Lgr5 marks stem/progenitor cells contributing to epithelial and muscle development in the mouse esophagus

The existence and function of Lgr5⁺ cells within the developing esophagus remains unknown. Here, we document multiple discrete Lgr5⁺ populations in the developing mouse esophagus, predominantly within nascent epithelial and external muscle layers. Lgr5 expression initially emerges in the developing proximal embryonic epithelium, but progressively extends distally and persists within the distal epithelium of neonates. Fate mapping and ablation analyses reveal a long-term contribution of epithelial Lgr5⁺ cells to esophageal organogenesis. Additionally, Lgr5-expressing cells are present in the developing external muscle layer, particularly during the development of the striated component. Fate mapping reveals a significant contribution of these embryonic Lgr5⁺ cells to the adult muscle layer. Embryonic Lgr5⁺ epithelial cells are also found to be important for regulating epithelial development, serving as a key source of Wnt6, among other ligands, to promote epithelial cell proliferation and formation of epithelial layers. These findings significantly enhance our understanding of esophageal development and shed light on the involvement of Lgr5⁺ stem/progenitor cells during organogenesis. Importantly, this study lays the foundation for investigating esophageal diseases related to the Lgr5⁺ stem/progenitor cell pool.