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Scheibner, K. ; Schirge, S. ; Burtscher, I. ; Büttner, M. ; Sterr, M. ; Yang, D.* ; Böttcher, A. ; Ansarullah ; Irmler, M. ; Beckers, J. ; Cernilogar, F.M.* ; Schotta, G.* ; Theis, F.J. ; Lickert, H.

Epithelial cell plasticity drives endoderm formation during gastrulation.

Nat. Cell Biol., DOI: 10.1038/s41556-021-00694-x (2021)
Publ. Version/Full Text DOI
Open Access Gold (Paid Option)
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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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords To-mesenchymal Transition; Transcription Factor; Definitive Endoderm; Beta-catenin; Gene-expression; Germ Layer; E-cadherin; Mouse; Snail; Metastasis
ISSN (print) / ISBN 1465-7392
e-ISSN 1476-4679
Publisher Nature Publishing Group
Publishing Place Heidelberger Platz 3, Berlin, 14197, Germany
Reviewing status Peer reviewed
Grants Deutsche Forschungsgemeinschaft (German Research Foundation)