Advances in the development of organoid-based models of the trachea and esophagus

During organogenesis, the anterior foregut of the mammalian embryo undergoes morphological changes that give rise to the ventral trachea and the dorsal esophagus. Subsequently, the trachea on the ventral side functions as an air passage between the larynx and the bronchi, whereas the esophagus on the dorsal side develops a lumen to transport food from the pharynx to the stomach. Although mouse genetics has provided insights into various cell-cell interaction signals involved in the development of the trachea and esophagus, the exact mechanism remains elusive. Additionally, differences in tissue structure, cellular components, and developmental processes between species make it difficult to understand human development using animal models. However, human organoid technology has been developing rapidly over the past decade and is recognized as a technology that contributes to the elucidation of human organogenesis. This Review highlights our current understanding of the development and homeostasis of the trachea and esophagus. We also discuss the application of airway and esophageal organoids, which can help us better understand human organogenesis.