; Arias, A. M.
Article Title: Symmetry breaking, germ layer specification and axial organisation in aggregates of mouse embryonic stem cells
Abstract: Mouse embryonic stem cells (mESCs) are clonal populations derived from preimplantation mouse embryos that can be propagated in vitro and, when placed into blastocysts, contribute to all tissues of the embryo and integrate into the normal morphogenetic processes, i.e. they are pluripotent. However, although they can be steered to differentiate in vitro into all cell types of the organism, they cannot organise themselves into structures that resemble embryos. When aggregated into embryoid bodies they develop disorganised masses of different cell types with little spatial coherence. An exception to this rule is the emergence of retinas and anterior cortex-like structures under minimal culture conditions. These structures emerge from the cultures without any axial organisation. Here, we report that small aggregates of mESCs, of about 300 cells, self-organise into polarised structures that exhibit collective behaviours reminiscent of those that cells exhibit in early mouse embryos, including symmetry breaking, axial organisation, germ layer specification and cell behaviour, as well as axis elongation. The responses are signal specific and uncouple processes that in the embryo are tightly associated, such as specification of the anteroposterior axis and anterior neural development, or endoderm specification and axial elongation. We discuss the meaning and implications of these observations and the potential uses of these structures which, because of their behaviour, we suggest to call ‘gastruloids’.
Keywords: mouse; mesoderm; endoderm; gastrulation; symmetry breaking; pattern formation; neural ectoderm; axial elongation; live cell imaging; polarisation; self-organisation
Journal Title: Development
Volume: 141
Issue: 22
ISSN: 0950-1991
Publisher: Company of Biologists  
Date Published: 2014-11-01
Start Page: 4231
End Page: 4242
Language: English
DOI: 10.1242/dev.113001
PROVIDER: scopus
PUBMED: 25371360
PMCID: PMC4302915
DOI/URL:
Notes: Export Date: 1 December 2014 -- Source: Scopus
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