Fig. 8: Graphical summary of the spatio-temporal signaling events during gastroesophageal histogenesis.

The illustration provides a comprehensive overview of the critical signaling events occurring during the evolution of gastroesophageal epithelia and fibroblasts at the GE-SCJ. In this depiction, we elucidate the differentiation pathways of esophagus and stomach epithelial cells, starting from their precursor cells expressing Sox11/Cldn6+ markers at embryonic stage 15. In the upper left portion of the panel (orange shades), precursor cells undergo differentiation into stratified squamous epithelial lineage cells (characterized by Trp63 + /Sox2 + /Krt5+ markers) as they progress through development, culminating in the formation of parabasal and terminally differentiated cells in the adult phase. Conversely, the upper right panel (blue shades) illustrates the evolution of stomach columnar epithelial cells (marked by Gata6 + /Krt8 + ). As development progresses, they organize into gland units with distinct epithelial regions such as the base, neck, and pit. In the lower panels, we observe the divergence in the distribution of esophageal (green shades) and stomach (magenta shades) stroma, featuring distinct subsets of fibroblasts with unique transcriptional signatures throughout development. Additionally, the regulation of key signaling pathways in the epithelia and fibroblasts, including WNT, BMP, EGF, FGF, PDGF, and TGF-ß pathways, with information on their signaling gradient established during gastroesophagus histogenesis are shown. C-FB indicates the combined fibroblast subclusters, as in Fig. 3b.