Epithelial cell plasticity drives endoderm formation during gastrulation
Scheibner K, Schirge S, Burtscher I, Buettner M, Sterr M, Yang D, Boettcher A, Ansarullah , Irmler M, Beckers J, Cernilogar FM, Schotta G, Theis FJ, Lickert H (2021)
Publication Type: Journal article
Publication year: 2021
Journal
Book Volume: 23
Pages Range: 692-703
Journal Issue: 7
DOI: 10.1038/s41556-021-00694-x
Abstract
It is generally accepted that epiblast cells ingress into the primitive streak by epithelial-to-mesenchymal transition (EMT) to give rise to the mesoderm; however, it is less clear how the endoderm acquires an epithelial fate. Here, we used embryonic stem cell and mouse embryo knock‐in reporter systems to combine time-resolved lineage labelling with high-resolution single-cell transcriptomics. This allowed us to resolve the morphogenetic programs that segregate the mesoderm from the endoderm germ layer. Strikingly, while the mesoderm is formed by classical EMT, the endoderm is formed independent of the key EMT transcription factor Snail1 by mechanisms of epithelial cell plasticity. Importantly, forkhead box transcription factor A2 (Foxa2) acts as an epithelial gatekeeper and EMT suppressor to shield the endoderm from undergoing a mesenchymal transition. Altogether, these results not only establish the morphogenetic details of germ layer formation, but also have broader implications for stem cell differentiation and cancer metastasis.
Involved external institutions
Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich
Germany (DE)
Ludwig-Maximilians-Universität (LMU)
Germany (DE)
Memorial Sloan Kettering Cancer Center
United States (USA) (US)
Deutsches Zentrum für Diabetesforschung e.V. (DZD)
Germany (DE)
Germany (DE)
Ludwig-Maximilians-Universität (LMU)
Germany (DE)
Memorial Sloan Kettering Cancer Center
United States (USA) (US)
Deutsches Zentrum für Diabetesforschung e.V. (DZD)
Germany (DE)
How to cite
APA:
Scheibner, K., Schirge, S., Burtscher, I., Buettner, M., Sterr, M., Yang, D.,... Lickert, H. (2021). Epithelial cell plasticity drives endoderm formation during gastrulation. Nature Cell Biology, 23(7), 692-703. https://dx.doi.org/10.1038/s41556-021-00694-x
MLA:
Scheibner, Katharina, et al. "Epithelial cell plasticity drives endoderm formation during gastrulation." Nature Cell Biology 23.7 (2021): 692-703.
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