Recapitulating neural tube morphogenesis with human pluripotent stem cells

Abstract Neural tube morphogenesis is the first step in the formation of the nervous system, and tube defects are among the highest rate birth defects. However, it is not possible to study the dynamics of organ formation in humans. Animals differ from humans in key aspects, and in particular in the development of the nervous system. Conventional organoids are neither reproducible nor do they recapitulate the intricate anatomy of the neural tube. Here we describe a new protocol for recapitulating the intricate dynamics of neural tube morphogenesis using human stem cells. Our approach is reproducible, scalable, compatible with live imaging, genetic modifications, and drug screening. The protocol captures the early steps of neural development: pattering of the ectoderm into a neural plate and surface ectoderm, neural plate folding and closure, coverage by surface ectoderm, and neural crest cells differentiation and migration. This protocol opens up a way for further studies into the genetics and biophysics of the development of the human nervous system in health and disease.