Human trunk embryoids generated through co-development of notochord progenitors with bipotent neuromesodermal progenitors self-organize into structures with patterned anterior-posterior and dorsal-ventral body axes that recapitulate Carnegie stage 8-10 human embryonic trunk development, demonstrating that the notochord serves as a central organizing center for dorsal-ventral axis establishment through SHH signaling regulation and providing a platform for modeling human congenital diseases such as neural tube defects caused by VANGL1/2 mutations.

Human embryoid models enable mechanistic studies of development and disease. We generated trunk embryoids from human pluripotent stem cells that recapitulate posterior trunk formation at Carnegie stage (CS) 8-10, with patterned anterior-posterior (A-P) and dorsal-ventral (D-V) axes. These self-organizing structures comprise a ventral notochord, dorsal neural tube, floor plate and bilateral somites. Genetic and chemical perturbations of SHH signaling confirmed the notochord’s central role in D-V patterning. Moreover, VANGL1/2 loss-of-function mutations recapitulated mouse phenotypes, including axial truncation and somite segmentation failure. This model enables detailed study of key developmental events that underlie posterior trunk formation and provides a promising platform for human disease modeling.