Epithelial cell plasticity drives endoderm formation during gastrulation

Katharina Scheibner, Silvia Schirge, Ingo Burtscher, Maren Büttner, Michael Sterr, Dapeng Yang, Anika Böttcher, Ansarullah, Martin Irmler, Johannes Beckers, Filippo M. Cernilogar, Gunnar Schotta, Fabian J. Theis, Heiko Lickert

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

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.

Original languageEnglish
Pages (from-to)692-703
Number of pages12
JournalNature Cell Biology
Volume23
Issue number7
DOIs
StatePublished - Jul 2021

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