Fig. 7. Epithelial cell plasticity drives endoderm formation.

a, Representative image of a mid-streak-stage embryo stained for Foxa2 and E-cadherin. b–e, Transverse sections through the epiblasts of wild-type mid- and late-streak-stage embryos immunostained for Foxa2 and Claudin7 (b), Foxa2, laminin and E-cadherin (c), Foxa2, Ezrin and E-cadherin (maximum projection) (d) and Foxa2, EBP50 and E-cadherin (e). f, Clustered heatmap showing the smoothed (sliding window of n = 100 cells) and scaled gene expression of polarity, cell adhesion, intermediate filaments (IF), basement membrane (BM) and metalloproteinases (MPs) in mesoderm (paraxial mesoderm, intermediate mesoderm, LPM and nascent endothelium), posterior epiblasts, transitory progenitors and definitive endoderm. The asterisks mark genes that have been confirmed by immunohistochemistry. g, Quadratic spline plot showing the expression of polarity and cell adhesion genes along diffusion pseudotime from epiblast to posterior epiblast to transitory progenitors to definitive endoderm. h, Schematic of endoderm formation by partial EMT. All samples were derived from biologically independent experiments. The images in a–d are representative of three embryos each. All shown confocal images are single planes of a z stack unless otherwise stated. Scale bars, 50 µm (insets, 10 µm).