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Epithelial cell plasticity drives endoderm formation during gastrulation
- Source :
- Nat Cell Biol, Nature Cell Biology, Nat. Cell Biol. 23, 692-703 (2021)
- Publication Year :
- 2021
-
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.<br />Scheibner et al. demonstrate that, during gastrulation in the mouse, epithelial epiblast progenitors upregulate Foxa2 and form the definitive endoderm independently of a full EMT–MET cycle.
- Subjects :
- Mesoderm
Embryology
Embryonic stem cells
animal structures
Epithelial-Mesenchymal Transition
Time Factors
Cellular differentiation
Cell Plasticity
Gestational Age
Mice, Transgenic
Germ layer
Biology
Article
Cell Line
Mice
Endoderm formation
medicine
Animals
Cell lineage
Primitive streak
Endoderm
Gastrulation
Gene Expression Regulation, Developmental
Cell Differentiation
Epithelial Cells
Mouse Embryonic Stem Cells
Cell Biology
Publisher Correction
Cell biology
medicine.anatomical_structure
Blastocyst
Phenotype
Epiblast
embryonic structures
Hepatocyte Nuclear Factor 3-beta
Snail Family Transcription Factors
Subjects
Details
- ISSN :
- 14764679
- Volume :
- 23
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- Nature cell biology
- Accession number :
- edsair.doi.dedup.....2cb2dce3436ac2b2b5a565532990444f