Vertebrate endoderm development.

The endoderm forms the innermost layer of the embryonic gut tube. It gives rise to the epithelial and glandular components of many internal organs, including those of the digestive and respiratory systems. Endodermal organs have essential physiological processes such as nutrient absorption, respiration, detoxification and endocrine regulation. Over the past two decades, work in vertebrate embryos and human pluripotent stem cell models has defined the mechanisms that govern endoderm formation, regionalization and organogenesis. These processes are driven by conserved cell signaling pathways acting in concert with lineage-specific transcription factors to establish and refine endodermal cell identity. Interactions between endoderm and adjacent mesoderm further guide tissue morphogenesis and organ-specific differentiation. Insights from these studies not only reveal fundamental principles of development, but also inform the origins of congenital disorders and advance efforts to engineer functional human tissues in vitro for disease modeling and regenerative medicine.