Wnt Signaling Mediates Self-Organization and Axis Formation in Embryoid Bodies
Open accessAbstract
Embryonic stem cells (ESCs) form descendants of all three germ layers when differentiated as aggregates, termed embryoid bodies. In vivo, differentiation of cells depends on signals and morphogen gradients that provide instructive and positional cues, but do such gradients exist in embryoid bodies? We report here the establishment of anteroposterior polarity and the formation of a primitive streak-like region in the embryoid body, dependent on local activation of the Wnt pathway. In this region, cells undergo an epithelial-to-mesenchymal transition and differentiate into mesendodermal progenitors. Exogenous Wnt3a protein posteriorizes the embryoid body, resulting in predominantly mesendodermal differentiation. Conversely, inhibiting Wnt signaling promotes anterior character and results in neurectodermal differentiation. The activation of Wnt signaling and primitive streak formation requires external signals but is self-reinforcing after initiation. Our findings show that the Wnt pathway mediates the local execution of a gastrulation-like process in the embryoid body, which displays an unexpected degree of self-organization.
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Inhibition of WNT signalling promotes anterior identity and enhances neurectodermal differentiation during early embryoid body differentiation, whereas activation posteriorizes the embryoid body and promotes mesoderm differentiation.
“Similar to its in vivo patterning, inhibition of WNT signalling promotes anterior identity and enhances neurectodermal differentiation during early-stage embryoid body differentiation, whereas activation of WNT signalling posteriorizes the embryoid body and promotes mesoderm differentiation34.”
From The use of brain organoids to investigate neural development and disease (2017) · cites this paper as [34]
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- Authors
- ten Berge, D., Koole, W., Fuerer, C., Fish, M., Eroglu, E., & Nusse, R.
- Affiliations
- Howard Hughes Medical Institute (US)
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2008-11
- Volume
- 3
- Issue
- 5
- Pages
- 508-518
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC2683270
- OpenAlex
- W2009393065
- Cited by
- 477
- References
- 79
- Citations by year
- 2026: 12 · 2025: 18 · 2024: 20 · 2023: 28 · 2022: 21 · 2021: 38 · 2020: 42 · 2019: 30 · 2018: 27 · 2017: 29 · 2016: 29 · 2015: 25 · 2014: 32 · 2013: 35 · 2012: 24
- FWCI
- 9.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1719 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of Diabetes and Digestive and Kidney Diseases (DK67834-01, R01DK067834)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Keywords
- Wnt signaling, embryoid bodies, embryonic stem cells, anteroposterior polarity, primitive streak, self-organization, epithelial-mesenchymal transition, Wnt3a, positional cues, morphogen gradients
- MeSH terms
- Animals, Cell Differentiation, Cells, Cultured, Cytoskeletal Proteins, Homeostasis, Mesoderm, Mice, Transgenic, Signal Transduction, Body Patterning, Embryonic Development, Wnt Proteins, Mice, Embryonic Stem Cells, Primitive Streak, Neural Plate, Axin Protein, Wnt3 Protein, Wnt3A Protein
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